Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT) or A Phase 2b/3, Randomized, Controlled, 24-week Dose Ranging and Confirmatory Study of AV-101 in Patients with PAH

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aerovate Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

30 Jun 2022 → 9 Aug 2024

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Aerovate Therapeutics Inc

External identifiers

EU CT number

2023-508734-34-00

EudraCT number

2021-001910-13

ClinicalTrials.gov

NCT05036135

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety, Pharmacokinetic

The objective of the study is to establish an optimal dose based primarily upon the change in PVR assessed by right heart catheterization (RHC) and the safety and tolerability of AV-101 as evaluated in the Phase 2b Part of the study. The optimal dose will be taken into the Phase 3 Part of the study where the placebo-corrected change in 6MWD after 24 weeks of treatment will be used as the primary endpoint.

Conditions and MedDRA coding

Pulmonary Arterial Hypertension (PAH)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male or female between 18 and 75 years of age inclusive at the Screening Visit
2. A diagnosis of PAH belonging to one of the subgroups of the NICE classification of Group 1*: a. I/HPAH, PAH-CTD, b. 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), c. HIV associated or d. PAH due to repaired congenital heart disease (at least 1 year since repair). *Excluding patients with Portopulmonary Hypertension
3. World Health Organization (WHO) Functional Class II, III or IV symptoms
4. Must be able to walk a distance of at least 100 m but no more than 475 m during the screening 6-minute walk test.

Exclusion criteria 3

1. Pulmonary hypertension (PH) belonging to Groups 2 to 5 of the 2018 NICE classification and Group 1 diagnosed with Portopulmonary Hypertension.
2. A history of left ventricular ejection fraction (LVEF) ≤ 40% on echocardiogram within 12 months of screening, or clinically significant ischemic, mitral or aortic valve disease, or constrictive heart disease, in the opinion of the Investigator
3. Pregnant or breast-feeding females

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Endpoint (Phase 2b): Placebo corrected change from baseline at Week 24 in PVR
2. Primary Endpoint (Phase 3): Placebo corrected change from baseline at Week 24 in the 6MWD

Secondary endpoints 11

1. Secondary Endpoint (Phase 2b): Change from baseline at Week 24 in NT-proBNP
2. Secondary Endpoint (Phase 2b): Change from baseline at Week 24 in 6MWD
3. Secondary Endpoint (Phase 2b): Incidence of Clinical Worsening events
4. Secondary Endpoint (Phase 2b): Improvement at Week 24 in WHO Functional Class
5. Secondary Endpoint (Phase 2b): Change in REVEAL Lite 2.0 risk score
6. Secondary Endpoint (Phase 2b): Change from baseline at Week 24 in QoL
7. Secondary Endpoint (Phase 3): Change from baseline at Week 24 in NT-proBNP
8. Secondary Endpoint (Phase 3): Time to Clinical Worsening events
9. Secondary Endpoint (Phase 3): Improvement at Week 24 in WHO Functional Class
10. Secondary Endpoint (Phase 3): Change in REVEAL Lite 2.0 risk score
11. Secondary Endpoint (Phase 3): Change from baseline at Week 24 in QoL

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aerovate Therapeutics Inc.

Sponsor organisation

Aerovate Therapeutics Inc.

Address

200 Berkeley Street Fl 18

City

Boston

Postcode

02116-5035

Country

United States

Scientific contact point

Organisation

Aerovate Therapeutics Inc.

Contact name

Medical Monitor

Public contact point

Organisation

Aerovate Therapeutics Inc.

Contact name

Medical Monitor

Third parties 2

Locations

14 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications