IMPAHCT: A Study of AV-101 (Dry Powder Inhaled Imatinib) in Patients With Pulmonary Arterial Hypertension (PAH)

Sponsor

Aerovate Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05036135

Collaborator

(none)

462

Enrollment

Locations

Arms

Anticipated Duration (Months)

28.9

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

IMPAHCT: Inhaled iMatinib Pulmonary Arterial Hypertension Clinical Trial is a Phase 2b/Phase 3 study to evaluate the safety and efficacy of AV-101 (dry powder inhaled imatinib) in patients with Pulmonary Arterial Hypertension (PAH). The Phase 2b part of the study will assess three doses to establish an optimal dose for the Phase 3 part of the study. The Phase 2b primary endpoint will be the placebo corrected change in pulmonary vascular resistance (PVR). The Phase 3 primary endpoint will be the placebo corrected change in 6-minute walk distance (6MWD) after 24 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: AV-101 Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

462 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

IMPAHCT: A Phase 2b/3, Randomized, Double-Blind, Placebo-Controlled, 24-Week Dose Ranging and Confirmatory Study to Evaluate the Safety and Efficacy of AV-101 in Patients With Pulmonary Arterial Hypertension (PAH)

Actual Study Start Date :

Dec 2, 2021

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2b low dose AV-101	Drug: AV-101 AV-101 (imatinib) administered via dry powder inhalation
Experimental: Phase 2b medium dose AV-101	Drug: AV-101 AV-101 (imatinib) administered via dry powder inhalation
Experimental: Phase 2b high dose AV-101	Drug: AV-101 AV-101 (imatinib) administered via dry powder inhalation
Placebo Comparator: Phase 2b Placebo	Drug: Placebo Placebo administered via dry powder inhalation
Experimental: Phase 3 dose AV-101 (Optimal dose selected in Phase 2b)	Drug: AV-101 AV-101 (imatinib) administered via dry powder inhalation
Placebo Comparator: Phase 3 Placebo	Drug: Placebo Placebo administered via dry powder inhalation

Outcome Measures

Primary Outcome Measures

Phase 2b: Change from Baseline in Pulmonary Vascular Resistance (PVR) [24 weeks]
Phase 3: Change from Baseline in Six Minute Walk Distance (6MWD) [24 weeks]

Secondary Outcome Measures

Phase 2b: Change from Baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) [24 weeks]
Phase 2b: Change from Baseline in Six Minute Walk Distance (6MWD) [24 weeks]
Phase 2b: Incidence of Clinical Worsening [24 weeks]
Phase 2b: Proportion of Subjects with Improvement in WHO Functional Class [24 weeks]
Phase 2b: Change from Baseline in Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Risk Score [24 weeks]
REVEAL Lite 2.0 risk scores range from 1 to 14; a higher score represents higher risk
Phase 2b: Change from Baseline in Health-Related Quality of Life emPHasis-10 Questionnaire Score [24 weeks]
emPHasis-10 questionnaire scores range from 0 - 50; a higher score represents a higher symptom burden
Phase 3: Change from Baseline in NT-proBNP [24 weeks]
Phase 3: Time to Clinical Worsening [24 weeks]
Phase 3: Proportion of Subjects with Improvement in WHO Functional Class [24 weeks]
Phase 3: Change from Baseline in Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Risk Score [24 weeks]
REVEAL Lite 2.0 risk scores range from 1 to 14; a higher score represents higher risk
Phase 3: Change from Baseline in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire Score [24 weeks]
PAH-SYMPACT is a patient reported outcome instrument developed to assess PAH symptoms and impacts

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria

PAH belonging to one of the subgroups:

I/HPAH, PAH-CTD,
PAH due to drugs and/or toxins/chemicals (having been in the care of the investigator for at least one year with no relapses of drug or toxin/chemical abuse),
HIV associated or
PAH due to repaired congenital heart disease (at least 1 year since repair)

World Health Organization (WHO) Functional Class II, III or IV symptoms
Stable concomitant background therapy of at least two PAH approved medications
Able to walk a distance of at least 100 m but no more than 475 m during the Screening 6-minute walk tests.

Key Exclusion Criteria

Pulmonary hypertension (PH) belonging to Groups 2 to 5
A history of left-sided heart disease
Pregnant or breast-feeding females

Additional criteria may apply, per protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona	United States	85012
2	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
3	Dept of Veterans Affairs Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
4	Georgetown University Hospital	Washington	District of Columbia	United States	20007
5	George Washington University Medical Faculty Associates, Inc.	Washington	District of Columbia	United States	20073
6	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
7	Indiana University Health	Indianapolis	Indiana	United States	46202
8	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
9	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
10	New York-Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York	United States	11215
11	Duke University Medical Center - Duke South Clinic	Durham	North Carolina	United States	27710
12	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
13	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
14	Sunshine Coast University Hospital	Birtinya	Queensland	Australia	4575
15	Hopital Erasme - Cliniques Universitaires de Bruxelles	Brussels		Belgium	1070
16	Hospital 12 de Octubre	Madrid		Spain	28014