Safety, Tolerability and Pharmacokinetics of TPOXX When Administered Orally for 28 Days

NCT04971109 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SIGA-246-024
• Study Type: interventional
• Target: 467
• Locations: 1 country
• Sites: 9

Brief Summary

This is a study to assess the safety, tolerability, and PK of oral TPOXX 600 mg when administered twice daily (BID) for 28 days in adult subjects.

Conditions

Smallpox

Outcome Measures

Primary Outcomes (4)

• Cmin

  Cmin - Minimum TPOXX concentration in plasma

  28 days

• Cmax

  Peak exposure when administered TPOXX

  28 days

• AUC(0-last) - Total Systemic TPOXX Exposure

  Total systematic exposure when administered TPOXX

  28 days

• Time To Maximum TPOXX Exposure

  Median hours post dose when administered TPOXX

  28 days

Secondary Outcomes (1)

• Adverse Events

  58 Days

Study Arms (2)

TPOXX

ACTIVE COMPARATOR

Treatment Group 1: An oral dose of 600 mg (3 x 200 mg capsules)TPOXX

Drug: TPOXX

TPOXX Placebo

PLACEBO COMPARATOR

Treatment Group 2: An oral dose of placebo (3 capsules identical to TPOXX)

Other: TPOXX Placebo

Interventions

TPOXX DRUG

Study is based on Animal Regulatory Rule

Also known as: tecovirimat

TPOXX

TPOXX Placebo OTHER

Does not apply

Also known as: Placebo

TPOXX Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is male or female between 18 and 80 years of age, inclusive.
• Subject is available for clinical follow-up for the duration of the study.
• Women of childbearing potential have a negative beta human chorionic gonadotropin pregnancy test (serum) at the screening visit and a confirmatory negative pregnancy test on Day 1 or Day -1 (PK subset) before receipt of study drug, and meet one of the following criteria:
• Subject or their partner has undergone surgical sterilization.
• Subject is postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause and has a documented plasma follicle stimulating hormone level \>40 IU/mL.
• Subject agrees to be abstinent (ie, heterosexually inactive) for the duration of the study.
• Subject agrees to consistently use 1 of the following methods of contraception from the beginning of screening (which they had been consistently using for at least 30 days before the first dose of study drug) through 30 days after the last dose of study drug:
• i. Condoms, male or female, with a spermicide NOTE: For male subjects, condoms must be used for 90 days after the last dose of study drug. Male and female condoms should not be used together, as this can reduce their effectiveness.
• ii. Diaphragm or cervical cap with spermicide iii. Intrauterine device with spermicide iv. Oral contraceptives or other hormonal methods NOTE: Another nonhormonal method of contraception must be used in conjunction with oral contraceptives.
• v. Male sexual partner who had undergone a vasectomy at least 3 months before screening
• Male subjects must agree to not donate sperm from the first dose of study drug through 90 days after the last dose of study drug.
• Subject is considered by the investigator to be in good general health as determined by medical history (no hospitalizations for chronic medical conditions in the previous 2 years), clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.
• Subject agrees not to use nicotine products, including electronic vapor cigarettes, nicotine patches, or nicotine gum, for at least 30 days before the Day 1 randomization visit through completion of the Day 29 dosing complete/early termination (ET) visit.
• Subject agrees to comply with the study dietary requirements throughout the study drug dosing period.
• Subject agrees not to consume caffeine- or xanthine-containing products during all study visits, including overnight stays (PK subset); sodas, coffee, and tea designated as caffeine free or noncaffeinated may be consumed on study days; caffeine may be consumed while at home and between study visits.

You may not qualify if:

• Subject is a female who is pregnant or breastfeeding or planning to become pregnant within 3 months after the last dose of study drug.
• Subject has a history of any clinically significant conditions including:
• 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 mmHg diastolic)
• Thyroidectomy or thyroid disease that required medication within the past 12 months
• Serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years
• History of head trauma resulting in a diagnosis of traumatic brain injury other than concussion
• Frequent episodes of headache
• Subject has received any vaccination 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 study Day 28.
• Subject has received treatment in another clinical study of an investigational drug (or medical device) or investigational vaccine within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
• Subject has a history of relevant drug and/or food allergies (ie, allergy to TPOXX or excipients, or any significant food allergy that could preclude a standard diet in the clinical investigative site).
• Subject has any condition possibly affecting drug absorption (eg, previous surgery on the gastrointestinal tract, including removal of parts of the stomach, bowel, liver, gallbladder, or pancreas, with the exception of appendectomy).
• Subject has evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of the first dose of study drug), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. Exceptions to these criteria (eg, stable, mild joint disease unassociated with collagen vascular disease) may be made following discussions with the medical monitor.
• Subject has a history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or risk factors for torsades de pointes (eg, heart failure, hypokalemia).

Sponsors & Collaborators

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

Study Sites (9)

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Advanced Pharma

Miami, Florida, 33147, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Meridian Clinical Research

Omaha, Nebraska, 68134-3664, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Smallpox

Interventions

tecovirimat

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Emily Blum, Director of Clinical Development
• Organization: SIGA Technologies

eblum@siga.com

541-224-1305

Study Officials

• Dennis Hruby

  SIGA Technologies

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: An oral dose of placebo (3 capsules identical to TPOXX)
• 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 21, 2021
• Study Start: March 29, 2022
• Primary Completion: May 12, 2023
• Study Completion: May 12, 2023
• Last Updated: December 27, 2024
• Results First Posted: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)