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

NCT ID: NCT01462318

Last Updated: 2017-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2016-01-31

Brief 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).

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 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.

Conditions

Relapsing-Remitting Multiple Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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. 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.

Group Type: EXPERIMENTAL

Midazolam

Intervention Type: DRUG

5 mg

Caffeine

Intervention Type: OTHER

200 mg

S-warfarin

Intervention Type: DRUG

10 mg

Vitamin K

Intervention Type: OTHER

10 mg

Omeprazole

Intervention Type: DRUG

40 mg

Dextromethorphan

Intervention Type: DRUG

30 mg

BIIB019 (Daclizumab)

Intervention Type: BIOLOGICAL

150 mg in 1 ml PFS

Interventions

Midazolam

5 mg

Intervention Type: DRUG

Caffeine

200 mg

Intervention Type: OTHER

S-warfarin

10 mg

Intervention Type: DRUG

Vitamin K

10 mg

Intervention Type: OTHER

Omeprazole

40 mg

Intervention Type: DRUG

Dextromethorphan

30 mg

Intervention Type: DRUG

BIIB019 (Daclizumab)

150 mg in 1 ml PFS

Intervention Type: BIOLOGICAL

Other Intervention Names

Daclizumab High Yield Process; DAC HYP

Eligibility Criteria

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

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).

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).

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

Research Site

Centennial, Colorado, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Lake Barrington, Illinois, United States

Research Site

Lexington, Kentucky, United States

Research Site

Farmington Hills, Michigan, United States

Research Site

Dayton, Ohio, United States

Research Site

Franklin, Tennessee, United States

Research Site

Brno, , Czechia

Research Site

Jihlava, , Czechia

Research Site

Ostrava, , Czechia

Research Site

Pardubice, , Czechia

Research Site

Teplice, , Czechia

Research Site

Veszprém, Korhazu 1, Hungary

Research Site

Budapest, , Hungary

Research Site

Debrecen, , Hungary

Research Site

Esztergom, , Hungary

Research Site

Székesfehérvár, , Hungary

Research Site

Katowice, , Poland

Research Site

Krakow, , Poland

Countries

United States; Czechia; Hungary; Poland

References

Gold R, Stefoski D, Selmaj K, Havrdova E, Hurst C, Holman J, Tornesi B, Akella S, McCroskery P. Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. Neurol Ther. 2016 Dec;5(2):169-182. doi: 10.1007/s40120-016-0048-2. Epub 2016 Jul 13.

Reference Type: DERIVED

PMID: 27411694 (View on PubMed)

Other Identifiers

2010-023856-97

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205MS302

Identifier Type: -

Identifier Source: org_study_id