Effects of Antiviral Therapies on Epstein-Barr Virus Replication

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Primary Purpose

Status

Enrolling by invitation

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Truvada (tenofovir/emtricitabine)

About this trial

This is an interventional basic science trial for Multiple Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Age: 18+ Established diagnosis of multiple sclerosis Evidence of Epstein Barr virus (EBV) infection by serological testing for EBV antibodies antibodies (subjects will have EBV testing performed at the pre-screening visit and if serologies are negative, the subjects will be removed from the study) Exclusion Criteria: Pregnancy or lactation Known allergic reactions to components of Truvada Previous treatment with Truvada or Descovy Unknown HIV status (subjects must have completed HIV antigen/antibody and viral load testing within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit) Active or latent hepatitis B (HBV) (subjects must have completed HBV serologies - HbsAg, anti-HBs, and anti-HBc - within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit) 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 Creatinine clearance (CrCl) <75mL/min, as calculated by the Cockcroft-Gault equation Urine dipstick for protein and glucose, excluding values of "1 +" or greater Any history of bone fractures not explained by trauma Confirmed Grade 2 or greater hypophosphatemia Any Grade 2 or greater toxicity on screening tests and assessments Taking a medication with known interactions with Truvada including but not limited to: Acyclovir, valacyclovir, adefovir, cabozantinib, carbamazepine, cidofovir, cladribine, cobicistat, diclofenac, multiple non-steroidal antiinflammatories (NSAIDs) or chronic high dose NSAIDs, fosphenytoin or phenytoin, ganciclovir, valganciclovir, oxcarbazepine, phenobarbital, primidone, rifabutin, rifampin, rifapentine, sofosbuvir, tipranavir, or other drugs that significantly affect renal function Current treatment with drugs known to affect EBV replication as listed below: Acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, teriflunomide, interferon

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment arm

Arm Description

After a one-month baseline period where patients will not take any study drug, all patients will receive Truvada (tenofovir/emtricitabine) for three months. The study drug will be Truvada (tenofovir/emtricitabine), an antiviral drug that is approved by the Food & Drug Administration (FDA) for the treatment of chronic hepatitis B virus and for the treatment and prevention of human immunodeficiency virus (HIV) infection. The study drug will be administered at the standard dose used for the treatment and prevention of HIV (300mg tenofovir disoproxil fumarate, 200mg emtricitabine). Since extensive safety and tolerability data already exists for this standard dose, the selection of this dose also allows us to use existing data to inform strategies for safety and tolerability monitoring to minimize risk, as detailed in the study design.

Outcomes

Primary Outcome Measures

Epstein Barr virus (EBV) viral load

EBV viral load will be quantified in saliva and peripheral blood using a sensitive assay.

Secondary Outcome Measures

Tolerability of Truvada (tenofovir/emtricitabine)

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Fatigue

Fatigue will be measured using a standardized survey scale where higher scores indicate more fatigue

Full Information

NCT ID

NCT05957913

First Posted

June 28, 2023

Last Updated

July 14, 2023

Sponsor

Massachusetts General Hospital

Collaborators

Solving MS

1. Study Identification

Unique Protocol Identification Number

NCT05957913

Brief Title

Effects of Antiviral Therapies on Epstein-Barr Virus Replication

Official Title

Effects of Antiviral Therapies on Epstein-Barr Virus Replication

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

June 5, 2023 (Actual)

Primary Completion Date

June 4, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Solving MS

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Product Manufactured in and Exported from the U.S.

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

This research study is being performed to find out if Truvada (tenofovir/emtricitabine), an antiviral drug with activity against the Epstein Barr virus (EBV), can reduce EBV levels in saliva and blood in people with multiple sclerosis (MS). A second goal is to find out if Truvada (tenofovir/ emtricitabine) is safe and tolerable in people with MS.

Detailed Description

The proposed trial is built on the premise that multiple sclerosis (MS) is, in part, triggered by infection with the human herpesvirus Epstein Barr virus (EBV), and that targeting the virus could be a more effective and safer strategy for MS treatment than immunomodulation or immunosuppression alone. The evidence supporting a causal role for EBV in MS initially came from epidemiological studies that showed similarities in the distribution of infectious mononucleosis and MS, a 2-3 fold increased MS risk among individuals with a clinical history of infectious mononucleosis, and by compelling evidence that MS rarely, if ever, develops in individuals who are not infected with EBV. Furthermore, in a longitudinal study based on the Department of Defense Serum Repository with samples from over 7 million young adults free of MS, individuals who were EBV-seronegative at baseline did not develop symptoms of MS until at least several months after EBV seroconversion, and high serum antibody titers against the EBV-encoded nuclear antigen-1 were associated with an over 30-fold increase in MS risk. Antiviral agents repurposed from treating other herpesviruses, like acyclovir or valacyclovir, have had minimal clinical efficacy against EBV in studies for infectious mononucleosis and multiple sclerosis. Prodrugs of tenofovir, such as tenofovir disoproxil fumarate (TDF), are significantly more potent inhibitors of EBV replication in cell culture than other drugs that have been clinically ineffective for EBV. TDF is a safe drug used clinically for HIV pre-exposure prophylaxis (PrEP) in HIV-negative patients as the drug Truvada. Truvada has been widely used since its approval in 2004 for the treatment of human immunodeficiency virus (HIV), and has a well-known safety profile that makes it a good candidates for clinical studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

The study design will be an open-label single arm study.

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment arm

Arm Type

Experimental

Arm Description

After a one-month baseline period where patients will not take any study drug, all patients will receive Truvada (tenofovir/emtricitabine) for three months. The study drug will be Truvada (tenofovir/emtricitabine), an antiviral drug that is approved by the Food & Drug Administration (FDA) for the treatment of chronic hepatitis B virus and for the treatment and prevention of human immunodeficiency virus (HIV) infection. The study drug will be administered at the standard dose used for the treatment and prevention of HIV (300mg tenofovir disoproxil fumarate, 200mg emtricitabine). Since extensive safety and tolerability data already exists for this standard dose, the selection of this dose also allows us to use existing data to inform strategies for safety and tolerability monitoring to minimize risk, as detailed in the study design.

Intervention Type

Drug

Intervention Name(s)

Truvada (tenofovir/emtricitabine)

Other Intervention Name(s)

TDF

Intervention Description

Doses and route of administration of the study drug will be kept the same as for the FDA-approved indication of HIV-1 prevention in healthy individuals. The study drug is not FDA-approved for the treatment of multiple sclerosis.

Primary Outcome Measure Information:

Title

Epstein Barr virus (EBV) viral load

Description

EBV viral load will be quantified in saliva and peripheral blood using a sensitive assay.

Time Frame

Change from baseline at three months

Secondary Outcome Measure Information:

Title

Tolerability of Truvada (tenofovir/emtricitabine)

Description

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time Frame

Change from baseline at three months

Title

Fatigue

Description

Fatigue will be measured using a standardized survey scale where higher scores indicate more fatigue

Time Frame

Change from baseline at three months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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 Age: 18+ Established diagnosis of multiple sclerosis Evidence of Epstein Barr virus (EBV) infection by serological testing for EBV antibodies antibodies (subjects will have EBV testing performed at the pre-screening visit and if serologies are negative, the subjects will be removed from the study) Exclusion Criteria: Pregnancy or lactation Known allergic reactions to components of Truvada Previous treatment with Truvada or Descovy Unknown HIV status (subjects must have completed HIV antigen/antibody and viral load testing within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit) Active or latent hepatitis B (HBV) (subjects must have completed HBV serologies - HbsAg, anti-HBs, and anti-HBc - within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit) 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 Creatinine clearance (CrCl) <75mL/min, as calculated by the Cockcroft-Gault equation Urine dipstick for protein and glucose, excluding values of "1 +" or greater Any history of bone fractures not explained by trauma Confirmed Grade 2 or greater hypophosphatemia Any Grade 2 or greater toxicity on screening tests and assessments Taking a medication with known interactions with Truvada including but not limited to: Acyclovir, valacyclovir, adefovir, cabozantinib, carbamazepine, cidofovir, cladribine, cobicistat, diclofenac, multiple non-steroidal antiinflammatories (NSAIDs) or chronic high dose NSAIDs, fosphenytoin or phenytoin, ganciclovir, valganciclovir, oxcarbazepine, phenobarbital, primidone, rifabutin, rifampin, rifapentine, sofosbuvir, tipranavir, or other drugs that significantly affect renal function Current treatment with drugs known to affect EBV replication as listed below: Acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, teriflunomide, interferon

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Levy, MD, PhD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Multiple Sclerosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial