FiH Study to Assess Safety and PK of SAD and MAD of ANT3310 Alone and in Combination With Meropenem in Healthy Subjects

NCT05905913 | Completed Phase 1

• 1 other identifier: ANT3310-1001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single and multiple intravenous ascending doses of ANT3310, a novel, specific, competitive inhibitor of serine β-lactamases, alone and in combination with meropenem in healthy subjects.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Number and severity of Treatment Emergent Adverse Events (TEAE) to evaluate the safety and tolerability profile of single and multiple intravenous ascending doses of ANT3310 alone (Part A and B) and in combination with meropenem (Part C)

  Percentage of subjects who experience at least one TEAE, including abnormalities in vital signs, physical examinations, laboratory safety tests and ECG, by seriousness, intensity, and relatedness

  up to 11 days

Secondary Outcomes (13)

• Part A (SAD): Maximum Plasma Concentration (Cmax) of single i.v. ascending doses of ANT3310 alone

  24 hours

• Part A (SAD): Area under the concentration time curve (AUC) of single i.v. ascending doses of ANT3310 alone

  24 hours

• Part A (SAD): Time to maximum plasma concentration (Tmax) of single i.v. ascending doses of ANT3310 alone

  24 hours

• Part A (SAD): Half-time (t1/2) of single i.v. ascending doses of ANT3310 alone

  24 hours

• Part B (MAD): Maximum Plasma Concentration (Cmax) of multiple i.v. ascending doses of ANT3310 alone

  Day 1, Day 7

Study Arms (6)

Part A: Single Intravenous Ascending Dose of ANT3310

EXPERIMENTAL

Drug: ANT3310

Part A: Single Intravenous Dose of Matching placebo

PLACEBO COMPARATOR

Drug: ANT3310-placebo

Part B: Multiple Intravenous Ascending Doses of ANT3310

EXPERIMENTAL

Drug: ANT3310

Part B: Multiple Intravenous Ascending Doses of Matching Placebo

PLACEBO COMPARATOR

Drug: ANT3310-placebo

Part C: ANT3310 + Meropenem

EXPERIMENTAL

Participants will receive a single intravenous dose of ANT3310 or Meropenem in one of the 2 treatment sequences followed by the repeat administrations of ANT3310 + Meropenem.

Drug: ANT3310; Drug: Meropenem

Part C: ANT3310 Placebo + Meropenem Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of ANT3310-placebo or Meropenem-placebo in one of the 2 treatment sequences followed by repeat administrations of ANT3310-placebo + Meropenem-placebo

Drug: ANT3310-placebo; Drug: Meropenem-placebo

Interventions

ANT3310 DRUG

ANT3310 will be infused over 3 hours

Part A: Single Intravenous Ascending Dose of ANT3310

ANT3310-placebo DRUG

ANT3310-placebo will be infused over 3 hours

Part A: Single Intravenous Dose of Matching placebo

Meropenem DRUG

Meropenem will be infused over 3 hours as a single dose as part of the drug-drug interaction study, then every 8 hours as part of the repeat doses study.

Part C: ANT3310 + Meropenem

Meropenem-placebo DRUG

Meropenem-placebo will be infused over 3 hours as a single dose as part of the drug-drug interaction study, then every 8 hours as part of the repeat doses study.

Part C: ANT3310 Placebo + Meropenem Placebo

Eligibility Criteria

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

You may qualify if:

• Participant capable of giving signed informed consent
• Contraceptive use by women or men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Participants are overtly healthy as determined by a medical evaluation including medical history without clinically relevant pathologies, physical examination, vital signs, ECG assessment, and clinical laboratory result
• eGFR ≥ 90 mL/min and \< 160 mL/min for males or \< 150 mL/min for females
• Body weight within 50.0 and 100.0 kg and BMI within 18.0 and 30.0 kg/m2

You may not qualify if:

• History of any clinically-relevant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrine, haematologic, neuromuscular or allergic disease(s), metabolic disorder, cancer, cirrhosis, significant acute infection, local infection within 2 weeks of dose administration,
• ECG: any history of clinically-significant ECG abnormalities, an uninterpretable ECG, or any of ECG abnormalities, unless considered not significant by the Investigator
• Abnormalities in clinical chemical, haematological, or coagulation variables considered medically relevant by the Investigator,
• Positive urine drug screen, positive breathalyzer for alcohol
• Positive results in any of the following virology tests: HIV-1 and -2 antibodies, HBsAg, and anti-hepatitis C virus antibody
• Positive SARS-CoV-2 antigen test
• Women who are pregnant or nursing,
• Donation or loss of over 500 mL of blood within sixty days prior to the first study drug administration,
• Part C with co-administration of meropenem:
• History of epilepsy (or known seizure disorder), brain lesions or other significant neurological disorders,
• Known history of clinically-significant hypersensitivity or urticaria, or severe allergic reaction to β-lactam antibiotics,
• History of Gilbert syndrome,
• History of any severe antibiotic-associated superinfections,

Sponsors & Collaborators

• Antabio: lead

Study Sites (1)

Biotrial

Rennes, 35042, France

Location

MeSH Terms

Interventions

Meropenem

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sophie Hays, MD

  Biotrial

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: June 15, 2023
• Study Start: April 12, 2023
• Primary Completion: January 5, 2024
• Study Completion: January 5, 2024
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)