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

• ClinicalTrials.gov Identifier: NCT04903730
• Recruitment Status: Recruiting
• First Posted: May 26, 2021
• Last Update Posted: February 16, 2022
• Sponsor: Aerami Therapeutics
• Information provided by (Responsible Party): Aerami Therapeutics

Tracking Information

• First Submitted Date: May 24, 2021
• First Posted Date: May 26, 2021
• Last Update Posted Date: February 16, 2022
• Actual Study Start Date: May 24, 2021
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 24, 2021)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From randomization though study completion (up to 17 days following last treatment) ]
  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)
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: From randomization though study completion (up to 17 days following last treatment) ]
  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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 24, 2021)

• Systemic exposure to imatinib (in plasma) after a single administration of AER-901 (Part A) [ Time Frame: Pre-dose through 72 hours post dose ]
  Plasma will be collected pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 9 h, 12 h , 24 h, 48 h, and 72 h post dose.
• Systemic exposure to imatinib (in plasma) after multiple administrations of AER-901 (Part B) [ Time Frame: Pre-dose through 96 hours post last dose ]
  Plasma will be collected at Days 1, 3, 5, and 7 at pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 9 h, 12 h (and 24 h, 48 h, 72 h, and 96 h post last dose).
• Systemic exposure to imatinib (in urine) after single administration of AER-901 (Part A) [ Time Frame: Pre-dose through 72 hours post dose ]
  Urine will be collected pre-dose, and post dose on Day 1, 24 h, 48 h, 72 h post dose
• Systemic exposure to imatinib (in urine) after multiple administrations of AER-901 (Part B) [ Time Frame: Pre-dose through 96 hours post last dose ]
  Urine will be collected pre-dose, and post dose on Days 1, 3, 5, 7 and 24 h, 48 h, 72 h, and 96 h post last dose

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, & Pharmacokinetics Study of Single & Multiple Inhaled Doses of Imatinib Inhalation Solution
• Official Title: A Randomised, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Inhaled Doses of Imatinib Inhalation Solution (AER-901) in Adult Healthy Volunteers

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 2 parts and an optional third part:

• Part A: double-blind, placebo-controlled, single ascending dose (SAD).
• Part B: double-blind, placebo-controlled, multiple-ascending dose (MAD).
• Part C (optional): an open-label, single-dose, 2-way crossover. Each part of the study will include a 28-day screening period, a treatment period, and follow-up period.

Detailed Description

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 2 parts and an optional third part:

• Part A: double-blind, placebo-controlled, single ascending dose (SAD).
• Part B: double-blind, placebo-controlled, multiple-ascending dose (MAD).
• Part C (optional): an open-label, single-dose, 2-way crossover.

The decision to proceed with Part C will be made by the Sponsor after reviewing unblinded safety and PK data from Part A and Part B of the study.

Oversight for the study will be provided by a safety review committee (SRC). The decision to progress from Cohort A1 to Cohort A2 will be based on safety and tolerability data from Cohort A1. The decision to progress from Cohort A2 to Cohort A3 will be based on review of safety and tolerability data from Cohort A2 and PK data from Cohort A1 by the SRC. A similar sequence will follow for subsequent progression decisions by the SRC for all the cohorts in Part A and Part B of the study.

Each part of the study will include a 28-day screening period, a treatment period, and follow-up period.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

In Part A of the study, participants will be enrolled into 1 of up to 5 sequential cohorts (Cohorts A1 to A5). Each cohort will consist of 8 participants (6 participants receiving AER 901 and 2 participants receiving placebo).

In Part B, participants will be enrolled into 1 of up to 4 cohorts (Cohorts B1 to B4). Each cohort will consist of 8 participants (6 participants receiving AER 901 and 2 participants receiving placebo).

Part C of the study (optional), which has a 2-way crossover design, will compare a single treatment of oral imatinib (Gleevec®) versus a single treatment of inhaled AER 901 (dose TBD). Participants will be enrolled into a single cohort (Cohort C1).

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

All parts of the study will be double masked. The Sponsor, Investigator, 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.

Primary Purpose: Basic Science

• Condition: Pulmonary Arterial Hypertension

Intervention

• Drug: AER-901 Solution for Nebulization

  Part A: participants will be enrolled into 1 of up to 5 sequential cohorts (Cohorts A1 to A5). Inhaled AER-901 doses of 5 mg, 10 mg, 20 mg, 40 mg, and 80 mg are planned. Each cohort will consist of 8 participants (6 participants receiving inhaled AER-901 and 2 participants receiving inhaled placebo).

  Part B: participants will be enrolled into 1 of up to 4 cohorts (Cohorts B1 to B4).

  Each cohort will consist of 8 participants (6 participants receiving AER 901 and 2 participants receiving placebo).

  Other Name: AER-901
• Drug: Placebo
  0.45% sterile saline for injection delivered via the FOX MOBILE device.
  Other Name: Placebo for Nebulization

Study Arms

• Experimental: AER-901 Solution for Nebulization
  AER-901 is supplied in two solution strengths (5 mg/mL and 40 mg/mL) for nebulization delivered via the FOX® MOBILE device.
  Intervention: Drug: AER-901 Solution for Nebulization
• Placebo Comparator: Placebo
  A volume-matching placebo (0.45% sterile saline for injection) is to be delivered via the FOX® MOBILE device.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 24, 2021): 78
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Provide written consent.
2. Body weight ≥ 50 kg, and a body mass index 18.0 to 32.0, inclusive.
3. Female participants of non child bearing potential or if of child bearing potential, agrees to take effective contraceptive measures throughout the study period.
4. 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.
5. Forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) ratio of at least 0.7.
6. Values for FEV1 and FVC of at least 80% of the predicted value.
7. 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.
8. Able to successfully perform spirometry and use the inhalation device at Screening.
9. Negative result for cotinine in the urine drug screen, at Screening and on Day -1.

Exclusion Criteria:

1. 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.
2. Pregnant or lactating or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
3. Presence of acute or chronic illness or history of chronic illness.
4. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary artery disease, or history of any psychotic mental illness.
5. Upper or lower respiratory tract infection within 4 weeks before the first dose of treatment.
6. 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.
7. Any clinically significant arrhythmia(s) at Screening ECG.
8. 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.
9. 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).
10. 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).
11. Suffering from post-COVID-19 syndrome or have tested positive for COVID-19 infection within 3 months prior to the first dose of treatment.
12. Participation in another clinical study of a new chemical entity, new device, or a prescription medicine within 3 months before dosing.
13. 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.
14. 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.
15. Current or previous use of tobacco, nicotine products, vaping device or e-cigarettes within the past 6 months.
16. Loss of more than 400 mL blood (e.g., as a blood donor, or donor of blood products), during the 3 months before screening.
17. Received any vaccination (e.g. for COVID-19 or influenza) within 6 weeks of treatment or plans to receive a vaccination during the study.
18. History of Mycobacterium tuberculosis infection, or latent M. tuberculosis infection.
19. Active or latent parasitic infection, have travelled to or have an intention to travel to a country with a high prevalence of parasitic infections within 3 months before or after receiving the treatment.
20. Evidence of any other clinically significant infection, including bacterial or viral infections, at Screening and Day -1.
21. Presence of any underlying physical and/or psychological medical condition that would make it unlikely that the participant will comply with the protocol or complete the study per protocol.
22. An employee of the study site or Sponsor who is directly involved in the study, or a family member of such a person.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Michelle Widmann; see email; mwidmann@calclinicalsolutions.com

Contact: Lisa Chung; see email; lisa.chung@novotech-cro.com

• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04903730
• Other Study ID Numbers: AER-901-01-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Aerami Therapeutics
• Study Sponsor: Aerami Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Timm Crowder, PhD; President

• PRS Account: Aerami Therapeutics
• Verification Date: February 2022