Phase 3
N=133
An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT01462318 ↗Enrolled (actual)
133
Serious AEs
24.8%
Results posted
Mar 2017
Primary outcome: Primary: Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay — 78; 35; 92; 21 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Midazolam (Drug); Caffeine (Other); S-warfarin (Drug); Vitamin K (Other); Omeprazole (Drug); Dextromethorphan (Drug); BIIB019 (Daclizumab) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Biogen
- Primary completion
- Jan 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay |
78; 35; 92; 21; 89; 21 | — |
| PRIMARY Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay |
105; 8; 109; 4; 104; 6 | — |
| PRIMARY TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug |
786.75; 816.87; 19292.9; 19609.3; 2214.5; 1770.0 | — |
| PRIMARY TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio |
0.42468; 0.48939 | — |
| SECONDARY Intensive PK Sub-study: Cmax of DAC HYP |
12.63; 29.07 | — |
| SECONDARY Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP |
9.31; 6.41 | — |
| SECONDARY Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP |
255.25; 638.10 | — |
| SECONDARY Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP |
14.93 | — |
| SECONDARY Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP |
8.21 | — |
| SECONDARY Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP |
21.92 | — |
| SECONDARY Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP |
0.27 | — |
| SECONDARY TP-DI Sub-study: Cmax of Each Probe Drug |
271.05; 311.21; 4965.0; 5399.5; 635.65; 649.74 | — |
| SECONDARY TP-DI Sub-study: CL/F of Each Probe Drug |
7625.7; 7298.6; 565.86; 541.46; 41612.4; 41772.4 | — |
| SECONDARY TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing |
2.673; 1.028 | — |
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 pharmacokinetics (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).
Eligibility Criteria
Key Inclusion Criteria
- Must have a confirmed diagnosis of RRMS according to McDonald criteria and previous cranial magnetic resonance imaging demonstrating lesion(s) consistent with MS
- 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 (NCT01462318) 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 interferon (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 (NCT01462318) 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 ≤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.
Data sourced from ClinicalTrials.gov (NCT01462318). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.