Overview

This trial is active, not recruiting.

Condition relapsing-remitting multiple sclerosis
Treatments biib019 (daclizumab high yield process prefilled syringe), probe drug cocktail
Phase phase 3
Sponsor Biogen Idec
Start date November 2011
End date April 2013
Trial size 133 participants
Trial identifier NCT01462318, 205MS302

Summary

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Arm
(Experimental)
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.
biib019 (daclizumab high yield process prefilled syringe) DAC HYP
150 mg DAC HYP in 1 ml pre-filled syringe (PFS)
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

Primary Outcomes

Measure
Number of participants with anti-DAC HYP binding antibodies (ADAbs)
time frame: Up to 44 weeks
Number of participants with anti-DAC HYP neutralizing antibodies (NAbs)
time frame: Up to 44 weeks
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
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

Secondary Outcomes

Measure
Apparent clearance (CL/F) of daclizumab
time frame: Day 1 and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 44
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
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
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
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
Intensive PK sub-study: Trough concentrations (Ctrough) of daclizumab
time frame: Day 1 and Day 141 (Week 20) pre-dose
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
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
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
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
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
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

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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.

Additional Information

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)
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2014.
Information provided to ClinicalTrials.gov by Biogen Idec.