A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Oral ARN-75039 in Healthy Adult Subjects

NCT05735249 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: ARN-75039-101
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

ARN-75039 is proposed for the treatment of subjects with LASV infection, Lassa hemorrhagic fever, a potentially fatal human disease associated with Lassa viruses, with the most significant unmet medical need. ARN-75039-101 study was a randomized, double-blind, placebo-controlled study that assessed the safety, tolerability, and PK of escalating single and multiple doses of ARN 75039 when administered by the oral route in healthy adult subjects in six single ascending dose (SAD - Part 1) cohorts and five multiple ascending dose (MAD - Part 2) cohorts.

Conditions

Healthy Adult Participants

Keywords

Phase 1; Safety; Tolerability; Randomized; Double-Blind; Single-Ascending Dose; Multiple-Ascending Dose

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  A treatment-emergent adverse event (TEAE) was defined as any adverse event that began or worsened after administration of the study drug (ARN-75039 or placebo) through the End-of-Study visit.

  From first dose through the End-of-Study (EOS) visit: Part 1 (SAD), through Day 15/EOS; Food-effect cohort, through the second treatment period and Day 29/EOS; Part 2 (MAD), from Day 1 through Day 39/EOS.

• Incidence of Treatment-Emergent Serious Adverse Events (TESAEs)

  Number of participants with at least one treatment-emergent Serious adverse event (TESAE). A TESAE is any adverse event that starts or worsens after administration of study drug (ARN-75039 or placebo).

  From first dose through the End-of-Study (EOS) visit: Part 1 (SAD), through Day 15/EOS; Food-effect cohort, through the second treatment period and Day 29/EOS; Part 2 (MAD), from Day 1 through Day 39/EOS.

Secondary Outcomes (7)

• Part 1-SAD: Cmax

  Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose.

• Part 1-SAD: Tmax

  Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose.

• Part 1-SAD: Terminal Half-life

  Derived from plasma samples collected from Day 1 predose through 336 hours (Day 15/EOS) postdose.

• Part 1-SAD: AUC

  Day 1 predose and at 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 12, 24 (Day 2), 48 (Day 3), 72 (Day 4), 168 (Day 8), and 336 (Day 15/EOS) hours postdose.

• Part 2-MAD: Cmax0-10h

  Day 1 and Day 10: predose and at 0.5, 1, 2, 4, 6, 8, and 10 hours after the morning dose.

Study Arms (2)

ARN-75039 oral capsules

EXPERIMENTAL

Escalating single or multiple doses of ARN-75039 oral capsules

Drug: ARN-75039 oral capsules

Placebo (microcrystalline cellulose)

PLACEBO COMPARATOR

Specified weight of placebo (microcrystalline cellulose) corresponding to the dose of ARN-75039 within the same cohort and encapsulating it in a HPMC capsule prior to dosing.

Drug: Placebo

Interventions

ARN-75039 oral capsules DRUG

active oral study drug prepared and administered as oral capsules

Also known as: ARN75039

ARN-75039 oral capsules

Placebo DRUG

Given at frequency and amounts matching ARN- 75039 dosing regimen

Also known as: Matching placebo oral capsules (Cohorts 1 through 11)

Placebo (microcrystalline cellulose)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is male or female, age 18 to 55 years, inclusive, at Screening.
• Body mass index (BMI) between 18.5 and 35 kg/m2, inclusive, at Screening.
• In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Day -1 or 1.
• Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the laboratory reference range at Screening; subjects with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities.
• Estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥ 80 mL/min/1.73m2 at Screening
• Females of childbearing potential must practice effective contraception per national regulatory guidelines for clinical trials from Screening, throughout the study and for 28 days after the EOS visit.
• Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone (FSH) to confirm post-menopausal status (as verified by an FSH of ≥40). Surgically sterile females are eligible; however, proof via medical records will be required.
• Males must agree to not donate sperm and/or to use condoms during sexual intercourse from the time of the first study drug administration and for 90 days following the last dose of study drug, and females must agree not to donate eggs from the time of the first study drug administration and for 60 days following the last dose of study drug.
• Must be Willing and able to comply with measures to avoid photosensitivity reactions (i.e., avoidance of outdoor sun exposure and tanning; consistent use of long sleeve shirts, long pants, hats, and sunglasses; consistent use of SPF 75 or greater sunscreen when outdoors) from Day 1 through Day 8 in Part 1 and through Day 25 in Part 2.
• Able to provide informed consent.
• Willing and able to comply with this protocol and be available for the entire duration of the study.

You may not qualify if:

• Any clinically significant underlying illness in the opinion of the Investigator.
• Poor venous access.
• Inability to ingest all capsules of a multi-capsule dose within 5 minutes of ingestion of the first capsule.
• Prior exposure to ARN-75039.
• Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) at Screening; subjects with adequately treated HCV are eligible for enrollment.
• Positive test for SARS-CoV-2 infection on Day -1.
• Consumption of Seville oranges, grapefruit or grapefruit juice within 72 hours prior to Day 1 or during the study.
• History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Day -1.
• Use of any prescription or over-the-counter (OTC) medications, including food supplements, vitamins, herbal medications (e.g., St. John's wort), and cannabis, with the exception of contraceptive medications and as needed (prn) acetaminophen or paracetamol (not exceeding 2 grams/day) within 7 days prior to study drug administration and through the EOS visit.
• History of malignancy, except adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix.
• Smoking greater than 20 cigarettes, cigars, cigarillos or E-cigarettes per week in the 3 months prior to study drug administration or during the study.
• Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and safety follow-up period.
• Any reason or condition that, in the investigator's opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results.
• A QT duration corrected for heart rate by Fridericia's formula (QTcF) \> 450 millisecond (msec) based on either single or averaged QTcF values of triplicate ECGs obtained over a 3-minute interval (at Screening).
• Blood product donation within 30 days before Screening.

Sponsors & Collaborators

• Arisan Therapeutics, Inc.: lead
• United States Department of Defense: collaborator

Study Sites (1)

Spaulding Clinical, LLC

West Bend, Wisconsin, 53095, United States

Location

Limitations and Caveats

Phase 1 safety and pharmacokinetic study in healthy adults; not designed to assess efficacy.

Results Point of Contact

• Title: Kenneth McCormack, PhD
• Organization: Arisan Therapeutics

kenm@arisanthera.com

858-766-0495

Study Officials

• Ken McCormack, PhD

  Arisan Therapeutics, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Central, computer-generated randomization scheme
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and PK of escalating single and multiple doses of ARN-75039 when administered by the oral route in healthy adult subjects. Six single ascending dose (SAD) cohorts and five multiple ascending dose (MAD) cohorts, with approximately 8 subjects per cohort, will be enrolled to receive study drug or placebo. Within each cohort, the first 2 subjects will be randomized 1:1 to receive ARN-75039 capsules or placebo. After a review of the first 3 days of blinded safety for these subjects by the Medical Monitor, an additional 6 subjects were randomized in a 5:1 (active: placebo) ratio. Each subsequent dose escalation was based on safety data review of the current dose level.

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 21, 2023
• Study Start: January 23, 2023
• Primary Completion: March 28, 2025
• Study Completion: March 28, 2025
• Last Updated: May 1, 2026
• Results First Posted: May 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)