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

Primary Purpose

Relapsing-Remitting Multiple Sclerosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Midazolam
Caffeine
S-warfarin
Vitamin K
Omeprazole
Dextromethorphan
BIIB019 (Daclizumab)
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Relapsing-Remitting Multiple Sclerosis focused on measuring Pre-filled syringe, Pharmacokinetic, Daclizumab High Yield Process, immunogenicity

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site
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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DAC HYP

Arm 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.

Outcomes

Primary Outcome Measures

Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay
Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay
Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug
AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2).
TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio

Secondary Outcome Measures

Intensive PK Sub-study: Cmax of DAC HYP
Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP
Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP
Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP
Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP
Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP
Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP
TP-DI Sub-study: Cmax of Each Probe Drug
Cmax of each of the following CYP isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).
TP-DI Sub-study: CL/F of Each Probe Drug
CL/F of each of the following CYP isoenzyme substrates: midazolam (CYP3A), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).
TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing

Full Information

First Posted
July 14, 2011
Last Updated
January 23, 2017
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01462318
Brief Title
An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis
Acronym
OBSERVE
Official Title
A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics of BIIB019, Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis
Keywords
Pre-filled syringe, Pharmacokinetic, Daclizumab High Yield Process, immunogenicity

7. Study Design

Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
133 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DAC HYP
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
5 mg
Intervention Type
Other
Intervention Name(s)
Caffeine
Intervention Description
200 mg
Intervention Type
Drug
Intervention Name(s)
S-warfarin
Intervention Description
10 mg
Intervention Type
Other
Intervention Name(s)
Vitamin K
Intervention Description
10 mg
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Intervention Description
40 mg
Intervention Type
Drug
Intervention Name(s)
Dextromethorphan
Intervention Description
30 mg
Intervention Type
Biological
Intervention Name(s)
BIIB019 (Daclizumab)
Other Intervention Name(s)
Daclizumab High Yield Process; DAC HYP
Intervention Description
150 mg in 1 ml PFS
Primary Outcome Measure Information:
Title
Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay
Description
Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
Time Frame
Up to 44 weeks
Title
Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay
Description
Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).
Time Frame
Up to 44 weeks
Title
TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug
Description
AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2).
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
Title
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 Outcome Measure Information:
Title
Intensive PK Sub-study: Cmax of DAC HYP
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
Title
Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP
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
Title
Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP
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
Title
Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP
Time Frame
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
Title
Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP
Time Frame
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
Title
Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP
Time Frame
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
Title
Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP
Time Frame
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
Title
TP-DI Sub-study: Cmax of Each Probe Drug
Description
Cmax of each of the following CYP isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).
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
Title
TP-DI Sub-study: CL/F of Each Probe Drug
Description
CL/F of each of the following CYP isoenzyme substrates: midazolam (CYP3A), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).
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
Title
TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing
Time Frame
Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration) at 2 hours after probe drug cocktail administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
Research Site
City
Lake Barrington
State/Province
Illinois
ZIP/Postal Code
60010
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40513
Country
United States
Facility Name
Research Site
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Research Site
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37064
Country
United States
Facility Name
Research Site
City
Brno
ZIP/Postal Code
65691
Country
Czech Republic
Facility Name
Research Site
City
Jihlava
ZIP/Postal Code
58633
Country
Czech Republic
Facility Name
Research Site
City
Ostrava
ZIP/Postal Code
70852
Country
Czech Republic
Facility Name
Research Site
City
Pardubice
ZIP/Postal Code
53203
Country
Czech Republic
Facility Name
Research Site
City
Teplice
ZIP/Postal Code
41501
Country
Czech Republic
Facility Name
Research Site
City
Veszprem
State/Province
Korhazu 1
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
Research Site
City
Debrecen
ZIP/Postal Code
4031
Country
Hungary
Facility Name
Research Site
City
Esztergom
ZIP/Postal Code
2500
Country
Hungary
Facility Name
Research Site
City
Szekesfehervar
Country
Hungary
Facility Name
Research Site
City
Katowice
Country
Poland
Facility Name
Research Site
City
Krakow
ZIP/Postal Code
31-501
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
27411694
Citation
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.
Results Reference
derived

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

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