Clinical trial NCT01058005: Study Evaluating Rebif, Copaxone, and Tysabri for Active Multiple Sclerosis
Official title: A Multicenter, Randomized, Open-Label, Parallel-Group, Active-Controlled Study to Evaluate the Benefits of Switching Therapy (Glatiramer Acetate or Interferon Beta-1a) to Natalizumab in Subjects With Relapsing Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: MS
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Elan Pharmaceuticals
First posted: 2010-01-28
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: This was a multicenter, randomized, open-label, parallel-group, active-controlled study. Prior to randomization, participants were to have been treated with glatiramer acetate or interferon β-1a (44 μg). Participants were to be randomized to receive natalizumab, interferon β-1a 44 μg, or glatiramer acetate.

Detailed description: The protocol was amended in 15 March 2011 to discontinue participants' enrollment and efficacy assessments, and to offer the opportunity for participants already enrolled to continue receiving study treatment for their planned participation in the study. The study had been active in several countries for approximately 1 year, and enrollment had been significantly slower than expected. Thus, the decision was made by the Sponsor to terminate the study since current and projected future enrollment rates would not have provided valuable information in a reasonable timeframe. All clinical efficacy and magnetic resonance imaging (MRI) procedures were removed from the protocol, and safety assessments were to be managed through standard of care activities.

Eligibility criteria: Key Inclusion Criteria:

1. Have a diagnosis of relapsing remitting multiple sclerosis (MS) as defined by the revised McDonald Committee criteria (Polman 2005).
2. Must have been treated with a stable regimen of either glatiramer acetate (20 mg per day subcutaneous) or interferon beta-1a (44 mcg 3 times per week subcutaneous) as their principal first therapy for MS for 6 to 18 months prior to randomization. (Note: prior treatment with another MS therapy of ≤ 30 days total duration is not exclusionary \[e.g. titration to 44 mcg is allowed\]).
3. Have had disease activity within 12 months prior to screening while on therapy; disease activity must be observed after a minimum of 6 months on therapy. Qualifying disease activity is defined as:

   * One or more clinical relapses OR
   * Two or more new MRI lesions (gadolinium \[Gd+\] and/or T2 hyperintense) For inclusion purposes: (a) a relapse is defined as neurologic signs and/or symptoms documented in the medical record by a neurologist and of sufficient duration to be determined by the Investigator or the Treating Physician as consistent with an MS relapse or (b) MRI activity must be verified by the central reader center.
4. Be naïve to natalizumab.
5. Have a documented Expanded Disability Status Scale (EDSS) score between 0.0 and 5.5, inclusive.

Key Exclusion Criteria:

1. Have a diagnosis of primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Patients with these conditions may also have superimposed relapses, but are distinguished from relapsing-remitting patients by the lack of clinically stable periods or clinical improvement.
2. Have known intolerance, contraindication to, or history of non-compliance with, the use of glatiramer acetate or interferon beta-1a.
3. Have had an MS exacerbation (relapse) within 30 days prior to randomization AND/OR the patient has not stabilized from a previous relapse, in the opinion of the Investigator, prior to randomization.
4. The patient is considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or due to prior immunosuppressive or immunomodulating treatment.
5. Subjects for whom MRI is contraindicated, i.e., have pacemakers or other contraindicated implanted metal devices, have suffered or are at risk for side effects from gadolinium (Gd), or have claustrophobia that cannot be medically managed.
6. History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical trial.
7. History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
8. Known history of human immunodeficiency virus (HIV).
9. Positive test result for hepatitis C virus (test for hepatitis C virus antibody \[HCVAb\]) or hepatitis B virus (test for hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\]).
10. History of transplantation or any anti-rejection therapy.
11. History of progressive multifocal leukoencephalopathy (PML).

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Incidence of Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: up to 108 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Fort Collins
country: United States
facility: Research Site
state: Colorado
city: Maitland
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Patchogue
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Franklin
country: United States
facility: Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Kirkland
country: United States
facility: Research Site
state: Washington
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
city: Fitzroy
country: Australia
facility: Research Site
state: Victoria
city: Gatineau
country: Canada
facility: Research Site
state: Quebec
city: Pardubice
country: Czech Republic
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
state: Bas-Rhin
city: Esztergom
country: Hungary
facility: Research Site
state: Komárom-Esztergom
city: Budapest
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Lódz
country: Poland
facility: Research Site
state: Lodzkie
city: Bialystok
country: Poland
facility: Research Site
state: Podlaskie
city: Gdansk
country: Poland
facility: Research Site
state: Pomorskie
city: Ljubljana
country: Slovenia
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santa Cruz de Tenerife
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Molndal
country: Sweden
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: