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Tenofovir Alafenamide for Treatment of Symptoms and Neuroprotection in Relapsing Remitting Multiple Sclerosis

NCT04880577 · Status: WITHDRAWN · Phase: PHASE2 · Type: INTERVENTIONAL

Last updated 2022-11-15

No results posted yet for this study

Summary

As the in vivo reservoir of the Epstein-Barr virus, B cells play an important role in the perpetuation of MS disease activity. B cell depletion therapy with medications like ocrelizumab or rituximab have proved very successful in preventing clinical relapses and MRI activity in MS, but incomplete in terms of neuroprotection and symptomatic outcomes. Ocrelizumab and rituximab only target naïve and memory B cells expressing the CD20 marker but do not deplete the wide spectrum of B cell lineages including plasmablasts and plasma cells, which are also key reservoirs for EBV. This is particularly relevant to the mechanism of action of TAF, since EBV lytic reactivation occurs in coordination with B-cell differentiation. In vivo, the initiation of plasma cell differentiation provides the physiological trigger for EBV lytic reactivation, and EBV utilizes the plasma cell differentiation program to replicate. As these cells are ineffectively depleted by anti-CD20 treatment, the use of TAF would be highly complementary as an add-on treatment to anti-CD20 therapy.

Anti-EBV therapy with TAF in combination with ocrelizumab or rituximab will therefore provide a synergistic approach to cover the whole EBV reservoir.

The primary aims of the proposed trial are to determine if TAF, at the standard dose of 25 mg/day administered for 12 months:

i) is safe and well-tolerated by individuals with RRMS over a period of treatment of 12 months; ii) leads to an overall improvement in fatigue, as assessed by the Modified Fatigue Impact Scale by 12 months; and iii) causes a reduction in serum concentrations of neurofilament light chain (NfL), a marker of neuronal damage in MS.

Conditions

  • Multiple Sclerosis, Relapsing-Remitting
  • Fatigue

Interventions

DRUG

TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY]

The study is designed to add on TAF to anti-CD20 therapies

DRUG

Placebo

Placebo arm

Sponsors & Collaborators

  • Gilead Sciences

    collaborator INDUSTRY

  • Massachusetts General Hospital

    lead OTHER

Principal Investigators

  • Michael Levy, MD, PhD · Massachusetts General Hospital

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-09-15
Primary Completion
2024-02-14
Completion
2025-02-14
FDA Drug
Yes

Countries

  • United States

Study Locations

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Entities

Drugs
Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04880577 on ClinicalTrials.gov