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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: AV-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | REVEAL Lite 2.0 risk scores range from 1 to 14; a higher score represents higher risk | 24 weeks | 
| Phase 2b: Change from Baseline in Health-Related Quality of Life emPHasis-10 Questionnaire Score | emPHasis-10 questionnaire scores range from 0 - 50; a higher score represents a higher symptom burden | 24 weeks | 
| 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 | REVEAL Lite 2.0 risk scores range from 1 to 14; a higher score represents higher risk | 24 weeks | 
| Phase 3: Change from Baseline in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire Score | PAH-SYMPACT is a patient reported outcome instrument developed to assess PAH symptoms and impacts | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAH, Pulmonary Arterial Hypertension, Lungs, Pulmonary, AV-101, imatinib, IMPAHCT