MAIN STUDY: SWITCH SUB-STUDY: SWITCH-JCV

• Register: ClinicalTrials.gov
• Last refreshed on: 6 February 2023
• Main ID: NCT01970410
• Date of registration: 22/10/2013
• Prospective Registration: No
• Primary sponsor: Providence Health & Services
• Public title: MAIN STUDY: SWITCH SUB-STUDY: SWITCH-JCV
• Scientific title: MAIN STUDY: Switching Relapsing Multiple Sclerosis Patients Treated With Natalizumab at Risk for Progressive Multifocal Leukoencephalopathy to Teriflunomide: Is This Safe and Effective? SUB-STUDY: Analysis of JCV Antibody Index in MS Patients Treated With Teriflunomide
• Date of first enrolment: October 2013
• Target sample size: 55
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01970410
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Stanley Cohan, MD, Ph. D
• Affiliation: Providence Multiple Sclerosis Center

• Name: Keith R Edwards, MD
• Affiliation: Multiple Sclerosis Center of Northeastern New York

Key inclusion & exclusion criteria

MAIN STUDY

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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:

1. Hypoproteinemia with serum albumin < 3.0g/dl.

2. Serum creatinine >133umol/L (or >1.5 mg/dl)

3. Hematocrit <24% and/or

4. Absolute white blood cell count < 4,000 cells/mm3 (µl) and/or

5. Platelet Count <150,000 cells/mm3 (µl) and /or

6. Absolute neutrophil < 1,500 cells/mm3 (µl)

7. Liver function impairment or persisting elevations of serum glutamate pyruvate
transaminase (SGPT)/ Alanine transaminase (ALT), serum glutamate oxaloacetate
transaminase (SGOT)/ aspartate aminotransferase (AST), or direct bilirubin
greater than 1.5 fold the upper limit of normal.

- Any confounding illness or other diseases of the spine or bone that would impair
evaluation of the patient or treatment effects.

- Any clinical, CSF or MRI evidence for PML.

- Prior treatment with immunosuppressive drugs except for past use of intravenous
steroids to treat MS relapses.

- Pregnant or breast feeding women.

- Women of childbearing potential not protected by effective contraceptive method of
birth control and/or are unwilling or unable to be tested for pregnancy.

- In the conception of a child during the course of the trial.

- Known history of hypersensitivity to teriflunomide or leflunomide.

- Persisting elevations (confirmed by retest) of serum amylase or lipase greater than
2-fold the upper limit of normal.

- Known history of chronic pancreatic disease or pancreatitis.

- Prior use within 4 weeks before randomization or concomitant use of phenytoin,
warfarin, tolbutamide, cholestyramine, or products containing St. John's Wort

SUB-STUDY

Eligibility Criteria for JCV sub-study:

- Must have been enrolled in the SWITCH protocol and received at least 1 dose of 14mg
TFM during the study period.

- Must be willing to sign written, informed consent for this JCV sub-study and follow
protocol requirements.



Age minimum: 21 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: teriflunomide

Primary Outcome(s)

MAIN STUDY: Number of Participants Relapse Free at 24 Months [Time Frame: 24 months]

Secondary Outcome(s)

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 [Time Frame: 24 months]

MAIN STUDY: Time to Return of Radiological Evidence of Multiple Sclerosis Activity With New Gadolinium "Enhancing" (Gd+) Lesions on Cranial MRI. [Time Frame: 24 months]

MAIN STUDY: Mean Time to New T2 or Enlarging T2 Hyperintensities on Monthly Sentinel Brain MRIs [Time Frame: 24 months]

Secondary ID(s)

SWITCH-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Multiple Sclerosis Center of Northeastern New York

Results

• Results available: Yes
• Date Posted: 20/10/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01970410