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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04903730




Registration number
NCT04903730
Ethics application status
Date submitted
24/05/2021
Date registered
26/05/2021
Date last updated
7/12/2022

Titles & IDs
Public title
Safety, Tolerability, & Pharmacokinetics Study of Single & Multiple Inhaled Doses of Imatinib Inhalation Solution
Scientific 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
Secondary ID [1] 0 0
AER-901-01-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AER-901 Solution for Nebulization
Treatment: Drugs - Placebo

Experimental: AER-901 Solution for Nebulization - 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.

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


Treatment: Drugs: AER-901 Solution for Nebulization
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).

Treatment: Drugs: Placebo
0.45% sterile saline for injection delivered via the FOX MOBILE device.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
From randomization though study completion (up to 17 days following last treatment)
Primary outcome [2] 0 0
Number of Participants with Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From randomization though study completion (up to 17 days following last treatment)
Secondary outcome [1] 0 0
Systemic exposure to imatinib (in plasma) after a single administration of AER-901 (Part A)
Timepoint [1] 0 0
Pre-dose through 72 hours post dose
Secondary outcome [2] 0 0
Systemic exposure to imatinib (in plasma) after multiple administrations of AER-901 (Part B)
Timepoint [2] 0 0
Pre-dose through 96 hours post last dose
Secondary outcome [3] 0 0
Systemic exposure to imatinib (in urine) after single administration of AER-901 (Part A)
Timepoint [3] 0 0
Pre-dose through 72 hours post dose
Secondary outcome [4] 0 0
Systemic exposure to imatinib (in urine) after multiple administrations of AER-901 (Part B)
Timepoint [4] 0 0
Pre-dose through 96 hours post last dose

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/12/2022
Sample size
Target
Accrual to date
Final
83
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Aerami Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04903730
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lisa Yanez
Address 0 0
Chief Operating Officer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04903730