Phase II Study of Teriflunomide as Adjunctive Therapy to Interferon-beta in Subjects With Multiple Sclerosis

NCT00489489 | Completed Phase 2 Results DMC

• 3 other identifiers: PDY60452006-003134-14HMR1726D-2003
• Study Type: interventional
• Target: 118
• Locations: 5 countries
• Sites: 5

Brief Summary

The primary objective was to estimate the tolerability and safety of 2 doses of teriflunomide administered once daily for 24 weeks, compared with placebo, in patients with multiple sclerosis \[MS\] with relapses who were on a stable dose of interferon-β \[IFN-β\]. Secondary objectives were:

• to estimate the effects of the 2 doses of teriflunomide, compared to placebo, in combination with a stable dose of IFN-β on Magnetic Resonance Imaging \[MRI\] parameters, relapse rate and patient-reported fatigue;
• to perform pharmacokinetic analyses of the 2 doses of teriflunomide in combination with a stable dose of IFN-β.

Conditions

Multiple Sclerosis

Keywords

MS; interferon-beta; adjunctive therapy; relapses

Outcome Measures

Primary Outcomes (3)

• Overview of Adverse Events [AE]

  AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

  from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)

• Overview of AE With Potential Risk of Occurrence

  AE with potential risk of occurrence were defined as follows: * Hepatic disorders; * Immune effects, mainly effects on bone marrow and infection; * Pancreatic disorders; * Malignancy; * Skin disorders, mainly Hair loss and Hair thinning; * Pulmonary disorders; * Hypertension; * Peripheral neuropathy; * Psychiatric disorders; * Hypersensitivity.

  from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)

• Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)

  PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Hepatic parameters thresholds were defined as follows: * Alanine Aminotransferase \[ALT\] \>3, 5, 10 or 20 Upper Normal Limit \[ULN\]; * Aspartate aminotransferase \[AST\] \>3, 5, 10 or 20 ULN; * Alkaline Phosphatase \>1.5 ULN; * Total Bilirubin \[TB\] \>1.5 or 2 ULN; * ALT \>3 ULN and TB \>2 ULN;

  from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)

Secondary Outcomes (5)

• Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)

  baseline (before randomization) and 24 weeks

• Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)

  24 weeks

• Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan

  24 weeks

• Annualized Relapse Rate [ARR]: Poisson Regression Estimates

  24 weeks

• Pharmacokinetic [PK]: Teriflunomide Plasma Concentration

  24 weeks

Study Arms (3)

Teriflunomide 7 mg + IFN-β

EXPERIMENTAL

Teriflunomide 7 mg once daily concomitantly with Interferon-β (IFN-β) for 24 weeks

Drug: Teriflunomide; Drug: Interferon-β

Teriflunomide 14 mg + IFN-β

EXPERIMENTAL

Teriflunomide 14 mg once daily concomitantly with Interferon-β (IFN-β) for 24 weeks

Drug: Teriflunomide; Drug: Interferon-β

Placebo + IFN-β

PLACEBO COMPARATOR

Placebo (for Teriflunomide) once daily concomitantly with Interferon-β (IFN-β) for 24 weeks

Drug: Placebo (for Teriflunomide); Drug: Interferon-β

Interventions

Teriflunomide DRUG

Film-coated tablet Oral administration

Also known as: HMR1726

Teriflunomide 14 mg + IFN-β; Teriflunomide 7 mg + IFN-β

Placebo (for Teriflunomide) DRUG

Film-coated tablet Oral administration

Placebo + IFN-β

Interferon-β DRUG

Powder for reconstitution, of any licensed strength for either intramuscular or subcutaneous injection

Also known as: Avonex®, Rebif®, Betaseron®

Placebo + IFN-β; Teriflunomide 14 mg + IFN-β; Teriflunomide 7 mg + IFN-β

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Definite MS diagnosis according to McDonald's criteria;
• Relapsing clinical course, with or without progression;
• Expanded Disability Status Scale \[EDSS\] less or equal to 5.5 (ambulatory);
• Stable dose of IFN-β for at least 26 weeks prior to the screening visit;
• No onset of MS relapse in the preceding 60 days prior to randomization;
• Clinically stable for 4 weeks prior to randomization.

You may not qualify if:

• Other chronic disease of the immune system, liver function impairment or chronic pancreatic disease;
• Pregnant or nursing woman;
• Alcohol or drug abuse;
• Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
• Human immunodeficiency virus \[HIV\] positive status;
• Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (5)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

Laval, Canada

Location

Sanofi-Aventis Administrative Office

Berlin, Germany

Location

Sanofi-Aventis Administrative Office

Milan, Italy

Location

Sanofi-Aventis Administrative Office

Barcelona, Spain

Location

Related Publications (1)

• Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012 Jun 5;78(23):1877-85. doi: 10.1212/WNL.0b013e318258f7d4. Epub 2012 May 23.

  PMID: 22622860 RESULT

MeSH Terms

Conditions

Multiple Sclerosis; Recurrence

Interventions

teriflunomide; Interferon beta-1a; Interferon beta-1b

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi-aventis

Contact_US@sanofi-aventis.com

Study Officials

• ICD

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 21, 2007
• Study Start: May 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: November 6, 2012
• Results First Posted: November 2, 2012

Record last verified: 2012-11

Locations

IT (1); US (1); CA (1); DE (1); ES (1)