MAIN STUDY: SWITCH SUB-STUDY: SWITCH-JCV

NCT01970410 | Completed Phase 4 Results DMC

• 1 other identifier: SWITCH-001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 3

Brief Summary

MAIN STUDY: The purpose of this study is to determine if teriflunomide will be safe and effective to prevent relapses in patients with relapsing types of MS when switching from natalizumab to teriflunomide in patients at risk for PML. This is a two center interventional study of patients who have had 12 or more continuous infusions of natalizumab , who are anti-JCV-ab positive, and who had been free of clinical relapses during prior 12 months of natalizumab therapy who will be switching to teriflunomide. SUB-STUDY: To study the number of patients experiencing a reduction in the anti-JCV antibody Index value in patients who had received at least one dose of teriflunomide during participation in the SWITCH protocol (main study).

Conditions

Multiple Sclerosis

Keywords

teriflunomide; natalizumab; relapsing multiple sclerosis

Outcome Measures

Primary Outcomes (1)

• MAIN STUDY: Number of Participants Relapse Free at 24 Months

  Number of patients relapses free by month 24.

  24 months

Secondary Outcomes (3)

• MAIN STUDY: Time to Return of Radiological Evidence of Multiple Sclerosis Activity With New Gadolinium "Enhancing" (Gd+) Lesions on Cranial MRI.

  24 months

• MAIN STUDY: Expanded Disability Status Scale (EDSS) Sustained Progression for 3 Months as Measured by at Least 0.5 Increase From Baseline or 1 in Any EDSS Set Score

  24 months

• MAIN STUDY: Mean Time to New T2 or Enlarging T2 Hyperintensities on Monthly Sentinel Brain MRIs

  24 months

Study Arms (1)

Teriflunomide

EXPERIMENTAL

Teriflunomide 14 mg oral teriflunomide daily

Drug: teriflunomide

Interventions

teriflunomide DRUG

14 mg oral teriflunomide daily

Also known as: Aubagio

Teriflunomide

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female patients, age 21 to 60 with relapsing forms of MS, treated with natalizumab for 12 consecutive months or longer with anti-JCV Ab positive during that time period.
• Able to understand and sign Informed Consent Document.
• Stable disease during treatment with natalizumab. No clinical relapses for at least 12 months.
• Stable MRI on follow-up MRI scans for prior 12 months without evidence of new or enlarging T-2 hyperintensities or Gd+ lesions.
• No clinical evidence by imaging or cerebrospinal fluid (CSF) for PML.
• No evidence of significant cognitive limitation or psychiatric disorder.
• Expanded Disability Status Scale (EDSS) of 1.0 to 6.0 inclusive.

You may not qualify if:

• Any mental condition of such that patient is unable to understand the nature, scope and possible consequences of the study.
• Patients that are known HIV positive.
• Patients with a known history of hepatitis.
• Known history of active tuberculosis not adequately treated, or a positive ppd skin test or positive quantiferon gold.
• Any persistent or severe infection.
• Any malignancy within 5 years, except for Basal or Squamous cell skin lesions, which have been surgically excised, with no evidence of metastasis.
• Clinically relevant or unstable cardiovascular, neurological (i.e. progressive weakness, increasing hypesthesia), endocrine, or other major systemic diseases.
• History of drug or alcohol abuse within the past year.
• Any significant depression or psychiatric disease (BDI II greater than 25) within the past year.
• Any significant lab abnormality as deemed by the investigator including but not limited to the following:
• Hypoproteinemia with serum albumin \< 3.0g/dl.
• Serum creatinine \>133umol/L (or \>1.5 mg/dl)
• Hematocrit \<24% and/or
• Absolute white blood cell count \< 4,000 cells/mm3 (µl) and/or
• Platelet Count \<150,000 cells/mm3 (µl) and /or

Sponsors & Collaborators

• Providence Health & Services: lead
• Multiple Sclerosis Center of Northeastern New York: collaborator

Study Sites (3)

Phoenix Neurological Associates, Ltd

Phoenix, Arizona, 85018, United States

Location

Multiple Sclerosis Center of Northeastern New York

Latham, New York, 12110, United States

Location

Providence Multiple Sclerosis Center

Portland, Oregon, 97225, United States

Location

Related Publications (11)

• Gold R, Wolinsky JS. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand. 2011 Aug;124(2):75-84. doi: 10.1111/j.1600-0404.2010.01444.x. Epub 2010 Sep 29.

  PMID: 20880295 BACKGROUND

• Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Strand V, Kirschbaum BJ. Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol. 1999 Dec;93(3):198-208. doi: 10.1006/clim.1999.4777.

  PMID: 10600330 BACKGROUND

• Ruckemann K, Fairbanks LD, Carrey EA, Hawrylowicz CM, Richards DF, Kirschbaum B, Simmonds HA. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem. 1998 Aug 21;273(34):21682-91. doi: 10.1074/jbc.273.34.21682.

  PMID: 9705303 BACKGROUND

• Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.

  PMID: 16510744 BACKGROUND

• Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, Pace A, Cheung A, Chen LL, Berman M, Zein F, Wilson E, Yednock T, Sandrock A, Goelz SE, Subramanyam M. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010 Sep;68(3):295-303. doi: 10.1002/ana.22128.

  PMID: 20737510 BACKGROUND

• Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012 May 17;366(20):1870-80. doi: 10.1056/NEJMoa1107829.

  PMID: 22591293 BACKGROUND

• Miravalle A, Jensen R, Kinkel RP. Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol. 2011 Feb;68(2):186-91. doi: 10.1001/archneurol.2010.257. Epub 2010 Oct 11.

  PMID: 20937940 BACKGROUND

• Stuve O, Cravens PD, Frohman EM, Phillips JT, Remington GM, von Geldern G, Cepok S, Singh MP, Tervaert JW, De Baets M, MacManus D, Miller DH, Radu EW, Cameron EM, Monson NL, Zhang S, Kim R, Hemmer B, Racke MK. Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology. 2009 Feb 3;72(5):396-401. doi: 10.1212/01.wnl.0000327341.89587.76. Epub 2008 Nov 5.

  PMID: 18987352 BACKGROUND

• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.

  PMID: 6685237 BACKGROUND

• Cohan SL, Edwards K, Lucas L, Gervasi-Follmar T, O'Connor J, Siuta J, Kamath V, Garten L, Chen C, Thomas J, Smoot K, Kresa-Reahl K, Spinelli KJ. Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy. Mult Scler J Exp Transl Clin. 2019 Jan 16;5(1):2055217318824618. doi: 10.1177/2055217318824618. eCollection 2019 Jan-Mar.

  PMID: 30729028 RESULT

• Cohan S, Gervasi-Follmar T, Kamath A, Kamath V, Chen C, Smoot K, Baraban E, Edwards K. The results of a 24-month controlled, prospective study of relapsing multiple sclerosis patients at risk for progressive multifocal encephalopathy, who switched from prolonged use of natalizumab to teriflunomide. Mult Scler J Exp Transl Clin. 2021 Dec 16;7(4):20552173211066588. doi: 10.1177/20552173211066588. eCollection 2021 Oct.

  PMID: 34950502 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

teriflunomide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Director of PBSI /WC Clinical Research Program
• Organization: Providence Health & Services

Chiayi.Chen@providence.org

(503) 216-1012

Study Officials

• Keith R Edwards, MD

  Multiple Sclerosis Center of Northeastern New York

  STUDY DIRECTOR

• Stanley Cohan, MD, Ph. D

  Providence Multiple Sclerosis Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 28, 2013
• Study Start: October 1, 2013
• Primary Completion: April 30, 2021
• Study Completion: February 14, 2022
• Last Updated: January 30, 2023
• Results First Posted: October 20, 2022

Record last verified: 2023-01

Locations

US (3)