Clinical Trials Register

Summary
EudraCT Number:	2021-001910-13
Sponsor's Protocol Code Number:	AV-101-002
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-11-18
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2021-001910-13

A.3

Full title of the trial

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).

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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.

A.3.2

Name or abbreviated title of the trial where available

IMPAHCT

A.4.1

Sponsor's protocol code number

AV-101-002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05036135

A.5.4

Other Identifiers

Name:

US IND

Number:

145658

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Aerovate Therapeutics, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Aerovate Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aerovate Therapeutics, Inc.
B.5.2	Functional name of contact point	Medical Monitor
B.5.3	Address:
B.5.3.1	Street Address	930 Winter Street, Suite M-500
B.5.3.2	Town/ city	Waltham, MA
B.5.3.3	Post code	02451
B.5.3.4	Country	United States
B.5.4	Telephone number	+1888373-8110
B.5.6	E-mail	clinicaltrials@aerovatetx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/21/2449
D.3 Description of the IMP
D.3.1	Product name	AV-101
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IMATINIB
D.3.9.1	CAS number	152459-95-5
D.3.9.2	Current sponsor code	AV-101
D.3.9.3	Other descriptive name	Not Available
D.3.9.4	EV Substance Code	SUB25387
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/21/2449
D.3 Description of the IMP
D.3.1	Product name	AV-101
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IMATINIB
D.3.9.1	CAS number	152459-95-5
D.3.9.2	Current sponsor code	AV-101
D.3.9.3	Other descriptive name	Not Available
D.3.9.4	EV Substance Code	SUB25387
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	17.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/21/2449
D.3 Description of the IMP
D.3.1	Product name	AV-101
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IMATINIB
D.3.9.1	CAS number	152459-95-5
D.3.9.2	Current sponsor code	AV-101
D.3.9.3	Other descriptive name	Not Available
D.3.9.4	EV Substance Code	SUB25387
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	35
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pulmonary Arterial Hypertension (PAH)

E.1.1.1

Medical condition in easily understood language

PAH includes rare, chronic cardiopulmonary diseases involving common pathologic features of inappropriate cell growth resulting in increased resistance to blood flow through the pulmonary vasculature.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10064911
E.1.2	Term	Pulmonary arterial hypertension
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10077729
E.1.2	Term	Pulmonary arterial hypertension WHO functional class III
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10077730
E.1.2	Term	Pulmonary arterial hypertension WHO functional class IV
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10077740
E.1.2	Term	Pulmonary arterial hypertension WHO functional class II
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of the study is to establish an optimal dose of AV-101 based primarily upon the change in PVR (assessed by right heart catherization) 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.

E.2.2

Secondary objectives of the trial

Change from baseline in NT-proBNP levels, Time to Clinical Worsening's, Multicomponent Clinical Improvements, Maintenance or Improvement of Functional Class, Change in REVEAL Lite 2.0 score and Quality of Life will be evaluated.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

The sub-study is the Pharmacokinetic study conducted in Phase 2b part of the study.

At selected study sites in the Phase 2b Part of the study, steady state pharmacokinetics will be assessed at Week 4 pre-dose and at multiple timepoints post-administration of the study medication.
A pre-dose trough PK sample will be taken from all subjects in the study at the Week 24 visit prior to any other procedures (excluding HRQoL and vital signs). The purpose of the Week 24 PK sample is to allow for potential exposure-response analyses for efficacy and safety.

E.3

Principal inclusion criteria

Key Inclusion Criteria:

1. Male or female adults (between 18 and 75 years) at the Screening
Visit within 28 days prior to Day 1
2. Subjects with a diagnosis of PAH belong to one of the subgroups of the NICE classification of Group 1:
- a. I/HPAH, PAH-CTD
- b. PAH due to drugs and toxins (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.

E.4

Principal exclusion criteria

Key Exclusion Criteria:

1. PH belonging to Groups 2 to 5 of the 2018 NICE classification and Group 1 diagnosed with Portopulmonary Hypertension.
2. A history of 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

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint (Phase 2b)
● The placebo-corrected change from baseline in PVR at 24 weeks

Primary Endpoint (Phase 3)
● The placebo-corrected change in 6MWD at Week-24

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

E.5.2

Secondary end point(s)

Key Secondary Endpoints for Phase 2B:
● Change from baseline at Week 24 in NT-proBNP
● Change from baseline at Week 24 in 6MWD
● Incidence of Clinical Worsening through 24 Weeks
● Improvement at Week 24 in WHO Function Class status
● Change from baseline at Week 24 in REVEAL Lite 2.0 Score
● Change from baseline at Week 24 in QoL (emPHasis-10) Questionnaire score

Key Secondary Endpoints for Phase 3:
● Change from baseline at Week 24 in NT-proBNP
● Time to Clinical Worsening through 24 weeks
● Improvement at Week 24 in WHO Function Class status
● Change from baseline at Week 24 in REVEAL Lite 2.0 Score
● Change from baseline at Week 24 in QoL (PAH-SYMPACT) Questionnaire score

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase 2b and Phase 3 endpoints will be evaluated at Week 24 except for safety and PK. Safety will be evaluated throughout the study and PK will be evaluated at Week 4 and Week 24.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Chile

Colombia

Singapore

Puerto Rico

Australia

Brazil

Canada

China

Israel

Mexico

South Africa

Turkey

United Kingdom

United States

Austria

Belgium

Czechia

France

Germany

Greece

Ireland

Italy

Latvia

Netherlands

Poland

Portugal

Spain

Sweden

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS
The end of Phase 2b is defined as the Week 24 visit for the last subject(s) who participates in the Phase 2b Part of the study. The end of the Phase 3 Part of the study is defined as the date of last contact with the last subject who participates in the Phase 3 Part of the study (i.e., last subject’s last visit), including subjects in the Intermediate Part

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

323

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

139

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

144

F.4.2.2

In the whole clinical trial

462

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All subjects in the study will be able to enroll in a Long Term Extension (Study AV-101-003) upon completion of the 24-week placebo-controlled Phase 2b or Phase 3 parts of the study.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-01-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-07-05

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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