An Immunogenicity and Pharmacokinetics (PK) Study of BIIB019 (Daclizumab High Yield Process (DAC HYP)) Prefilled Syringe in Relapsing Remitting Multiple Sclerosis (RRMS)

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— OBSERVE  

Official title:

A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics (PK) of (BIIB019) Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01462318
• Other study ID #: 205MS302
• Secondary ID: 2010-023856-97
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 14, 2011
• Last updated: December 23, 2015
• Start date: November 2011
• Est. completion date: February 2016

Study information

• Verified date: December 2015
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: National Medicines InstituteCzech Republic: State Institute for Drug ControlRussia: Pharmacological Committee, Ministry of HealthHungary: National Institute of PharmacyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 pharmacokinetic (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).

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 monthly assessment of immunogenicity, pharmacokinetic (PK), pharmacodynamics (PD), 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 133
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• Must have a confirmed diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS) according to McDonald criteria and previous magnetic resonance imaging (MRI) 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 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 (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).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Probe drug cocktail
The probe drug cocktail consists of 5 mg oral midazolam, 200 mg caffeine,10 mg S-warfarin,10 mg vitamin K, 40 mg omeprazole, 30 mg dextromethorphan

Biological:
• BIIB019 (Daclizumab)
150 mg in 1 ml pre-filled syringe (PFS)

Locations

Country	Name	City	State
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Hradec Kralove
Czech Republic	Research Site	Ostrava
Czech Republic	Research Site	Pardubice
Czech Republic	Research Site	Prague
Czech Republic	Research Site	Teplice
Czech Republic	Research Site	Vysocina
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Esztergom
Hungary	Research Site	Szekesfehervar
Hungary	Research Site	Veszprem
Poland	Research Site	Katowice
Poland	Research Site	Krakow
United States	Research Site	Bradenton	Florida
United States	Research Site	Centennial	Colorado
United States	Research Site	Dayton	Ohio
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Franklin	Tennessee
United States	Research Site	Lake Barrington	Illinois
United States	Research Site	Lexington	Kentucky
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Czech Republic,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with anti-DAC HYP binding antibodies (ADAbs)		Up to 44 weeks	Yes
Primary	Number of participants with anti-DAC HYP neutralizing antibodies (NAbs)		Up to 44 weeks	Yes
Primary	Therapeutic protein-drug interactions (TP-DI) Sub-study: Area-under-the-curve from zero to infinity (AUC0-8) of each probe drug	AUC0-8 of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), omeprazole (CYP2C19), and dextromethorphan (CYP2D6)	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	No
Primary	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	No
Secondary	Apparent clearance (CL/F) of DAC HYP	A population PK approach will be utilized to characterize the PK of DAC HYP in the entire study population.	Up to Week 188	No
Secondary	Apparent volume of distribution (V/F) of DAC HYP	A population PK approach will be utilized to characterize the PK of daclizumab in the entire study population.	Up to Week 188	No
Secondary	Intensive PK sub-study: Maximum observed concentration (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	No
Secondary	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	No
Secondary	Intensive PK sub-study: Area-under-the-curve from start to end of the dosing interval (AUC) 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	No
Secondary	Intensive PK sub-study: Trough concentrations (Ctrough) 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	No
Secondary	Intensive PK sub-study: Apparent volume of distribution (V/F) 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	No
Secondary	Intensive PK sub-study: Elimination half-life (t½) 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	No
Secondary	Intensive PK sub-study: Apparent clearance (CL/F) 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	No
Secondary	TP-DI sub-study: Maximum observed concentration (Cmax) of each probe drug	Cmax of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), omeprazole (CYP2C19), and dextromethorphan (CYP2D6)	Weeks 43 and 53 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	No
Secondary	TP-DI Sub-study: Apparent Clearance (CL/F) of each probe drug	CL/F of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), omeprazole (CYP2C19), and dextromethorphan (CYP2D6)	Weeks 43 and 53 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	No
Secondary	TP-DI Sub-study: Omeprazole/hydroxyomeprazole concentration ratio at 2 hours post-omeprazole dosing		Week 43 and Week 52 at 2 hours after probe drug cocktail administration	No