Tecovirimat + Smallpox Vaccine for Smallpox

Recruiting at 1 trial location

Overseen By Emily Blum

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: SIGA Technologies

Must not be taking: Anticoagulants, Anticonvulsants, Antidiabetics, others

Disqualifiers: Pregnancy, Smallpox history, Obesity, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to evaluate the immunogenicity profile of JYNNEOS® when 2 doses are administered subcutaneously (SC) 4 weeks apart; and potential immunological interference while concomitantly administering TPOXX or placebo orally twice daily (BID) for 28 days.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications are prohibited within 14 days before the first vaccine injection, including some antidiabetic, anticoagulant, and anticonvulsant drugs, among others. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug Tecovirimat (TPOXX) for treating smallpox?

Tecovirimat has been shown to be effective in preventing lethal orthopoxviral disease in animal models, and all tecovirimat-treated animals survived smallpox infection in studies, suggesting it is likely to benefit humans with smallpox. Additionally, it was approved by the FDA based on its efficacy in animal models. ^{1 2 3 4 5}

How is the drug Tecovirimat + Smallpox Vaccine unique for treating smallpox?

Tecovirimat (TPOXX) is unique because it specifically targets the orthopoxvirus VP37 protein, preventing the virus from spreading in the body, and is approved for smallpox treatment based on animal studies. This combination with the JYNNEOS vaccine offers a novel approach by pairing an antiviral drug with a vaccine to enhance protection against smallpox. ^{2 5 6 7 8}

Research Team

Dennis Hruby, Ph.D.

Principal Investigator

SIGA Technologies

Eligibility Criteria

Healthy men and women aged 18-42, with normal heart rate, blood cell counts, kidney and liver function. Must not be pregnant or breastfeeding, agree to use contraception or abstain from sex during the study. Cannot have significant allergies or medical conditions that could interfere with the trial.

Inclusion Criteria

You are a healthy person between the ages of 18 and 42 years old when you agree to participate in the study.

Your heart rate is between 40 and 110 beats per minute while resting.

You do not have HIV, hepatitis B, or hepatitis C.

Exclusion Criteria

You have a history of significant medical conditions related to allergies, blood, hormones, lungs, digestion, heart, liver, brain or mental health. (Note: Seasonal allergies that are being treated or are not causing any symptoms are okay.)

Received any vaccinations within 28 days prior to Day 1 or plans to receive a vaccination at any time during the treatment period or within 28 days after Day 29

Weighs 120 kg or more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JYNNEOS subcutaneously on Day 1 and Day 29, and TPOXX or placebo orally twice daily for 28 days

4 weeks

2 visits (in-person) for JYNNEOS administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• JYNNEOS
• TPOXX

Trial Overview The trial is testing how well a smallpox vaccine (JYNNEOS) works when given alongside an oral medication (TPOXX) or placebo for 28 days. Participants will receive two doses of JYNNEOS via injection four weeks apart while taking TPOXX/placebo twice daily.

Participant Groups

Group I: JYNNEOS + TPOXX Active Control 2 Interventions

An oral dose of 600 mg (3 × 200 mg capsules) TPOXX BID (every 12 hours \[±30 minutes\]) for 28 days and a single AM SC dose of 0.5 mL JYNNEOS on Day 1 and Day 29. JYNNEOS will be administered with TPOXX concomitantly on Day 1

Group II: JYNNEOS + matching TPOXX placebo Placebo Group 2 Interventions

An oral dose of placebo (3 capsules identical to TPOXX) BID (every 12 hours \[±30 minutes\]) for 28 days and a single AM SC dose of 0.5 mL JYNNEOS on Day 1 and Day 29. JYNNEOS will be administered with TPOXX placebo concomitantly on Day 1.

Who Is Running the Clinical Trial?

SIGA Technologies

Lead Sponsor

Trials

11

Recruited

2,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Tecovirimat (TPOXX®) is an antiviral drug specifically designed to target orthopoxviruses, including the variola virus that causes smallpox, by inhibiting a key protein necessary for the virus's spread within the host.

Approved in July 2018 for treating smallpox in patients weighing 13 kg or more, tecovirimat's efficacy was demonstrated through animal studies, allowing it to gain approval under the FDA's Animal Rule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tecovirimat: First Global Approval. Hoy, SM.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preemptive Tecovirimat Use in an Active Duty Service Member Who Presented With Acute Myeloid Leukemia After Smallpox Vaccination. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tecovirimat: First Global Approval. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Co-administration of tecovirimat and ACAM2000™ in non-human primates: Effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox). [2022]

5. England pubmed.ncbi.nlm.nih.gov

An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

New Perspectives on Antimicrobial Agents: Tecovirimat for Treatment of Human Monkeypox Virus. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of Treatment Delay on Efficacy of Tecovirimat Following Lethal Aerosol Monkeypox Virus Challenge in Cynomolgus Macaques. [2023]