Efficacy and Safety Study of Peginterferon Beta-1a in Participants With Relapsing Multiple Sclerosis

Relapsing Multiple Sclerosis Clinical Trial

— ADVANCE  

Official title:

A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of PEGylated Interferon Beta-1a (BIIB017) in Subjects With Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00906399
• Other study ID #: 105MS301
• Secondary ID: 2008-006333-27
• Status: Completed
• Phase: Phase 3
• First received: May 20, 2009
• Last updated: September 15, 2014
• Start date: June 2009
• Est. completion date: October 2013

Study information

• Verified date: September 2014
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Romania: Ministry of Public HealthSpain: Agencia Española de Medicamentos y Productos SanitariosSerbia: Ethics CommitteeMexico: Federal Commission for Protection Against Health RisksUkraine: State Expert Centre of the Ministry of Health of UkraineGreece: Ministry of Health and WelfareGreece: Ethics CommitteeColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosEstonia: The State Agency of MedicineNew Zealand: MedsafeCzech Republic: State Institute for Drug ControlPeru: Instituto Nacional de SaludPoland: Ministry of HealthRussia: Ethics CommitteeNetherlands: Independent Ethics CommitteeCzech Republic: Ethics CommitteePeru: Ethics CommitteeGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesSerbia and Montenegro: Agency for Drugs and Medicinal DevicesCroatia: Ministry of Health and Social CareGeorgia: Ministry of HealthCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyLatvia: State Agency of MedicinesUnited States: Food and Drug AdministrationChile: Instituto de Salud Pública de ChileIndia: Central Drugs Standard Control OrganizationRomania: Ethics CommitteeRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the efficacy of peginterferon beta-1a in reducing the annualized relapse rate (ARR) in participants with relapsing multiple sclerosis (RMS) at 1 year. The secondary objectives of this study are to determine whether peginterferon beta-1a, at 1 year when compared with placebo, is effective in reducing the total number of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans, reducing the proportion of participants who relapse, and slowing the progression of disability.

Description:

This is a global multicenter, randomized, double-blind, parallel-group, placebo-controlled study. The treatment period is 96 weeks (2 years) in duration. Treatment Year 1 (Week 0 to Week 48) is referred to as the placebo-controlled treatment period of the study. At the beginning of Treatment Year 1, participants were randomized to receive placebo, peginterferon beta-1a 125 μg every 2 weeks, or peginterferon beta-1a 125 μg every 4 weeks. At the end of Treatment Year 1, participants in the placebo group were re-randomized to receive peginterferon beta-1a treatment so that during treatment Year 2 (Weeks 48 to Week 96) all participants received peginterferon beta-1a 125 μg every 2 or every 4 weeks. Per protocol, all primary and secondary endpoints pertain to Year 1 data.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1516
• Est. completion date: October 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• Must have a confirmed diagnosis of relapsing multiple sclerosis (RMS), as defined by McDonald criteria 1 through 4 (Polman, 2005)

• Must have an EDSS score between 0.0 and 5.0.

• Must have experienced at least 2 relapses that have been medically documented within the last 3 years with at least one occurring in the last 12 months

Key Exclusion Criteria:

• Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease

• Pregnant or nursing women

• Prior treatment with interferon could not exceed 4 weeks and subjects must have discontinued interferon treatment 6 months prior to Baseline

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• BIIB017 (peginterferon beta-1a)
Supplied as a liquid in pre-filled syringes to deliver 0.5 mL of 0.25 mg/mL (125 µg dose), self-administered by subcutaneous injection.
• Placebo
Matched placebo provided in pre-filled syringes, to deliver 0.5 mL self-administered by subcutaneous injection.

Locations

Country	Name	City	State
Belgium	Research Site	'Sint-Truiden
Belgium	Research Site	Bruxelles
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Chile	Research Site	Santiago
Colombia	Research Site	Barranquilla	Atlantico
Colombia	Research Site	Bogota	Cundinamarca
Colombia	Research Site	Bogota
Croatia	Research Site	Osijek
Croatia	Research Site	Zagreb
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Ostrava
Czech Republic	Research Site	Ostrava - Vitkovice
Czech Republic	Research Site	Ostrava-Poruba
Czech Republic	Research Site	Praha 2
Czech Republic	Research Site	Praha 5
Czech Republic	Research Site	Teplice
Estonia	Research Site	Parnu
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
France	Research Site	Amiens
France	Research Site	Clermont-Ferrand
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Nice
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Georgia	Research Site	Tbilisi
Germany	Research Site	Bayreuth
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Erbach
Germany	Research Site	Erlangen
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Koln
Germany	Research Site	Leipzig
Germany	Research Site	Marburg
Germany	Research Site	Munchen
Germany	Research Site	Munster
Germany	Research Site	Prien
Germany	Research Site	Ulm
Germany	Research Site	Westerstede
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
India	Research Site	Ahmedabad	Gujarat
India	Research Site	Amritsar	Punjab
India	Research Site	Bangalore	Karnataka
India	Research Site	Bangalore
India	Research Site	Chennai	Tamil Nadu
India	Research Site	Coimbatore	Tamil Nadu
India	Research Site	Indore	Madhyr Pradesh
India	Research Site	Jaipur	Rajasthan
India	Research Site	Kolkata	West Bengal
India	Research Site	Mangalore
India	Research Site	Mumbai	Maharashtra
India	Research Site	Nagpur	Maharashtra
India	Research Site	Nasik	Maharashtra
India	Research Site	Navi Mumbai
India	Research Site	Nehru Nagar
India	Research Site	New Delhi	Delhi
India	Research Site	New Delhi	Delhi
India	Research Site	Pune	Maharashtra
India	Research Site	Pune	Maharashtra
India	Research Site	Rajkot	Gujarat
India	Research Site	Saket	Delhi
Latvia	Research Site	Riga
Mexico	Research Site	Aquas Calientes
Mexico	Research Site	Chihuahua
Mexico	Research Site	Mexico City
Mexico	Research Site	Mexico DF
Mexico	Research Site	Monterrey, Nuevo Leon
Mexico	Research Site	Tijuana, Baja California
Netherlands	Research Site	Breda
Netherlands	Research Site	Nieuwegein
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Dunedin
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	San Isidro
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Konskie
Poland	Research Site	Krakow
Poland	Research Site	Krakow
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Plewiska
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Szczecin
Poland	Research Site	Warsawa
Poland	Research Site	Warsawa
Poland	Research Site	Warsawa
Poland	Research Site	Warsawa
Poland	Research Site	Wroclaw
Poland	Research Site	Zabrze
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Campulung
Romania	Research Site	Iasi
Romania	Research Site	Sibiu
Romania	Research Site	Targu Mures
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Kaluga
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Kursk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Ufa
Serbia	Research Site	Belgrade
Serbia	Research Site	Kragujevac
Serbia	Research Site	Nis
Spain	Research Site	Cordoba
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Sevilla
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Poltava
Ukraine	Research Site	Simferopol
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Vinnytsya
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Salford
United Kingdom	Research Site	Sheffield
United States	Research Site	Akron	Ohio
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Cleveland	Ohio
United States	Research Site	Des Moines	Iowa
United States	Research Site	Franklin	Tennessee
United States	Research Site	Lexington	Kentucky
United States	Research Site	Phoenix	Arizona
United States	Research Site	Ponte Vedra Beach	Florida
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Round Rock	Texas
United States	Research Site	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Chile,  Colombia,  Croatia,  Czech Republic,  Estonia,  France,  Georgia,  Germany,  Greece,  India,  Latvia,  Mexico,  Netherlands,  New Zealand,  Peru,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Ukraine,  United Kingdom, 

References & Publications (1)

Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, Liu S, Zhu Y, Seddighzadeh A, Hung S, Deykin A; ADVANCE Study Investigators. Pegylated interferon ß-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, doub — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Relapse Rate (ARR) at 1 Year	A relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings. Only relapses confirmed by an independent neurology evaluation committee (INEC) are included in the analysis. Data after participants switched to alternative multiple sclerosis (MS) medications are excluded. Data were analyzed using negative binomial regression, adjusted for baseline Expanded Disability Status Scale (EDSS) score (< 4 versus = 4), baseline age (< 40 versus = 40 years), and baseline relapse rate (number of relapses in 3 years prior to study entry divided by 3).	1 Year	No
Secondary	Number of New Or Newly Enlarging T2 Hyperintense Lesions at 1 Year	Number of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans. Data observed after participants switched to alternative MS medications are excluded. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions.	1 Year	No
Secondary	Proportion of Participants Relapsed at 1 Year	A relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurologic findings. Only relapses confirmed by INEC were included in the analysis. Estimated proportion of participants relapsed is based on the Kaplan-Meier product limit method.	Year 1	No
Secondary	Estimated Proportion of Participants With Sustained Disability Progression at 1 Year	Sustained disability progression is defined as: at least a 1.0 point increase on the EDSS from baseline EDSS = 1.0 that is sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks. The EDSS measures the disability status of people with MS on a scale that ranges from 0 to 10. The range of main categories include 0 (normal neurologic examination), to 5 (ambulatory without aid or rest for 200 meters/disability severe enough to impair full daily activities), to 10 (death due to MS). Estimated proportion of participants with progression based on the Kaplan-Meier product limit method.	1 Year	No