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An Immunogenicity and Pharmacokinetics (PK) Study of BIIB019 (Daclizumab High Yield Process (DAC HYP)) Prefilled Syringe in Relapsing Remitting Multiple Sclerosis (RRMS) (OBSERVE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01462318
First received: July 14, 2011
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

The primary objective of the study is to assess the immunogenicity of Daclizumab High Yield Process (DAC HYP) 150 mg administered every 4 weeks by subcutaneous (SC) injection using the pre-filled syringe (PFS) in participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives of this study are to characterize the pharmacokinetic (PK) of DAC HYP following single and multiple doses of DAC HYP administered by the PFS in a subset of participants with RRMS and to evaluate the effect of DAC HYP on the PK of probe drugs for cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A).


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Biological: BIIB019 (Daclizumab High Yield Process prefilled syringe)
Drug: Probe drug cocktail
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics (PK) of (BIIB019) Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS)

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Number of participants with anti-DAC HYP binding antibodies (ADAbs) [ Time Frame: Up to 44 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants with anti-DAC HYP neutralizing antibodies (NAbs) [ Time Frame: Up to 44 weeks ] [ Designated as safety issue: Yes ]
  • Therapeutic protein-drug interactions (TP-DI) Sub-study: Area-under-the-curve from zero to infinity (AUC0-∞) of each probe drug [ Time Frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration ] [ Designated as safety issue: No ]
    AUC0-∞ of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), omeprazole (CYP2C19), and dextromethorphan (CYP2D6)

  • TP-DI sub-study: Dextromethorphan to dextrorphan urine concentration ratio [ Time Frame: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Apparent clearance (CL/F) of daclizumab [ Time Frame: Day 1 and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 44 ] [ Designated as safety issue: No ]
    A population PK approach will be utilized to characterize the PK of daclizumab in the entire study population.

  • Apparent volume of distribution (V/F) of daclizumab [ Time Frame: Day 1 and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 44 ] [ Designated as safety issue: No ]
    A population PK approach will be utilized to characterize the PK of daclizumab in the entire study population.

  • Intensive PK sub-study: Maximum observed concentration (Cmax) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose ] [ Designated as safety issue: No ]
  • Intensive PK sub-study: time to reach maximum concentration (Tmax) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose ] [ Designated as safety issue: No ]
  • Intensive PK sub-study: Area-under-the-curve from start to end of the dosing interval (AUCtau) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose ] [ Designated as safety issue: No ]
  • Intensive PK sub-study: Trough concentrations (Ctrough) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) pre-dose ] [ Designated as safety issue: No ]
  • Intensive PK sub-study: Apparent volume of distribution (V/F) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose ] [ Designated as safety issue: No ]
  • Intensive PK sub-study: Elimination half-life (t½) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose ] [ Designated as safety issue: No ]
  • Intensive PK sub-study: Apparent clearance (CL/F) of daclizumab [ Time Frame: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose ] [ Designated as safety issue: No ]
  • TP-DI sub-study: Maximum observed concentration (Cmax) of each probe drug [ Time Frame: Weeks 43 and 53 pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration ] [ Designated as safety issue: No ]
    Cmax of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), omeprazole (CYP2C19), and dextromethorphan (CYP2D6)

  • TP-DI Sub-study: Apparent Clearance (CL/F) of each probe drug [ Time Frame: Weeks 43 and 53 pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration ] [ Designated as safety issue: No ]
    CL/F of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), omeprazole (CYP2C19), and dextromethorphan (CYP2D6)

  • TP-DI Sub-study: Omeprazole/hydroxyomeprazole concentration ratio at 2 hours post-omeprazole dosing [ Time Frame: Week 43 and Week 52 at 2 hours after probe drug cocktail administration ] [ Designated as safety issue: No ]

Enrollment: 133
Study Start Date: November 2011
Estimated Study Completion Date: January 2017
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DAC HYP

DAC HYP 150 mg by a subcutaneous (SC) injection using the pre-filled syringe (PFS) every 4 weeks for 24 weeks followed by a 20-week washout period. After completion of the washout period, participants may resume monthly DAC HYP 150 mg using the PFS for up to 3 additional years.

Participants in the TP-DI sub-study will receive probe-drug cocktail administration at Weeks 43 and 53.

Biological: BIIB019 (Daclizumab High Yield Process prefilled syringe)
150 mg DAC HYP in 1 ml pre-filled syringe (PFS)
Other Name: DAC HYP
Drug: Probe drug cocktail
The probe drug cocktail consists of 5 mg oral midazolam, 200 mg caffeine,10 mg S-warfarin,10 mg vitamin K, 40 mg omeprazole, 30 mg dextromethorphan

Detailed Description:

Following a screening period, participants will receive DAC HYP over a 24-week treatment period (6 monthly injections) and then enter a 20-week washout period for monthly assessment of immunogenicity, pharmacokinetic (PK), pharmacodynamics (PD), safety and tolerability. The 20-week washout is necessary to ensure measurement of anti-DAC HYP binding antibodies (ADAbs) and neutralizing antibodies (NAbs) in the absence of drug interference. After washout, the participants may resume monthly treatment with DAC HYP 150 mg for an additional 3 years. All participants will be followed for 6 months after their last dose for safety monitoring. Additionally, two sub-studies will be performed; an intensive serial PK sampling performed over the first and last dosing interval following DAC HYP doses administered at week 0 and at week 20, and a therapeutic protein-drug interaction (TP-DI) sub-study, during which a probe drug cocktail will be administered at weeks 43 and 53 followed by serial probe-drug PK sampling up to 96 hours after probe-drug administration. A maximum of 20 participants will be enrolled in the TP-DI sub-study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have a confirmed diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS) according to McDonald criteria and previous magnetic resonance imaging (MRI) showing lesion
  • Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive
  • Must have had 1 or more clinical relapses within the previous 2 years
  • Women of child bearing potential must be willing to practice effective contraception during the study and 4 months after the last dose

Key Exclusion Criteria:

  • Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease
  • Female subjects who are currently pregnant or breastfeeding

Key Inclusion criteria for 3-Year Treatment Extension:

To be eligible for participation in the 3-year treatment extension, participants must meet the following eligibility criteria at the time of reinitiation of DAC HYP:

  • Must have been compliant with the 205MS302 protocol during the initial 24-week treatment period and the 20-week washout period in the opinion of the Investigator.
  • Must resume DAC HYP treatment 12 weeks after completion of the washout period (i.e., 12 weeks after their Week 44 visit).
  • Participants who are currently receiving an approved IFN ß preparation must discontinue IFN ß treatment at the time of reinitiation of DAC HYP dosing (no washout is required).

Key Inclusion criteria for the TP-DI Sub-study:

To be eligible for participation in the TP-DI Sub-Study, subjects must meet the following eligibility criteria at the Screening Visit at Week 40:

  • Must have been compliant with the 205MS302 protocol during the initial 24-week treatment period and through Week 40 of the 20-week washout period in the opinion of the Investigator.
  • Must agree to resume DAC HYP treatment 12 weeks after completion of the washout period (i.e., 12 weeks after their Week 44 visit).
  • Must have normal liver function test results (total bilirubin ≤1.5 × upper limit of normal (ULN), alanine aminotransferase/ aspartate aminotransferase (ALT/AST) ≤2 × ULN, and prothrombin time/partial thromboplastin time ≤1.2 × ULN).
  • Must have normal renal function as estimated creatinine clearance >60 mL/min (Cockcroft-Gault formula).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462318

Locations
United States, Colorado
Research Site
Centennial, Colorado, United States
United States, District of Columbia
Research Site
Washington, District of Columbia, United States
United States, Florida
Research Site
Bradenton, Florida, United States
United States, Illinois
Research Site
Lake Barrington, Illinois, United States
United States, Michigan
Research Site
Farmington Hills, Michigan, United States
United States, Ohio
Research Site
Dayton, Ohio, United States
United States, Tennessee
Research Site
Franklin, Tennessee, United States
Czech Republic
Research Site
Brno, Czech Republic
Research Site
Hradec Kralove, Czech Republic
Research Site
Jihlava, Czech Republic
Research Site
Ostrava, Czech Republic
Research Site
Pardubice, Czech Republic
Research Site
Teplice, Czech Republic
Hungary
Research Site
Budapest, Hungary
Research Site
Debrecen, Hungary
Research Site
Eger, Hungary
Research Site
Esztergom, Hungary
Research Site
Nyiregyhaza, Hungary
Research Site
Veszprem, Hungary
Poland
Research Site
Katowice, Poland
Research Site
Krakow, Poland
Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT01462318     History of Changes
Other Study ID Numbers: 205MS302
Study First Received: July 14, 2011
Last Updated: October 13, 2014
Health Authority: United States: Institutional Review Board
Poland: National Medicines Institute
Czech Republic: State Institute for Drug Control
Russia: Pharmacological Committee, Ministry of Health
Hungary: National Institute of Pharmacy
United States: Food and Drug Administration

Keywords provided by Biogen Idec:
Pre-filled syringe
Pharmacokinetic
Daclizumab High Yield Process
immunogenicity

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Daclizumab
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 19, 2014