Study to Assess the Safety and Immunogenicity of TPOXX® When Administered Orally for 28 Days With JYNNEOS

NCT04957485 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SIGA-246-028
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Smallpox

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Number of participants with adverse events when TPOXX or TPOXX Placebo is coadministered with JYNNEOS

  59 Days

• Immunogenicity

  Least squared geometric mean

  Day 43

Study Arms (2)

JYNNEOS + TPOXX

ACTIVE COMPARATOR

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

Drug: Tecovirimat; Drug: Smallpox and Mpox Vaccine

JYNNEOS + matching TPOXX placebo

PLACEBO COMPARATOR

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.

Drug: Smallpox and Mpox Vaccine; Other: Placebo

Interventions

Tecovirimat DRUG

oral antiviral

Also known as: TPOXX

JYNNEOS + TPOXX

Smallpox and Mpox Vaccine DRUG

vaccine

Also known as: JYNNEOS

JYNNEOS + TPOXX; JYNNEOS + matching TPOXX placebo

Placebo OTHER

TPOXX Placebo

JYNNEOS + matching TPOXX placebo

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Each subject must meet all of the following criteria to be enrolled in this study:
• Subject is a healthy male or female between 18 and 42 years of age, inclusive, at the time of informed consent.
• Subject has a resting heart rate \>40 beats per minute (bpm) or \<110 bpm at screening.
• Subject has negative test for HIV antibodies, hepatitis B surface antigen, and hepatitis C virus antibody.
• Subject has white blood cells ≥2500/mm3 and \<11,000/mm3.
• Subject has hemoglobin within normal limits.
• Subject has platelets ≥ lower normal limits.
• Subject has adequate renal function defined as a calculated creatinine clearance \>60 mL/min as estimated by the Cockcroft-Gault equation.
• Creatinine in males ≤1.7 mg/dL and in females ≤1.4 mg/dL (1.3 times the upper laboratory reference range).
• Subject has adequate hepatic function in the absence of other evidence of significant liver disease defined as:
• Total bilirubin \<1.5 times above the upper laboratory reference range
• Alanine aminotransferase \<1.5 times above the upper laboratory reference range
• Aspartate aminotransferase \<1.5 times above the upper laboratory reference range
• Alkaline phosphatase \<1.5 times above the upper laboratory reference range.
• Male subject has a QT interval corrected using Fridericia's formula (QTcF) \<450 ms or female subject has a QTcF \<470 ms at screening or Day 1.

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Subject is a female who is pregnant or breastfeeding or planning to become pregnant within 3 months after the second JYNNEOS injection.
• Subject has a history or suspected exposure of smallpox, monkeypox or cowpox disease, or previous vaccination with any poxvirus-based vaccine.
• Subject has 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.
• Subject weighs 120 kg or more.
• Subject has been administered or plans to be administered immunoglobulins and/or any blood products during a period starting from 3 months prior to administration of the vaccine and ending at trial conclusion.
• Subject has used any investigational or nonregistered drug or vaccine other than the trial vaccines within 28 days preceding the first dose of the trial vaccine or planned administration of such a drug /vaccine during the trial period, including the COVID-19 vaccine prior to marketing approval by the FDA.
• Subject has a known or suspected history of smallpox vaccination defined as visible vaccination scar or documentation of smallpox vaccination or as reported by the subject.
• Subject has had a previous anaphylactic reaction, severe systemic response, or serious hypersensitivity to a prior immunization.
• Subject has a history of any clinically significant conditions including the following:
• Asthma treated with oral systemic steroids within the past 6 months
• Diabetes mellitus (type 1 or 2), with the exception of gestational diabetes
• Hypertension that is poorly controlled (repeat readings \>140 mm Hg systolic and/or \>90 mm Hg diastolic)
• Serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years
• Head trauma resulting in a diagnosis of traumatic brain injury other than concussion

Sponsors & Collaborators

• SIGA Technologies: lead
• United States Department of Defense: collaborator

Study Sites (2)

Meridian Clinical Research

Omaha, Nebraska, 68134-3664, United States

Location

Aventiv Research Inc

Columbus, Ohio, 43213-6510, United States

Location

MeSH Terms

Conditions

Smallpox

Interventions

tecovirimat; Smallpox Vaccine; smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Dennis Hruby, Ph.D.

  SIGA Technologies

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 12, 2021
• Study Start: April 5, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)