Tecovirimat + Smallpox Vaccine for Smallpox

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of the smallpox vaccine JYNNEOS when combined with the oral medication TPOXX, an antiviral drug. Researchers aim to determine if TPOXX affects the body's response to the vaccine, administered in two doses, 4 weeks apart. Participants will receive either TPOXX or a placebo (a non-active pill) along with the vaccine. Healthy individuals who have not previously received a smallpox or similar vaccine are suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that JYNNEOS and TPOXX are generally well-tolerated by patients.

JYNNEOS, a vaccine for smallpox and monkeypox, most commonly causes tiredness, headache, and muscle pain in 34%, 28%, and 22% of cases, respectively. Serious side effects were rare in studies involving over 7,000 participants. This vaccine uses a virus that does not multiply in the body, which typically enhances its safety.

TPOXX, a treatment for smallpox, has been tested in various studies. Although specific side effects are not detailed, the FDA has approved TPOXX for smallpox, indicating a well-established safety record.

Overall, using JYNNEOS and TPOXX together in clinical trials appears safe based on past research. Participants mostly experience mild and temporary side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of JYNNEOS and TPOXX for smallpox because it offers a dual approach that could enhance protection against the virus. Unlike existing smallpox treatments that typically rely on vaccination alone, this combination includes TPOXX, an antiviral medication that inhibits the spread of the virus in the body. By pairing JYNNEOS, a modern, non-replicating vaccine, with TPOXX, there’s potential not only for preventive immunity but also for active treatment in the event of exposure. This dual-action strategy is particularly promising in providing comprehensive defense against smallpox outbreaks.

What evidence suggests that this trial's treatments could be effective for smallpox?

Research has shown that JYNNEOS, a vaccine for smallpox and mpox, works well. For those receiving both doses, the vaccine is 66% to 89% effective in preventing mpox, offering strong protection against related viruses. In this trial, some participants will receive JYNNEOS with a TPOXX placebo.

Tecovirimat, also known as TPOXX, has shown effectiveness against various viruses in animal studies. However, some human studies did not find it significantly reduced virus levels or improved health outcomes compared to a placebo. Despite this, it remains potentially helpful due to its broad activity against these viruses. In this trial, other participants will receive both JYNNEOS and TPOXX. ^{1 5 6 7 8}

Who Is on the Research Team?

Dennis Hruby, Ph.D.

Principal Investigator

SIGA Technologies

Are You a Good Fit for This Trial?

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

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

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

Your platelet count is not too low.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7422a3.htm

Use of JYNNEOS (Smallpox and Mpox Vaccine, Live ... ACIP recommended the use of JYNNEOS (a live, replication-deficient vaccinia virus vaccine) for persons aged ≥18 years at risk for mpox during an mpox outbreak.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11420512/

Effectiveness of a single dose of JYNNEOS vaccine in real world Only the VE in completely immunized men reduced to 58.7% when VE in individuals between the ages of 18 and 49 was taken into account. This may ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2215201

Vaccine Effectiveness of JYNNEOS against Mpox Disease ... The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection.

4. jynneos.com jynneos.com/

JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Non ... Data from 3 case-control studies suggest the vaccine effectiveness of JYNNEOS against mpox ranges from 66-89% for full (2 doses) vaccination.

5. tandfonline.com tandfonline.com/doi/full/10.1080/22221751.2024.2387442

Global perspectives on smallpox vaccine against monkeypox Currently, studies have reported a 35%–85% effectiveness of the smallpox vaccine in preventing mpox, with a low incidence of adverse events [Citation19,Citation ...

6. va.gov va.gov/formularyadvisor/DOC_PDF/FAQ_VA_Monkeypox_vaccine_and_therapeutic_FAQ_V4_Oct_1_2022_Update.pdf

JYNNEOS and TPOXX for Monkeypox VHA PBM ... Systemic adverse events included fatigue (34%), headache (28%), myalgia (22%), nausea (10%), chills (1%) and fever (0.5%). ▫ Study 5 evaluated ...

7. fda.gov fda.gov/media/160774/download

EMERGENCY USE AUTHORIZATION OF JYNNEOS ( ... The integrated analyses of serious adverse events (SAEs) pooled safety data across 22 studies, which included a total of 7,093 smallpox vaccine- ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04957485?term=Jynneos%20OR%20smallpox%20and%20monkeypox%20vaccine,%20live,%20non-replicating%20OR%20smallpox%20and%20mpox%20vaccine&rank=5

Study to Assess the Safety and Immunogenicity of TPOXX® ... This study is designed to evaluate the immunogenicity profile of JYNNEOS when 2 doses are administered subcutaneously (SC) 4 weeks apart.