An Immunogenicity and Pharmacokinetics (PK) Study of DAC HYP Prefilled Syringe in Relapsing Remitting Multiple Sclerosis (RRMS) (OBSERVE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01462318
First received: July 14, 2011
Last updated: September 12, 2013
Last verified: February 2013
  Purpose

The primary purpose of this study is to characterize the immunogenicity and pharmacokinetics (PK) of DAC HYP when administered as an SC injection using the PFS. The DAC PFS injection will be administered every 4 weeks. Additionally, intensive PK data will be obtained in a subset of subjects.Also, a therapeutic protein - drug interaction (TP-DI) sub study will be done at selected sites.


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Biological: Daclizumab High Yield Process prefilled syringe
Drug: Probe drug cocktail
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics (PK) of Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS)

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Safety as a measure of the incidence of anti-DAC HYP binding antibodies (ADAbs) [ Time Frame: Patients will be followed for a maximum duration of 44 weeks ] [ Designated as safety issue: Yes ]
  • Safety as a measure of the incidence of anti-DAC HYP neutralizing antibodies (NAbs) [ Time Frame: Patients will be followed for a maximum duration of 44 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dac Population PK parameters including apparent clearance and volume of distribution [ Time Frame: week 44 ] [ Designated as safety issue: No ]
  • Dac PK parameters for subjects in intensive PK substudy [ Time Frame: Up to week 20 ] [ Designated as safety issue: No ]
  • PK parameters for individual probe drugs for subjects in the TP-DI substudy [ Time Frame: Week 43 to week 53 ] [ Designated as safety issue: No ]

Estimated Enrollment: 135
Study Start Date: October 2011
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DAC HYP Prefilled filled syringe Biological: Daclizumab High Yield Process prefilled syringe
150mg DAC HYP in 1ml pre-filled syringe
Drug: Probe drug cocktail
5 mg oral midazolam, 200mg caffeine, 10 mg S-warfarin,10 mg vit K, 40mg omeprazole, 30mg dextromethrorphan

Detailed Description:

Following a screening period, subjects will recieve DAC HYP over a 24 week treatment( 6 monthly injections) and than enter a 20 week washout period for monthly assessment of immunogenicity, PK,PD safety and tolerability. The 20 week washout is necessary to ensure measurement of ADAbs and NAbs in the absence of drug interference. After washout, the patients may resume monthly treatment with DAC HYP 150 Mg for an addittional 3 years. All subjects will be followed for 6 months after their last dose for safety monitoring.

Additionally, 2 sub studies will be performed; An intensive serial PK sampling performed over the first and last dosing interval folllowing DAC HYP doses administered at week 0 and at week 20.

For the TP-DI substudy, a probe drug cocktail will be administered and sampling carried out 96 hours after administration of a probe drug cocktail at week 43 and at week 53. A maximum of 20 patients will be enrolled in the TP-DI substudy.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of registration:

  • Aged 18 to 65 years old, inclusive, at the time of informed cosnent
  • Must have a confirmed diagnosis of RRMS according to McDonald criteria and previous MRI showing lesion
  • Must have a baseline 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 monthsh after the last dose

Exclusion Criteria:

Unless otherwise specified, candidates will be excluede from study entry if any of the following exclusion criteria exsist at the time of registration:

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

Inclusion criteria for the TP-DI Substudy:

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 LFT results (total bilirubin ≤1.5 × ULN, 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).

Other protocol-defined inclusion/exclusion criteria will apply for the 3 year extension study and the TP-DI substudy as per protocol version 4 dated 28 Sep 2012, section 8.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01462318

Locations
United States, Colorado
Research Site
Centennial, Colorado, United States
United States, District of Columbia
Research Site
Washington, District of Columbia, United States
United States, Florida
Research Site
Bradenton, Florida, United States
United States, Illinois
Research Site
Lake Barrington, Illinois, United States
United States, Michigan
Research Site
Farmington Hills, Michigan, United States
United States, Ohio
Research Site
Dayton, Ohio, United States
United States, Tennessee
Research Site
Franklin, Tennessee, United States
Czech Republic
Research Site
Brno, Czech Republic
Research Site
Hradec Kralove, Czech Republic
Research Site
Jihlava, Czech Republic
Research Site
Ostrava, Czech Republic
Research Site
Pardubice, Czech Republic
Research Site
Teplice, Czech Republic
Hungary
Research Site
Budapest, Hungary
Research Site
Debrecen, Hungary
Research Site
Eger, Hungary
Research Site
Esztergom, Hungary
Research Site
Nyiregyhaza, Hungary
Research Site
Veszprem, Hungary
Poland
Research Site
Katowice, Poland
Research Site
Krakow, Poland
Sponsors and Collaborators
Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT01462318     History of Changes
Other Study ID Numbers: 205MS302
Study First Received: July 14, 2011
Last Updated: September 12, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Russia: Pharmacological Committee, Ministry of Health
Poland: Office for Medicinal Products
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy

Keywords provided by Biogen Idec:
Pre-filled syringe
Pharmacokinetic
Daclizumab High Yield Process
immunogenicity

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Daclizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014