Clinical Trials Register

Summary
EudraCT Number:	2021-006864-25
Sponsor's Protocol Code Number:	AV-101-003
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-11-16
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-006864-25

A.3

Full title of the trial

IMPAHCT-FUL: A Long-Term Extension, Multi-Center Safety Study of AV-101 in Subjects With Pulmonary Arterial Hypertension (PAH) Who Have Completed Study AV-101-002

IMPAHCT-FUL: Studio di estensione a lungo termine, multicentrico, per valutare la sicurezza di AV-101 in soggetti con ipertensione arteriosa polmonare (IAP) che hanno completato lo studio AV-101-002

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 – Follow Up Long Term Extension (IMPAHCT-FUL)

Studio Clinico su Imatinib a Inalazione per l’Ipertensione Arteriosa Polmonare - Follow Up di estensione a Lungo termine (IMPAHCT-FUL)

A.3.2

Name or abbreviated title of the trial where available

IMPAHCT-FUL

A.4.1

Sponsor's protocol code number

AV-101-003

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
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
B.5.3.3	Post code	02451
B.5.3.4	Country	United States
B.5.4	Telephone number	+18883738110
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.3.2	Product code	[NA]
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.3.9.4	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.3.2	Product code	[NA]
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.3.9.4	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.3.2	Product code	[NA]
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.3.9.4	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

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)

Ipertensione Arteriosa Polmonare (IAP)

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.

La IAP comprende rare malattie cardiopolmonari croniche che presentano caratteristiche patologiche comuni di crescita cellulare inappropriata con conseguente aumento della resistenza...

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 the long-term safety and tolerability of AV-101.
The long-term effects of AV-101 on efficacy measures will also be assessed

L’obiettivo primario dello studio è stabilire la sicurezza a lungo termine di AV-101.
Saranno valutati anche gli effetti a lungo termine di AV-101 sulle misure di efficacia.

E.2.2

Secondary objectives of the trial

Not Applicable

NON APPLICABILE

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Key Inclusion Criteria: (Additional criteria, may apply, per the protocol)
To be eligible, a participant is required to be or have:
• Consented to participate in the LTE and has successfully completed the placebo-controlled 24-week Study AV-101-002.
• Female subjects of childbearing potential who have agreed to continue to use a highly effective form of contraception during the LTE and for at least 30 days after completing or discontinuing study treatment (highly effective forms of contraception.

Criteri di inclusione principali:
Per essere idoneo un/a partecipante deve essere o avere:
• Dato il consenso a partecipare allo studio LTE e completato con successo lo studio AV-101-002 controllato con placebo della durata di 24 settimane.
• I soggetti di sesso femminile in età fertile devono avere accettato di continuare a utilizzare una forma di contraccezione altamente efficace durante lo studio LTE e per almeno 30 giorni dopo il completamento o l’interruzione del trattamento dello studio (le forme altamente efficaci di contraccezione sono descritte nella Sezione 7.9).

E.4

Principal exclusion criteria

Key Exclusion Criteria:
Subjects meeting any of the following criteria:
• The Investigator believes that it would not be in the best interest of the subject to be included in the LTE e.g., for clinical or social reasons.
• Subjects who were not compliant with study medication in AV-101-002 as assessed by the Investigator

Criteri di esclusione principali:
Soggetti che soddisfano uno qualsiasi dei seguenti criteri:
• Lo sperimentatore ritiene che non sia nel migliore interesse del soggetto di essere incluso/a nello studio LTE, ad es. per ragioni cliniche o sociali.
• Soggetti che non hanno assunto adeguatamente il farmaco dello studio (compliance) nell’AV-101-002, come valutato dallo sperimentatore.

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability of AV-101.
Other Pre-specified Outcome Measures:
Change from baseline in the 6MWD [Time Frame: Baseline, up to study completion]
Change from baseline in NT-proBNP [Time Frame: Baseline, up to study completion]
Change from baseline in Transthoracic Echo parameters of right ventricular (RV) function [Time Frame: Baseline, up to study completion]
Time to Clinical Worsening [Time Frame: up to study completion]

Sicurezza e tollerabilità di AV-101
Altre misure di esito specificate in precedenza:
variazione dal basale nel Test sulla distanza percorsa in 6 minuti (6MWD) [Time Frame: Baseline, fino al completamento dello studio].
Variazione dal basale nell’NT-proBNP [Time Frame: Baseline, fino al completamento dello studio].
Variazione dal basale nei parametri dell’ecocardiogramma transtoracico della funzione ventricolare destra (RV) [Time Frame: Baseline, fino al completamento dello studio].
Tempo per gli eventi di peggioramento clinico [Time Frame: Baseline, fino al completamento dello studio].

E.5.1.1

Timepoint(s) of evaluation of this end point

Study Completion

Completamento dello Studio

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

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Estensione a lungo termine

Long Term Extension

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

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

Information not present in EudraCT

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

Australia

Brazil

Canada

Chile

China

Colombia

Israel

Mexico

Puerto Rico

Singapore

South Africa

United States

France

Poland

Sweden

Netherlands

Spain

Czechia

Germany

Greece

Italy

Belgium

Ireland

Portugal

Turkey

United Kingdom

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
A subject has completed the study if he/she has completed all study assessments, including the last visit or the last scheduled procedure shown in the Schedule of Assessments.

LVLS
Un soggetto ha completato lo studio se ha completato tutte le valutazioni dello studio, compresa l'ultima visita o l'ultima procedura programmata indicata nel Programma delle valutazioni.

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

E.8.9.2

In all countries concerned by the trial days

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

134

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)

The LTE study will continue until AV-101 is commercially available for study subjects or until the Sponsor stops the study. In the event that the subject has withdrawn/discontinued early from the study, standard of care treatment for the subject’s PAH should be administered by their attending physician.

Lo studio LTE continuerà fino a quando AV-101 sarà disponibile in commercio per i soggetti dello studio o fino a quando lo Sponsor non interromperà lo studio. Nel caso in cui il soggetto si sia ritirato/interrotto anticipatamente dallo studio, il trattamento standard per la IAP del soggetto dovrà essere somministrato dal suo medico curante.

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

2022-11-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-23

P. End of Trial
P.	End of Trial Status	Ongoing

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IMP with orphan designation in the indication
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