Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis

NCT00811395 | Completed Phase 2 Results DMC

• 3 other identifiers: LTS6047HMR1726D/20052007-003997-24
• Study Type: interventional
• Target: 182
• Locations: 7 countries
• Sites: 7

Brief Summary

The primary objective was to evaluate the long-term safety and tolerability of teriflunomide when added to treatment with interferon-β \[IFN-β\] or glatiramer Acetate \[GA\] in patients with multiple sclerosis \[MS\] with relapses. Secondary objectives were to evaluate the long-term effect on relapse rate, disability progression and Magnetic Resonance Imaging \[MRI\] parameters. This study is the extension study of the PDY6045 (NCT00489489) and PDY6046 (NCT00475865) studies. Participants who successfully completed the initial study were offered to continue their treatment (same compound, same dose) for 24 additional weeks.

Conditions

Multiple Sclerosis

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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)

• Overview of AE With Potential Risk of Occurence

  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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 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 in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)

Secondary Outcomes (6)

• Annualized Relapse Rate [ARR]: Poisson Regression Estimates

  48 weeks

• Overview of 12-week Sustained Disability Progression

  48 weeks

• Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints

  48 weeks

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

  baseline (before randomization in PDY6045 or PDY6046) and 48 weeks

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

  48 weeks

Study Arms (6)

Placebo + IFN-β

PLACEBO COMPARATOR

Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\] for 24 additional weeks

Drug: Placebo (for teriflunomide); Drug: Interferon-β [IFN-β]

Teriflunomide 7 mg + IFN-β

EXPERIMENTAL

Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\] for 24 additional weeks

Drug: Teriflunomide; Drug: Interferon-β [IFN-β]

Teriflunomide 14 mg + IFN-β

EXPERIMENTAL

Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\] for 24 additional weeks

Drug: Teriflunomide; Drug: Interferon-β [IFN-β]

Placebo + GA

PLACEBO COMPARATOR

Placebo (for teriflunomide) once daily concomitantly with glatiramer acetate \[GA\] for 24 additional weeks

Drug: Placebo (for teriflunomide); Drug: Glatiramer Acetate [GA]

Teriflunomide 7 mg + GA

EXPERIMENTAL

Teriflunomide 7 mg once daily concomitantly with glatiramer acetate \[GA\] for 24 additional weeks

Drug: Teriflunomide; Drug: Glatiramer Acetate [GA]

Teriflunomide 14 mg + GA

EXPERIMENTAL

Teriflunomide 14 mg once daily concomitantly with glatiramer acetate \[GA\] for 24 additional weeks

Drug: Teriflunomide; Drug: Glatiramer Acetate [GA]

Interventions

Teriflunomide DRUG

Film-coated tablet Oral administration

Also known as: HMR1726

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

Placebo (for teriflunomide) DRUG

Film-coated tablet Oral administration

Placebo + GA; Placebo + IFN-β

Interferon-β [IFN-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

Glatiramer Acetate [GA] DRUG

Solution in prefilled syringe for subcutaneous injection

Also known as: Copaxone®

Placebo + GA; Teriflunomide 14 mg + GA; Teriflunomide 7 mg + GA

Eligibility Criteria

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

You may qualify if:

• PDY6045 or PDY6046 participant who:
• completed the week 24 visit of either study PDY6045 or PDY6046,
• was still meeting eligibility criteria for receiving treatment,
• had agreed to continue stable dose of Interferon-β \[IFN-β\] or Glatiramer Acetate \[GA\] and consented to continue on treatment.

You may not qualify if:

• Any known condition or circumstance that would have prevented in the investigator's opinion, compliance or completion of the study
• The above information is not intended to contain all considerations relevant to patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (7)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

Vienna, Austria

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

Sanofi-Aventis Administrative Office

Guildford, United Kingdom

Location

Related Publications (2)

• 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

• Freedman MS, Wolinsky JS, Truffinet P, Comi G, Kappos L, Miller AE, Olsson TP, Benamor M, Chambers S, O'Connor PW. A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. Mult Scler J Exp Transl Clin. 2015 Dec 7;1:2055217315618687. doi: 10.1177/2055217315618687. eCollection 2015 Jan-Dec.

  PMID: 28607708 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

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

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

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

• Clinical Sciences & Operations

  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, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 19, 2008
• Study Start: October 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: December 31, 2012
• Results First Posted: December 31, 2012

Record last verified: 2012-12

Locations

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