Safety, Tolerability, & Pharmacokinetics Study of Single & Multiple Inhaled Doses of Imatinib Inhalation Solution

NCT04903730 | Completed Phase 1 DMC

• 1 other identifier: AER-901-01-001
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and PK of single and multiple inhaled doses of imatinib inhalation solution (AER-901) in healthy adult volunteers. This study consists of 3 parts and an optional fourth part.

Conditions

Pulmonary Arterial Hypertension

Keywords

Healthy Subjects; Imatinib; AER-901; PAH; Imatinib mesylate; inhalation; inhaled; nebulization; FOX Mobile; inhaler; Gleevec

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  TEAEs will be summarized by treatment group using frequency and percent for each system organ class and preferred term within each system, organ and class (SOC)

  From randomization though study completion (up to 17 days following last treatment)

• Number of Participants with Serious Adverse Events (SAEs)

  SAEs will be summarized by treatment group using frequency and percent for each system organ class and preferred term within each system, organ and class (SOC)

  From randomization though study completion (up to 17 days following last treatment)

Secondary Outcomes (4)

• Systemic exposure to imatinib (in plasma) after a single administration of AER-901 (Part A)

  Pre-dose through 72 hours post dose

• Systemic exposure to imatinib (in plasma) after multiple administrations of AER-901 (Part B)

  Pre-dose through 96 hours post last dose

• Systemic exposure to imatinib (in urine) after single administration of AER-901 (Part A)

  Pre-dose through 72 hours post dose

• Systemic exposure to imatinib (in urine) after multiple administrations of AER-901 (Part B)

  Pre-dose through 96 hours post last dose

Study Arms (2)

AER-901 Solution for Nebulization

EXPERIMENTAL

The inhalation formulation AER-901 for Part A and Part B (Cohort B1 only) is a sterile, yellow solution composed of imatinib mesylate and sterile water for injection. AER-901 will be supplied in 2 solution strengths (5 mg/mL and 40 mg/mL) for nebulisation. The AER-901 inhalation formulation for Part D is a sterile yellow solution composed of imatinib mesylate, sterile water for injection and propylene glycol. AER-901 will be supplied in 2 solution strengths (5 mg/mL and 40 mg/mL) and the Pharmacy Manual will provide guidance on preparation for nebulization. Following review of the Part D safety and PK data by the SRC, the SRC will recommend which formulation and dose of AER-901 (sterile water vs propylene glycol) will be used in Parts B (Cohorts B2 and B3) and Part C. The solution will be filled into a suitable container-closure system and delivered via a nebuliser known as the FOX® MOBILE. The water acts as the medium for nebulisation.

Drug: AER-901 Solution for Nebulization

Placebo

PLACEBO COMPARATOR

A volume-matching placebo (0.45% sterile saline for injection) is to be delivered via the FOX® MOBILE device.

Drug: Placebo

Interventions

AER-901 Solution for Nebulization DRUG

Part A: participants will be enrolled into 1 of up to 5 sequential cohorts (A1 to A5). Inhaled AER-901 doses of 5, 10, 20, 40, and 80mg are planned. Part B: participants will be enrolled into 1 of up to 3 cohorts (B1 to B3). Cohorts B2 and B3 will commence following Part D of the study and following SRC review of safety, tolerability, and PK data. A decision to dose with either a propylene glycol formulation or a sterile water formulation will be made by the SRC at the time of the review of the Part D data. Part D has a three-part design (Treatment Periods 1 \& 2 separated by a Washout period) and will compare placebo to a single-dose of AER-901 (5 mg/mL QD) followed by two doses of AER-901. Each cohort will consist of 8 participants (6 receiving AER 901 and 2 receiving placebo).

Also known as: AER-901

AER-901 Solution for Nebulization

Placebo DRUG

0.45% sterile saline for injection delivered via the FOX MOBILE device.

Also known as: Placebo for Nebulization

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written consent.
• Body weight ≥ 50 kg, and a body mass index 18.0 to 32.0, inclusive.
• Female participants of non child bearing potential or if of child bearing potential, agrees to take effective contraceptive measures throughout the study period.
• Male participant: has undergone bilateral vasectomy or agrees to use effective contraceptive effective contraceptive measures or abstinence, and not donate sperm throughout the study until at least 3 months after the last dose of IP.
• Forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) ratio of at least 0.7.
• Values for FEV1 and FVC of at least 80% of the predicted value.
• Able to understand the nature of the study and any hazards of participation, and ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire study.
• Able to successfully perform spirometry and use the inhalation device at Screening.
• Negative result for cotinine in the urine drug screen, at Screening and on Day -1.

You may not qualify if:

• Clinically significant physical findings, vital signs, ECG, or laboratory values that could interfere with the objectives of the study or the safety of the subject.
• Pregnant or lactating or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
• Presence of acute or chronic illness or history of chronic illness.
• Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary artery disease, or history of any psychotic mental illness.
• Upper or lower respiratory tract infection within 4 weeks before the first dose of treatment.
• Any medically identified respiratory disease(s) and/or condition(s), including but not limited to current asthma, chronic obstructive pulmonary disease, and diagnosed obstructive sleep apnoea syndrome.
• Any clinically significant arrhythmia(s) at Screening ECG.
• History of surgery or medical intervention, or planned surgery or medical intervention, that could interfere with the objectives of the study or the safety of the volunteer.
• Currently taking any drug including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days before the first dose and throughout the study, with the exception of acetylsalicylic acid (aspirin).
• Positive test result(s) for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HbsAg), human immunodeficiency virus (HIV) antibody, or coronavirus disease of 2019 (COVID-19).
• Suffering from post-COVID-19 syndrome or have tested positive for COVID-19 infection within 3 months prior to the first dose of treatment.
• Participation in another clinical study of a new chemical entity, new device, or a prescription medicine within 3 months before dosing.
• Regular alcohol consumption at levels which may increase risk of harm from alcohol-related disease or injury. Participant is unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU and for the duration of the study.
• A history of substance abuse or dependency in the last 12 months, or a history of recreational intravenous drug use over the last 5 years, or a positive toxicology screening panel (urine test including qualitative identification of barbiturates, THC, amphetamines, methamphetamines, MDMA, phencyclidine, benzodiazepines, opiates and cocaine), or alcohol breath test.
• Current or previous use of tobacco, nicotine products, vaping device or e-cigarettes within the past 6 months.

Sponsors & Collaborators

• Aerami Therapeutics: lead

Study Sites (1)

CMAX

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lisa Yanez

  Chief Operating Officer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Only Parts A, B and BD of the study will be double blinded. The Sponsor, PI and their designee/s, MM, study personnel, and participants are not to make any effort to determine which IP therapy is being received. Unmasked pharmacy personnel will be used in this study to prepare the IP.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomised, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and PK of single and multiple inhaled doses of imatinib inhalation solution (AER-901) in healthy adult volunteers. This study consists of 3 parts and an optional fourth part: * Part A: double-blind, placebo-controlled, single ascending dose (SAD). * Part B: double-blind, placebo-controlled, multiple ascending dose (MAD). * Part C (optional): open-label, single-dose, crossover. The decision to proceed with Part C will be made by the Sponsor after reviewing unblinded safety and PK data from Part D of the study. * Part D: double-blind, placebo-controlled, 5 mg single dose (SD) followed by a twice daily (BID) 5 mg dose (total daily dose of 10 mg) of AER-901 in a propylene glycol formulation vs. placebo.

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: May 26, 2021
• Study Start: May 24, 2021
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: December 7, 2022

Record last verified: 2022-12

Locations

AU (1)