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Phase III Efficacy, Safety, and Tolerability Study of HYQVIA/HyQvia and GAMMAGARD LIQUID/KIOVIG in CIDP

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ClinicalTrials.gov Identifier: NCT02549170
Recruitment Status : Recruiting
First Posted : September 15, 2015
Last Update Posted : August 30, 2019
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
This is a Phase III, prospective, multicenter study with two study parts (epochs) to evaluate the efficacy, safety, and tolerability of HYQVIA/HyQvia (IGI, 10% with recombinant human hyaluronidase (rHuPH20) administered subcutaneously) for maintenance therapy to prevent relapse (Epoch 1) and GAMMAGARD LIQUID/KIOVIG (immunoglobulin G intravenous (IGIV) 10% administered intravenously) for the treatment of CIDP (Epoch 2). This study will enroll adult subjects with a confirmed diagnosis of CIDP and who have remained on a stable dosing regimen (monthly equivalent dose of 0.4 to 2.4 g/kg body weight (BW) with a dosing interval of 2 to 6 weeks) of IGIV therapy for at least 3 months prior to screening. In this double-blind, placebo-controlled phase of the study (Epoch 1), eligible subjects will be randomized in a 1:1 ratio to receive either HYQVIA/HyQvia or 0.25% albumin placebo solution with rHuPH20 every two, three, or four weeks in a double-blind fashion for a period of 6 months or until relapse. Subjects who relapse during Epoch 1 will enter Epoch 2 to receive IGIV treatment for a period of 6 months.

Condition or disease Intervention/treatment Phase
Chronic Inflammatory Demyelinating Polyradiculoneuropathy Biological: HYQVIA Biological: 0.25% albumin placebo solution with rHuPH20 Biological: IGIV Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 232 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Immune Globulin Infusion 10% (Human) With Recombinant Human Hyaluronidase (HYQVIA/HyQvia) and Immune Globulin Infusion (Human), 10% (GAMMAGARD LIQUID/KIOVIG) for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Actual Study Start Date : April 29, 2016
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Epoch 1: HYQVIA/HyQvia
Participants will receive SC HYQVIA/HyQvia at a dose of 80 Unit per gram (U/g) immunoglobulin (IgG) which will be same as the participants pre-randomization monthly equivalent IgG dose (or at matching infusion volume for participants in the placebo group) when administered at a dosing frequency of every 2, 3, or 4 weeks for 6 months or until relapse.
Biological: HYQVIA
Participants will receive subcutaneous (SC) HYQVIA/HyQvia which contains both Immune Globulin Infusion 10% (Human) (IGI, 10%) and recombinant human hyaluronidase (rHuPH20).
Other Names:
  • 10%) with recombinant human hyaluronidase (rHuPH20)
  • Immune Globulin Infusion 10% (Human) (IGI
  • IGI
  • 10% with rHuPH20

Placebo Comparator: Epoch 1: Placebo with rHuPH20
Participants will receive sequential 0.25% albumin placebo with rHuPH20 at a dose of 80U/g IgG subcutaneously for 6 months or until relapse. Dosing regimen for placebo treatment will be the same as the participant's pre-randomization monthly equivalent IgG infusion volume when administered every 2, 3, or 4 weeks.
Biological: 0.25% albumin placebo solution with rHuPH20
Participants will receive placebo solution (0.25% human albumin in Lactated Ringer's solution) and rHuPH20.

Experimental: Epoch 2: IGIV
Participants will recieve an induction dose of 2 Gram per kilogram (g/kg) Intravenous immunoglobulin G (IGIV), followed by maintenance infusions at the same monthly dose as the participant's pre-randomization IgG dose, every 3 weeks for 6 months or until relapse.
Biological: IGIV
Participants will receive GAMMAGARD LIQUID/KIOVIG (all participants with the exception of those at US sites) or GAMUNEX®-C (participants at US sites only).
Other Names:
  • Immune Globulin Infusion (Human)
  • Intravenous immunoglobulin G
  • 10% (GAMMAGARD LIQUID/KIOVIG)
  • Approved IGIV product for US sites
  • GAMMAGARD LIQUID




Primary Outcome Measures :
  1. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Pre-SC Baseline Week 1 [ Time Frame: Pre-SC Baseline (Week 1) ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of greater than or equal to (>=)1 point relative to the pre- subcutaneous (SC) treatment baseline score in 2 consecutive adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  2. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 5 [ Time Frame: Week 5 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  3. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 9 [ Time Frame: Week 9 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  4. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 13 [ Time Frame: Week 13 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  5. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 15 [ Time Frame: Week 15 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  6. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 19 [ Time Frame: Week 19 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  7. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 23 [ Time Frame: Week 23 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  8. Epoch 1: Relapse Rate on Every 2 Weeks Dosing Regimen (Q2W) at Week 27 (End of Epoch 1 Treatment [EOE1T])/Unscheduled relapse visit assessment (UV)/Early Termination (ET) [ Time Frame: Week 27 (EOET1)/UV/ET ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  9. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Pre-SC Baseline [ Time Frame: Pre-SC Baseline ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  10. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 5 [ Time Frame: Week 5 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  11. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 8 [ Time Frame: Week 8 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  12. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 11 [ Time Frame: Week 11 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  13. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 14 [ Time Frame: Week 14 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  14. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 17 [ Time Frame: Week 17 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  15. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 20 [ Time Frame: Week 20 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  16. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 23 [ Time Frame: Week 23 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  17. Epoch 1: Relapse Rate on Every 3 Weeks Dosing Regimen (Q3W) at Week 26 (EOE1T)/Unscheduled relapse visit assessment (UV)/Early Termination (ET) [ Time Frame: Week 26 (EOE1T)/UV/ET ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  18. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Pre-SC Baseline [ Time Frame: Pre-SC Baseline ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  19. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 5 [ Time Frame: Week 5 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  20. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 8 [ Time Frame: Week 8 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  21. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 12 [ Time Frame: Week 12 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  22. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 16 [ Time Frame: Week 16 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  23. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 20 [ Time Frame: Week 20 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  24. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 24 [ Time Frame: Week 24 ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  25. Epoch 1: Relapse Rate on Every 4 Weeks Dosing Regimen (Q4W) at Week 28 (EOET1)/Unscheduled relapse visit assessment (UV)/Early Termination (ET) [ Time Frame: Week 28 (EOET1)/UV/ET ]
    Relapse rate is defined as proportion of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

  26. Epoch 2: Responder Rate on Every 3 Weeks Dosing Regimen at Pre-Baseline (Week 1) [ Time Frame: Pre-IV Baseline (Week 1) ]
    Responder rate is defined as clinically meaningful improvement in functional ability defined as a decrease of >=1 point in the adjusted INCAT disability score at the completion of the intravenous (IV) treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.

  27. Epoch 2: Responder Rate on Every 3 Weeks Dosing Regimen up to 6 Months (End of Epoch 2 Treatment [EOE2T])/Unscheduled visit assessment (UV)/Early Termination [ Time Frame: Up to 6 Months/UV/ET ]
    Responder rate is defined as clinically meaningful improvement in functional ability defined as a decrease of >=1 point in the adjusted INCAT disability score at the completion of the intravenous (IV) treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.


Secondary Outcome Measures :
  1. Epoch 1: Time to Relapse [ Time Frame: Throughout Epoch 1, up to 6 months ]
    Time to relapse is defined as time from the date of the first SC administration of HYQVIA/HyQvia or placebo with rHuPH20 to the date of relapse.

  2. Epoch 1: Change From Pre-Subcutaneous (SC) Treatment Baseline in Rasch-built Overall Disability Scale (R-ODS) Score [ Time Frame: Pre-subcutaneous (SC) treatment baseline, then weekly through Epoch 1 (up to 6 months); Unscheduled relapse visit assessment; & if early termination occurs. ]
    The Rasch-Built Overall Disability Scale (R-ODS) is a participant self-reported, linearly-weighted overall disability scale that was specifically designed to capture activity and social participation limitations in participant with immune-mediated peripheral neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The R-ODS is comprised of 24 items for which participants are asked to rate their functioning (ie, no difficulty, some difficulty, or could not do) related to a variety of everyday tasks at the moment of completion.

  3. Epoch 1: Number of Participants Experiencing Any Treatment-Emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  4. Epoch 1: Number of Participants Experiencing Causally Related Serious And/or Non-Serious Adverse Events (SAEs And/or AEs) [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  5. Epoch 1: Number of Participants With Serious And/Or Non-serious Adverse Reactions (ARs) Plus Suspected ARs [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  6. Epoch 1: Number of Infusions Associated with Treatment-emergent Serious And/Or Non-serious Adverse Events (SAEs And/Or AEs), Regardless of Causality [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  7. Epoch 1: Number of Infusions Associated with Causally Related Serious And/Or Non-serious Adverse Events (SAEs And/Or AEs) [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  8. Epoch 1: Number of Infusions Temporally Associated with Adverse Events (AEs) [ Time Frame: During an infusion or within 72 hours after completion of an infusion ]
    AEs occurring during an infusion or within 72 hours after completion of an infusion. An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  9. Epoch 1: Number of Infusions Associated with Serious And/Or Non-serious Adverse Reactions (ARs) plus Suspected ARs [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  10. Epoch 1: Number of Infusions Associated with Treatment-emergent Systemic Adverse Events (AEs) [ Time Frame: Throughout Epoch 1, up to 6 months ]
    A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments.

  11. Epoch 1: Number of Infusions Associated with Treatment-emergent Local Infusion Site Reactions [ Time Frame: Throughout Epoch 1, up to 6 months ]
  12. Epoch 1: Number of Infusions for Which the Infusion Rate Was Reduced And/Or the Infusion Was Interrupted or Stopped Due to Intolerability And/Or Adverse Events (AEs) [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  13. Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  14. Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events per Participant [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  15. Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events per Participant-year [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  16. Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  17. Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Participant [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  18. Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events per Participant-year [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  19. Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected Ars, Expressed as Number of Events per Infusion [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  20. Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per Participant [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  21. Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per Participant-Year [ Time Frame: Throughout Epoch 1, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  22. Epoch 1: Number of Participants Who Develop Binding And/Or Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20) [ Time Frame: Throughout Epoch 1, up to 6 months ]
  23. Epoch 2: Number of Participants Experiencing Any Treatment-emergent Serious And/Or Non-serious Adverse Events (SAEs And/Or AEs), Regardless of Causality [ Time Frame: Throughout Epoch 2, up to 6 months ]
  24. Epoch 2: Number of Participants Experiencing Causally Related Serious And/Or Non-serious Adverse Events (SAEs And/Or AEs) [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  25. Epoch 2: Number of Participants with Serious And/Or Non-serious Adverse Reactions (ARs) plus Suspected ARs [ Time Frame: Throughout Epoch 2, up to 6 months ]
    A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria. An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  26. Epoch 2: Number of Infusions Associated with Treatment-emergent Serious And/Or Non-serious Adverse Events (SAEs And/Or AEs), Regardless of Causality [ Time Frame: Throughout Epoch 2, up to 6 months ]
    A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria. An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  27. Epoch 2: Number of Infusions Associated With Causally Related Serious And/Or Non-serious Adverse Events (SAEs And/Or AEs) [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.

  28. Epoch 2: Number of Infusions Temporally Associated with Adverse Events (AEs) [ Time Frame: During an infusion or within 72 hours after completion of an infusion ]
    AEs occurring during an infusion or within 72 hours after completion of an infusion. An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  29. Epoch 2: Number of Infusions Associated with Serious And/Or Non-serious Adverse Reactions (ARs) plus Suspected ARs [ Time Frame: Throughout Epoch 2, up to 6 months ]
    A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria. An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  30. Epoch 2: Number of Infusions Associated with Treatment-emergent Systemic Adverse Events (AEs) [ Time Frame: Throughout Epoch 2, up to 6 months ]
    A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments.

  31. Epoch 2: Number of Infusions Associated with Treatment-emergent Local Infusion Site Reactions [ Time Frame: Throughout Epoch 2, up to 6 months ]
  32. Epoch 2: Number of Infusions for Which the Infusion Rate Was Reduced And/Or the Infusion Was Interrupted or Stopped Due to Intolerability And/Or Adverse Events (AEs) [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  33. Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  34. Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  35. Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant-year [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  36. Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  37. Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  38. Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-Year [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.

  39. Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected Ars, Expressed as Number of Events Per Infusion [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  40. Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events Per Participant [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  41. Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events Per Participant-Year [ Time Frame: Throughout Epoch 2, up to 6 months ]
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate.

  42. Epoch 1: Proportion of Participants Who Experience a Worsening of Functional Disability [ Time Frame: Throughout Epoch 1, up to 6 months ]
    Defined as one or more of the following: an increase of >=1 point relative to the pre-subcutaneous (SC) treatment baseline score in 2 consecutive adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT) scores; who experience chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) worsening (defined as a >=8 kilo Pascal (kPa) decrease in the hand grip strength in the more affected hand); >=4 points decrease in Rasch-built Overall Disability Scale (R-ODS) relative to the pre-SC treatment baseline score (at the time of withdrawal from the SC treatment period).

  43. Epoch 2: Proportion of Participants With Clinically Meaningful Improvement in Functional Ability [ Time Frame: Throughout Epoch 2, up to 6 months ]
    Defined as one or more of the following: a decrease of >=1 point in the adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT) score at 2 consecutive time points; who experience chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) improvement (defined as ≥8 kilo Pascal (kPa) increase in hand grip strength in the more affected hand; >=4 points increase in Rasch-built Overall Disability Scale (R-ODS)) at the completion of the intravenous (IV) treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females of age greater than or equal to (>=)18 years old at the time of screening.
  2. Documented diagnosis of definite or probable Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (focal atypical CIDP and pure sensory atypical CIDP will be excluded) consistent with EFNS/PNS 2010 criteria (European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy, 2010). Fulfillment of electrodiagnostic criteria must be confirmed by an independent qualified/experienced central reader.
  3. Participant has responded to IgG treatment in the past (partial or complete resolution of neurological symptoms and deficits), and must currently be on stable doses of IGIV treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 gram per kilogram (g/kg) BW (inclusive) administered intravenously for at least 12 weeks prior to screening. The dosing interval of IGIV treatment must be between 2 and 6 weeks (inclusive). Variations in the dosing interval of up to ± 7 days or monthly dose amount of up to ± 20% between participant's pre-study Immunoglobulin G (IgG) infusions are within acceptable limits.
  4. INCAT disability score between 0 and 7 (inclusive). Participants with INCAT scores of 0, 1 (whether from upper or lower extremities), or 2 (if at least 1 point is from an upper extremity) at screening and/or baseline will be required to have a history of significant disability as defined by an INCAT disability score of 2 (must be exclusively from the lower extremities) or greater documented in the medical record. Participants will be eligible if one of the below eligibility criteria are met:

    1. Screening and Baseline INCAT disability score of between 3 and 7 inclusive.
    2. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities).
    3. Screening and/or Baseline INCAT disability score of 2 (both points are not from lower extremities) AND has at least a score of 2 or greater documented in the medical record prior to screening. If a score was greater than 2 documented in the medical record prior to screening at least 2 points must be from lower extremities.
    4. Screening and/or Baseline INCAT disability score of 0 or 1 AND has at least a score of 2 or greater (both from lower extremities) documented in the medical record prior to screening, at least 2 points must be from lower extremities.
  5. If female of childbearing potential, the participant must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the study and for at least 30 days after the last administration of investigational product (IP).
  6. Participant is willing and able to sign an Informed Consent Form (ICF).
  7. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

  1. Participants with Focal atypical CIDP or pure sensory atypical CIDP.
  2. Any neuropathy of other causes, including:

    1. Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN) (Charcot-Marie-Tooth [CMT] disease), and hereditary sensory and autonomic neuropathies (HSANs).
    2. Neuropathies secondary to infections, disorders, or systemic diseases such as Borrelia burgdorferi infection (Lyme disease), diphtheria, systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly, endocrinopathy,M-protein, and skin changes) syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy, lymphoma, and amyloidosisc.Multifocal motor neuropathy (MMN).
    3. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).
    4. Multifocal motor neuropathy (MMN).
    5. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy.
  3. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein.
  4. Prominent sphincter disturbance.
  5. Central demyelinating disorders (eg, multiple sclerosis).
  6. Any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or may interfere with assessment of CIDP or outcome measures (eg, arthritis, stroke, Parkinson's disease, and diabetic peripheral neuropathy) (Participants with clinically diagnosed diabetes mellitus who do not have diabetic peripheral neuropathy, who have adequate glycemic control with Hemoglobin A1C; also known as glycosylated or glycated hemoglobin (HbA1C) of less than (<) 7.5% at screening, and who agree to maintain adequate glycemic control during the study are allowed).
  7. Congestive heart failure (New York Heart Association (NYHA) Class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension (ie, diastolic blood pressure greater than (>)100 millimeter of mercury (mmHg) and/or systolic blood pressure >160 mmHg).
  8. History of deep vein thrombosis or thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) in the past 12 months.
  9. Condition(s) which could alter protein catabolism and/or IgG utilization (eg, protein-losing enteropathies, nephrotic syndrome).
  10. Known history of chronic kidney disease, or glomerular filtration rate (GFR) of <60 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) estimated based on CKD-EPI equation (Levey et al., 2009) at the time of screening.
  11. Participant with active malignancy requiring chemotherapy and/or radiotherapy, or history of malignancy with less than 2 years of complete remission prior to screening. Exceptions are: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment.
  12. Clinically significant anemia or hemoglobin (Hgb) level of less than (<) 10.0 grams per deciliter (g/dL) at screening.
  13. Hypersensitivity or adverse reactions (AR's) (eg, urticaria, breathing difficulty, severe hypotension, or anaphylaxis) to human blood products such as human IgG, albumin, or other blood components.
  14. Known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or animal origin (such as bee or wasp venom).
  15. Known history of or immunoglobulin A (IgA) deficiency (<8 milligram per deciliter [mg/dL]) at screening.
  16. Abnormal laboratory values at screening:

    1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN)
    2. Platelet count <100,000 cells per micro liter (cells/µL).
    3. Absolute neutrophil count (ANC) <1000 cells/µL.
  17. Ongoing/active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Type 1/2 infection.
  18. The participant has received or is currently receiving treatment with immunomodulatory/ immunosuppressive agents within 6 months prior to screening.
  19. Participant has received or is currently receiving treatment with corticosteroids dose within 8 weeks prior to screening, regardless of indication.
  20. Participant has undergone plasma exchange (PE) within 3 months prior to screening.
  21. The participant has any disorder or condition that in the investigator's judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study.
  22. The participant is nursing or intends to begin nursing during the course of the study.
  23. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment, or is scheduled to participate in another clinical study (with the exception of the HYQVIA/HyQvia extension study in CIDP) involving an IP or investigational device during the course of this study.
  24. The participant is a family member or employee of the investigator.
  25. Participants with acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put participants at risk of develop thrombotic events. Examples include:

    a. Hereditary Thrombophilias i.Factor V Leiden mutation. ii.Prothrombin 20210A mutation. iii.Protein C deficiency. iv.Protein S deficiency. v.Antithrombin deficiency. b. Acquired thrombophilias i. Antiphospholipid antibody syndrome. ii. Activated protein C Resistance acquired. iii. Homocystinemia.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02549170


Contacts
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Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

  Show 77 Study Locations
Sponsors and Collaborators
Baxalta now part of Shire
Baxalta Innovations GmbH, now part of Shire
Investigators
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Study Director: Study Director Shire

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Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02549170     History of Changes
Other Study ID Numbers: 161403
2014-005496-87 ( EudraCT Number )
First Posted: September 15, 2015    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shire ( Baxalta now part of Shire ):
Autoimmune Diseases
Polyneuropathies
Nervous System Diseases
Peripheral Nervous System Diseases
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Immunoglobulins
Immune System Diseases
Demyelinating Diseases
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Neuromuscular Diseases
Additional relevant MeSH terms:
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Polyradiculoneuropathy
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs