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A Study to Evaluate the Efficacy and Safety of Efgartigimod PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia (ADVANCE SC)

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ClinicalTrials.gov Identifier: NCT04687072
Recruitment Status : Recruiting
First Posted : December 29, 2020
Last Update Posted : October 14, 2021
Sponsor:
Information provided by (Responsible Party):
argenx

Brief Summary:
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group trial to evaluate the efficacy, safety, and effect on QoL/PRO of efgartigimod PH20 SC treatment in adult patients with primary ITP.

Condition or disease Intervention/treatment Phase
Primary Immune Thrombocytopenia Biological: Efgartigimod PH20 SC Other: Placebo PH20 SC Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and the Safety of Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia
Actual Study Start Date : December 11, 2020
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2022


Arm Intervention/treatment
Experimental: Efgartigimod PH20 SC
Patients receiving efgartigimod PH20 SC treatment
Biological: Efgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC
Other Name: ARGX-113 PH20 SC

Placebo Comparator: Placebo PH20 SC
Patients receiving placebo PH20 SC treatment
Other: Placebo PH20 SC
Subcutaneous injection with placebo PH20 SC




Primary Outcome Measures :
  1. Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of ≥50×10E9/L for at least 4 of the 6 visits between week 19 and week 24 of the trial [ Time Frame: Up to 5 weeks (between week 19 -24) ]

Secondary Outcome Measures :
  1. Extent of disease control defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥50×10E9/L in the chronic ITP population [ Time Frame: Up to 24 weeks ]
  2. Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count response defined as achieving platelet counts of ≥50×10E9/L for at least 4 of the 6 visits between week 19 and week 24 [ Time Frame: Up to 5 weeks (between week 19-24) ]
  3. Proportion of patients in the overall population achieving platelet counts of ≥50×10E9/L for at least 6 of the 8 visits between week 17 and 24 of the trial [ Time Frame: Up to 7 weeks (between week 17-24) ]
  4. Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of ≥50×10E9/L on at least 4 occasions at any time during the 24-week treatment period [ Time Frame: Up to 24 weeks ]
  5. Extent of disease control defined as the number of cumulative weeks until week 12 with platelet counts of ≥50×10E9/L in the overall population [ Time Frame: Up to 12 weeks ]
  6. Proportion of patients in the overall population with overall platelet response defined as achieving a platelet count of ≥50×10E9/L on at least 4 occasions at any time until week 12 [ Time Frame: Up to 12 weeks ]
  7. Mean change from baseline in platelet count at each visit in the overall population [ Time Frame: Up to 35 weeks ]
  8. Time to response defined as the time to achieve 2 consecutive platelet counts of ≥50×10E9/L in the overall population [ Time Frame: Up to 35 weeks ]
  9. The number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10E9/L and ≥20×10E9/L above baseline in the overall population [ Time Frame: Up to 24 weeks ]
  10. In patients with baseline platelet count of <15×10E9/L, the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10E9/L and ≥20×10E9/L above baseline in the overall population [ Time Frame: Up to 24 weeks ]
  11. Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population [ Time Frame: Up to 35 weeks ]
  12. Severity of the World Health Organization (WHO)-classified bleeding events in the overall population [ Time Frame: Up to 35 weeks ]
  13. Incidence and severity of AEs, AEs of special interest (AESIs), and SAEs in the overall population [ Time Frame: Up to 35 weeks ]
  14. Vital sign measurement: blood pressure in the overall population [ Time Frame: Up to 35 weeks ]
  15. ECG: PR, QT and QRS interval in the overall population [ Time Frame: Up to 35 weeks ]
  16. Laboratory assessments: blood and urine analysis in the overall population [ Time Frame: Up to 35 weeks ]
  17. Rate of receipt of rescue therapy (rescue per patient per month) in the overall population [ Time Frame: Up to 35 weeks ]
  18. Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have increased at week 12 or later in the overall population [ Time Frame: Up to 23 weeks (between week 12-35) ]
  19. Change from baseline in PRO (Functional Assessment of Chronic Illness Therapy Fatigue Scale [FACIT-Fatigue] at planned visits in the overall population [ Time Frame: Up to 24 weeks ]
  20. Change from baseline in PRO Functional Assessment of Cancer Therapy questionnaire-Th6 [Fact-Th6]) at planned visits in the overall population [ Time Frame: Up to 24 weeks ]
  21. Change from baseline in PRO QoL (Short Form-36 [SF-36]) at planned visits in the overall population [ Time Frame: Up to 24 weeks ]
  22. Incidence of antibodies to efgartigimod and/or rHuPH20 in the overall population [ Time Frame: Up to 35 weeks ]
  23. Prevalence of antibodies to efgartigimod and/or rHuPH20 in the overall population [ Time Frame: Up to 35 weeks ]
  24. Titers of antibodies to efgartigimod and/or rHuPH20 in the overall population [ Time Frame: Up to 35 weeks ]
  25. Presence of neutralizing antibodies (NAb) against efgartigimod and/or rHuPH20, and titers of NAb against efgartigimod and/or rHuPH20 in the overall population [ Time Frame: Up to 35 weeks ]
  26. Serum efgartigimod concentration observed predose (Ctrough) in the overall population [ Time Frame: Up to 35 weeks ]
  27. Pharmacodynamics markers: total IgG and antiplatelet antibody levels in the overall population [ Time Frame: Up to 35 weeks ]


Information from the National Library of Medicine

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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:

  • Ability to understand the requirements of the trial and provide written informed consent (including consent for the use and disclosure of research-related health information), willing and able to comply with the trial protocol procedures (including attending the required trial visits)
  • Male or female, aged ≥18 years at the time the informed consent form (ICF) is signed. Exceptions are made for The Republic of South Korea and Taiwan where, according to local regulatory requirements, legal age is reached at 19 years and 20 years, respectively.
  • Confirmed diagnosis of primary ITP made at least 3 months before randomization and based on the American Society of Hematology Criteria, and no known etiology for thrombocytopenia
  • Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in the opinion of the investigator
  • Mean platelet count of <30×10E9/L from at least 3 documented, qualifying counts within the 3 preceding months where at least 2 of the qualifying counts must be taken during the screening period: 1 platelet count collected during the screening period and the predose platelet count on the day of randomization (visit 1). If the third count is not available from the 3 preceding months, this third platelet count can be obtained during the screening period.
  • A documented history of a platelet count of <30×10E9/L before screening
  • At the start of the trial, the participant either takes concurrent ITP treatment(s) and has received at least 1 prior therapy for ITP in the past, or the participant does not take treatment for ITP (see note) but has received at least 2 prior treatments for ITP. Participants receiving permitted concurrent ITP treatment(s) at baseline must have been stable in dose and frequency for at least 4 weeks before randomization.

Permitted concurrent ITP medications include corticosteroids, danazol, vinca alkaloids, oral immunosuppressants, dapsone, fostamatinib, and/or oral TPO-RAs.

Note: Participants not receiving concurrent ITP therapy are also eligible for the trial if they have not received prior ITP therapy for at least 4 weeks before baseline, and 6 months in case of prior ITP therapy with an anti-CD20 therapy (eg, rituximab).

  • Women of childbearing potential:

    • As defined in Woman of Childbearing Potential in the protocol, women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before trial medication can be administered
    • Must be on a stable regimen for at least 1 month of a highly effective or acceptable method of contraception during the trial and for 90 days after the last administration of IMP
  • Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use an acceptable method of contraception, ie, a condom from signing the ICF through the last administration of the IMP. Male participants are also not allowed to donate sperm during this time.

Exclusion criteria:

  • Secondary ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, thrombocytopenia associated with myeloid dysplasia, or hematopoietic stem cell transplant
  • Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 4 weeks prior to randomization
  • Use of any transfusions within 4 weeks prior to randomization
  • Use of Ig (IV, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks prior to randomization
  • Use of romiplostim within 4 weeks prior to randomization
  • Undergone splenectomy less than 4 weeks prior to randomization
  • Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP
  • Use of any monoclonal antibody or Fc fusion proteins, other than those previously indicated, within 6 months before the first dose of the IMP (eg, anti-CD20)
  • At the screening visit, clinically significant laboratory abnormalities as follows:

    o Hemoglobin ≤9 g/dL

  • OR -

    o International normalized ratio >1.5 or activated partial thromboplastin time >1.5×upper limit of normal

  • OR -

    o total IgG level <6 g/L

  • History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of IMP. Participants with the following cancer can be included at any time:

    1. Adequately treated basal cell or squamous cell skin cancer
    2. Carcinoma in situ of the cervix
    3. Carcinoma in situ of the breast or
    4. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
  • Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments
  • History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) within 12 months prior to randomization
  • History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia
  • Evidence of an active clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure based on the investigator's judgment (eg, intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for packed red blood cell transfusion)
  • Estimated high risk of a clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure according to the investigator's judgment
  • Clinical evidence of other significant serious diseases, have had a recent major surgery, or who have any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk
  • Positive serum test at screening for an active viral infection with any of the following conditions:

    1. Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HBV DNA test (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf)
    2. Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a negative HCV RNA test)
    3. Human immunodeficiency virus (HIV) based on test results that are associated with an acquired immunodeficiency syndrome (AIDS)-defining condition or a CD4 count ≤200 cells/mm3
  • Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients
  • Previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP
  • Pregnant or lactating females and those who intend to become pregnant during the trial or within 90 days after last dose of the IMP
  • Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
  • Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of ITP or put the participant at undue risk
  • Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITP (eg, cardiovascular, pulmonary, hematologic, gastrointestinal, endocrine, hepatic, renal, neurological, malignancy, infectious diseases, uncontrolled diabetes) despite appropriate treatments which could put the participant at undue risk
  • Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse
  • Received a live/live-attenuated vaccine less than 4 weeks before screening. The receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time before screening is not considered an exclusion criterion

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): NCT04687072


Contacts
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Contact: Antonio Guglietta, MD 857-350-4834 ext +1 clinicaltrials@argenx.com

Locations
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Sponsors and Collaborators
argenx
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Responsible Party: argenx
ClinicalTrials.gov Identifier: NCT04687072    
Other Study ID Numbers: ARGX-113-2004
First Posted: December 29, 2020    Key Record Dates
Last Update Posted: October 14, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations