NCT01462318

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
133

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Nov 2011

Typical duration for phase_3

Geographic Reach
4 countries

19 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 14, 2011

Completed
4 months until next milestone

First Posted

Study publicly available on registry

October 31, 2011

Completed
1 day until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

March 14, 2017

Completed
Last Updated

March 14, 2017

Status Verified

January 1, 2017

Enrollment Period

4.2 years

First QC Date

July 14, 2011

Results QC Date

January 23, 2017

Last Update Submit

January 23, 2017

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

Pre-filled syringePharmacokineticDaclizumab High Yield Processimmunogenicity

Outcome Measures

Primary Outcomes (4)

  • 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).

    Up to 44 weeks

  • 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).

    Up to 44 weeks

  • 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).

    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

  • TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio

    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 Outcomes (10)

  • Intensive PK Sub-study: Cmax of DAC HYP

    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

  • Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP

    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

  • Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP

    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

  • Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP

    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

  • Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP

    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

  • +5 more secondary outcomes

Study Arms (1)

DAC HYP

EXPERIMENTAL

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.

Drug: MidazolamOther: CaffeineDrug: S-warfarinOther: Vitamin KDrug: OmeprazoleDrug: DextromethorphanBiological: BIIB019 (Daclizumab)

Interventions

MidazolamDRUG

5 mg

DAC HYP
CaffeineOTHER

200 mg

DAC HYP
S-warfarinDRUG

10 mg

DAC HYP
Vitamin KOTHER

10 mg

DAC HYP
OmeprazoleDRUG

40 mg

DAC HYP
DextromethorphanDRUG

30 mg

DAC HYP
BIIB019 (Daclizumab)BIOLOGICAL

150 mg in 1 ml PFS

Also known as: Daclizumab High Yield Process; DAC HYP
DAC HYP

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Research Site

Centennial, Colorado, 80112, United States

Location

Research Site

Washington D.C., District of Columbia, 20057, United States

Location

Research Site

Lake Barrington, Illinois, 60010, United States

Location

Research Site

Lexington, Kentucky, 40513, United States

Location

Research Site

Farmington Hills, Michigan, 48334, United States

Location

Research Site

Dayton, Ohio, 45417, United States

Location

Research Site

Franklin, Tennessee, 37064, United States

Location

Research Site

Brno, 65691, Czechia

Location

Research Site

Jihlava, 58633, Czechia

Location

Research Site

Ostrava, 70852, Czechia

Location

Research Site

Pardubice, 53203, Czechia

Location

Research Site

Teplice, 41501, Czechia

Location

Research Site

Veszprém, Korhazu 1, 8200, Hungary

Location

Research Site

Budapest, 1134, Hungary

Location

Research Site

Debrecen, 4031, Hungary

Location

Research Site

Esztergom, 2500, Hungary

Location

Research Site

Székesfehérvár, Hungary

Location

Research Site

Katowice, Poland

Location

Research Site

Krakow, 31-501, Poland

Location

Related Publications (1)

  • 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.

    PMID: 27411694DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

MidazolamCaffeineWarfarinVitamin KOmeprazoleDextromethorphanDaclizumabdaclizumab HYP

Condition Hierarchy (Ancestors)

Multiple SclerosisDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsXanthinesAlkaloidsPurinonesPurines4-HydroxycoumarinsCoumarinsBenzopyransPyransHeterocyclic Compounds, 1-RingNaphthoquinonesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPhytolDiterpenesTerpenesPolycyclic Compounds2-PyridinylmethylsulfinylbenzimidazolesSulfoxidesSulfur CompoundsPyridinesBenzimidazolesMorphinansOpiate AlkaloidsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsPhenanthrenesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Biogen Study Medical Director
Organization
Biogen
clinicaltrials@biogen.com

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 14, 2011

First Posted

October 31, 2011

Study Start

November 1, 2011

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

March 14, 2017

Results First Posted

March 14, 2017

Record last verified: 2017-01

Locations

US(7)CZ(5)HU(5)PL(2)