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Multiple Sclerosis, Relapsing-RemittingPhase 2NCT04880577

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

A Phase 2 study testing TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY] in people with Multiple Sclerosis, Relapsing-Remitting and Fatigue, run by Massachusetts General Hospital at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY]
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
15 Sep 2022to 14 Feb 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of signed and dated informed consent form
  • Stated willingness and ability to comply with all study procedures and availability for the duration of the study
  • Aged 18+ years
  • Diagnosis of MS using revised 2010 McDonald criteria of clinically definite MS.
  • Receiving treatment with either ocrelizumab or rituximab on a regular twice-yearly schedule. The first infusion must have been received at least 6 months before enrollment.
  • Must report significant fatigue during the past 3 months not due to a cause other than MS.
  • For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

Who cannot join

  • Pregnancy or lactation
  • Known allergic reactions to components of TAF
  • Treatment with another investigational drug or other MS-directed intervention such as glatiramer acetate, or dimethyl fumarate within 3 months
  • Positive HIV antibody test, active or latent hepatitis B
  • Relapse and/or steroid treatment within the previous 30 days
  • Baseline EDSS > 7
Show all 11Show fewer
  • Current symptoms of severe, progressive, or uncontrolled renal, hematologic, gastrointestinal, pulmonary, cardiac, or neurologic disease, or other medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study
  • Known history of sleep apnea, narcolepsy, or other significant sleep disorders
  • Recent changes to medications affecting sleep or fatigue or changes in dosage of those medications within 90 days
  • Creatinine clearance (CrCl) <55mL/min, as calculated by the Cockcroft-Gault equation
  • Taking medication with known interactions with tenofovir alafenamide including: Acyclovir, valacyclovir, adefovir, cabozantinib, carbamazepine, cidofovir, cladribine, cobicistat, diclofenac, multiple NSAIDs or chronic high dose NSAIDs, fosphenytoin or phenytoin, ganciclovir, valganciclovir, oxcarbazepine, phenobarbital, primidone, rifabutin, rifampin, rifapentine, sofosbuvir, tipranavir

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

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.

Read more

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

  1. 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.
Being tested
TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY], Placebo
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Fatigue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called Ocrelizumab, rituximab

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

  • PlaceboDrug

    Also called ocrelizumab, rituximab

    Placebo arm

Study groups in NCT04880577
Study groupRoleWhat they receive
TAFExperimental25 mg of daily TAF
Receives: Drug: TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY]
PlaceboPlacebo comparatorPlacebo pill
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Safety and tolerability of TAF by individuals with RRMS

    Measured: From baseline to 12 months

  2. Modified Fatigue Impact Scale

    Change in Modified Fatigue Impact Scale (MFIS) score (range 0-84, higher is more fatigue)

    Measured: From baseline to 12 months

  3. serum concentrations of neurofilament light chains (NfL)

    Reduction in serum concentrations of neurofilament light chains (NfL), a marker of neuronal damage in MS (pg/ml, the higher the more neuronal damage)

    Measured: From baseline to 12 months

Secondary outcomes (12)

  1. Multiple Sclerosis Impact Scale-29

    Change in Multiple Sclerosis Impact Scale-29 (MSIS-29) score (range 0-100, higher scores are more impactful)

    Measured: From baseline to 12 months

  2. Short Form 36 Health Survey Questionnaire

    Change in Short Form 36 (SF-36) Health Survey Questionnaire (range 0-100, higher scores are healthier)

    Measured: From baseline to 12 months

  3. Beck Depression Inventory

    Change in Beck Depression Inventory (BDI-II) score (range 0-63, higher score indicate more severe depression)

    Measured: From baseline to 12 months

  4. Perceived Deficits Questionnaire

    Change in Self-Reported Cognitive Dysfunction: Perceived Deficits Questionnaire (PDQ)(range 0-80, higher scores indicate more perceived cognitive dysfunction)

    Measured: From baseline to 12 months

  5. Annualized relapse rate

    Number of relapses per year

    Measured: From baseline to 12 months

  6. Expanded Disability Status Scale

    Change in Expanded Disability Status Scale (EDSS) score (range 0-10, higher scores are more disabled)

    Measured: From baseline to 12 months

  7. Symbol Digit Modality Test

    Change in Symbol Digit Modality Test (SDMT)

    Measured: From baseline to 12 months

  8. Timed 25 Foot Walk

    Change in Timed 25 Foot Walk Test (T25-FW) (timed in seconds, longer time is more disabled)

    Measured: From baseline to 12 months

  9. 9-Hole Peg Test

    Change in 9-Hole Peg Test (9-HPT)

    Measured: From baseline to 12 months

  10. Number of new MRI lesions

    New active MRI lesions (gadolinium-enhancing, and new or enlarging T2 lesions)

    Measured: From baseline to 12 months

  11. EBV viral load

    Change in EBV viral load in saliva

    Measured: From baseline to 12 months

  12. EBV titers

    Change in anti-EBV antibody titers

    Measured: Comparison of baseline to 6 months and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2021
  2. Study start15 Sep 2022 (estimated)
  3. Primary completion14 Feb 2024 (estimated)
  4. Study completion14 Feb 2025 (estimated)

Why it stopped: Funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04880577
Sponsor's protocol ID
2020P003311
Status last verified
Nov 2022
First submitted
30 Apr 2021
Last updated
15 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TENOFOVIR ALAFENAMIDE FUMARATE 25 Mg ORAL TABLET [VEMLIDY] in people with Multiple Sclerosis, Relapsing-Remitting and Fatigue, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: From baseline to 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04880577.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2022.

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