NCT04880577

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

Withdrawn Phase 2 Last updated 15 November 2022

What this trial tests

Phase 2 trial testing TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY] in Multiple Sclerosis, Relapsing-Remitting. Withdrawn.

Timeline

15 September 2022

Primary endpoint
14 February 2024

14 February 2025

Quick facts

Lead sponsor	Massachusetts General Hospital
Phase	Phase 2
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Start date	15 September 2022
Primary completion	14 February 2024
Estimated completion	14 February 2025
Sites	1 location across United States

Drugs / interventions tested

• TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY]
• Placebo

Conditions studied

• Multiple Sclerosis, Relapsing-Remitting — all drugs for Multiple Sclerosis, Relapsing-Remitting →
• Fatigue — all drugs for Fatigue →

Sponsor

Massachusetts General Hospital

Who can join

18 and older, any sex, with Multiple Sclerosis, Relapsing-Remitting or Fatigue. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Epstein-Barr virus and multiple sclerosis.
   Soldan SS, Lieberman PM. · · 2023 · cited 296× · PMID 35931816 · DOI 10.1038/s41579-022-00770-5
2. Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells.
   Schroeter CB, Huntemann N, Bock S, Nelke C, et al · · 2021 · cited 8× · PMID 34691057 · DOI 10.3389/fimmu.2021.747143
3. From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment.
   Raghib MF, Bernitsas E. · · 2023 · cited 4× · PMID 38002068 · DOI 10.3390/biomedicines11113069