An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis (OBSERVE)

Biogen

Status and phase: Completed; Phase 3

Conditions: Relapsing-Remitting Multiple Sclerosis

Treatments: Drug: S-warfarin; Drug: Omeprazole; Biological: BIIB019 (Daclizumab); Drug: Midazolam; Other: Caffeine; Other: Vitamin K; Drug: Dextromethorphan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01462318

205MS302

2010-023856-97 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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 assessment of immunogenicity, PK, pharmacodynamics, 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: (1) 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 (2) 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.

Enrollment: 133 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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133 participants in 1 patient group

DAC HYP

Experimental group

Description:

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. The probe-drug cocktail consists of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg. The oral vitamin K is used to counteract warfarin's anticoagula nt effect prophylactically.

Treatment:

Drug: S-warfarin

Other: Caffeine

Drug: Dextromethorphan

Drug: Omeprazole

Biological: BIIB019 (Daclizumab)

Other: Vitamin K

Drug: Midazolam