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    Summary
    EudraCT Number:2021-001910-13
    Sponsor's Protocol Code Number:AV-101-002
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-12-23
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2021-001910-13
    A.3Full 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.3.1Title 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.3.2Name or abbreviated title of the trial where available
    IMPAHCT
    A.4.1Sponsor's protocol code numberAV-101-002
    A.5.4Other Identifiers
    Name:US INDNumber:145658
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAerovate Therapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAerovate Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAerovate Therapeutics, Inc.
    B.5.2Functional name of contact pointHunter Gillies
    B.5.3 Address:
    B.5.3.1Street Address200 Berkeley Street, Fl 18
    B.5.3.2Town/ cityBoston, MA
    B.5.3.3Post code02116
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1(650)703-7269
    B.5.6E-mailhgillies@aerovatetx.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/21/2449
    D.3 Description of the IMP
    D.3.1Product nameAV-101
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIMATINIB
    D.3.9.1CAS number 152459-95-5
    D.3.9.2Current sponsor codeAV-101
    D.3.9.3Other descriptive nameNot Available
    D.3.9.4EV Substance CodeSUB25387
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/21/2449
    D.3 Description of the IMP
    D.3.1Product nameAV-101
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIMATINIB
    D.3.9.1CAS number 152459-95-5
    D.3.9.2Current sponsor codeAV-101
    D.3.9.3Other descriptive nameNot Available
    D.3.9.4EV Substance CodeSUB25387
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number17.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/21/2449
    D.3 Description of the IMP
    D.3.1Product nameAV-101
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIMATINIB
    D.3.9.1CAS number 152459-95-5
    D.3.9.2Current sponsor codeAV-101
    D.3.9.3Other descriptive nameNot Available
    D.3.9.4EV Substance CodeSUB25387
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number35
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary Arterial Hypertension (PAH)
    E.1.1.1Medical 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.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10064911
    E.1.2Term Pulmonary arterial hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10077729
    E.1.2Term Pulmonary arterial hypertension WHO functional class III
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10077730
    E.1.2Term Pulmonary arterial hypertension WHO functional class IV
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10077740
    E.1.2Term Pulmonary arterial hypertension WHO functional class II
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main 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.2.2Secondary 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.2.3Trial contains a sub-study Yes
    E.2.3.1Full 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.3Principal inclusion criteria
    For inclusion in the study, all of the following inclusion criteria must be fulfilled:
    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)
    3. World Health Organization (WHO) Functional Class II, III or IV symptoms
    4. Meets all of the following hemodynamic criteria by means of an RHC at Screening: mPAP ≥ 25 mmHg, PVR > 400 dynes.sec/cm5 and PCWP ≤ 15 mmHg. For the Intermediate and Phase 3 Parts, RHC procedures performed within 6-months of screening may be accepted provided the RHC was conducted as described in the Protocol
    5. On a stable background of at least two PAH medications. Parenteral and oral prostacyclins (including prostanoids and prostacyclin receptor antagonists) are permitted. Subjects should have been stable on their PAH medications for at least 90 days. Stability of parenteral prostacyclins means a change of no more than 10% in the previous 12 weeks
    6. A history of ventilation/perfusion (V/Q) scan, pulmonary arteriogram, or CT angiogram negative for chronic thromboembolic pulmonary hypertension (CTEPH) at the time of their Group 1 PAH diagnosis
    7. Must meet all of the following criteria for pulmonary function (spirometry) tests completed no more than 24 weeks before the Screening Visit: FEV1 ≥ 60% of predicted normal and FEV1:FVC ratio ≥ 0.60
    8. Must have a resting arterial oxygen saturation (SaO2) ≥ 90%, with or without supplemental oxygen, as measured by pulse oximetry at the Screening Visit
    9. 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. In addition, the subject must be able to demonstrate a stable baseline for the 6 minute walk tests between the Screening and Randomization Visits as described in the Protocol
    10. Able to understand the study procedures and be willing to comply with the study restrictions Willing and able to sign a written informed consent prior to all study-related procedures
    11. Female subjects of childbearing potential must agree to use an acceptable form of contraception for at least 28 days prior to when they will receive the first dose of study drug, and for at least 30 days after completing or discontinuing study treatment
    12. Evidence of negative test for SARS-CoV-2, by PCR, at the Screening Visit; Subjects with a previous COVID-19 infection may be included provided the PCR test is negative for SARS-CoV-2 and they do not have chronic symptoms as a result of COVID-19. COVID-19 testing may be performed at local lab, per site/local guidelines, or via the study Central Lab. Subjects who have been fully vaccinated against SARS-CoV-2 may be enrolled without need for PCR testing
    13. Has not enrolled in an exercise training program for pulmonary rehabilitation within 12 weeks prior to the Screening Visit and must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of the study
    14. If currently enrolled in an exercise training program for pulmonary rehabilitation for more than 12 weeks at the time of the Screening Visit, must agree to maintain their current level of rehabilitation for the first 24 weeks of the study
    E.4Principal exclusion criteria
    1. Taking warfarin (or any vitamin K antagonists), Direct Oral Anticoagulants (DOACs) or dual antiplatelet therapy within 2 weeks prior to Day 1/Randomization. (DSMB and Sponsor will decide whether to allow warfarin in Phase 3 Part of the study)
    2. PH belonging to Groups 2 to 5 of the 2018 NICE classification
    3. A history of LVEF ≤ 40% on echocardiogram within 6 months of screening, or clinically significant ischemic, mitral or aortic valve disease, or constrictive heart disease in the opinion of the Investigator
    4. Evidence of ≥ 3 of the following left ventricular disease/dysfunction risk factors:
    - a) Body mass index (BMI) ≥ 30 at the Screening Visit or
    - b) History of essential hypertension
    - c) Diabetes mellitus – any type
    - d) Historical evidence of significant coronary artery disease (CAD) established by any one of the following:
    - i. History of myocardial infarction
    - ii. History of Percutaneous Coronary Intervention (PCI)
    - iii. Angiographic evidence of Coronary Artery Disease (CAD) (> 50% stenosis in at least on vessel), by angiography
    - iv. Positive stress test with imaging
    - v. Previous coronary artery surgery
    - vi. History of chronic stable angina or unstable angina
    5. Taking inhaled prostacyclins within the past 3 months prior to the Screening Visit
    6. History of chronic uncontrolled asthma (subjects taking corticosteroids will be allowed into the study)
    7. History of any illness or condition that, in the opinion of the Investigator could confound the results of the study or pose an additional risk to the subject through their participation in the study
    8. Inability to use or may have potential difficulties using an inhaler device during each dosing period
    9. Participating in a clinical study (e.g., attending follow-up visits) or who have received an investigational drug (new chemical entity) in the past 30 days prior to the Screening Visit. Involvement in strictly observational studies (Registries) is allowed provided this is approved by the Contract Research Organization (CRO) Medical Monitor
    10. Donated blood, plasma, or platelets in the month prior to screening or who have made donations on more than two occasions within the 12 months preceding the first dose administration of study drug or have had a loss of ≥ 400 mL of blood within 2 months prior to Day 1/Randomization
    11. Deficient thrombocyte function, thrombocytopenia < 50 x10^9/L (50 x 10^3/μL) at the Screening Visit
    12. Uncontrolled systemic arterial hypertension, systolic > 180 mm Hg or diastolic >110 mm Hg at the Screening Visit or Day 1/Randomization Visit
    13. QTcF > 450 msec for males and > 470 msec for females at the Screening Visit in the absence of right bundle branch block
    14. History of Long QT Syndrome or Torsade de Pointes
    15. Hemoglobin < 80 g/L (8 g/dL) at the Screening Visit
    16. Serum ALT or AST lab value that is > 3 x ULN at the Screening Visit
    17. Severe renal impairment (eGFR <30 mL/min/1.73m2 at the Screening Visit based on the CKD-EPI equation)
    18. Severe hepatic impairment (Child-Pugh Class C with or without cirrhosis) at the Screening Visit
    19. Known deficiencies of blood coagulation, inherited, or acquired blood coagulation disorders, factor XII, factor XIII; decreased generation of coagulation factors due to acute or chronic liver diseases, inefficient coagulation e.g., due to autoantibodies against coagulation factors such as in lupus anticoagulant, DIC etc
    20. Evidence or history of major bleeding or intracranial hemorrhage
    21. History of elevated intracranial pressure
    22. Significant history or drug allergy as determined by the Investigator
    23. Known or suspected drug hypersensitivity to any component of the trial drug (lactose intolerant subjects are allowed into the study)
    24. Clinically relevant history or current psychological abnormality (including alcohol abuse), psychiatric or neurological illness or autonomic neuropathy, which in the opinion of the Investigator could jeopardize or would compromise the subject’s ability to participate in the trial
    25. Recent major surgical intervention which in the opinion of the Investigator would compromise the subject’s ability to participate in the trial
    26. Pregnant or breast-feeding females
    27. Receiving the SARS-CoV-2 vaccination from 1 week prior to the Screening Visit and through 4 weeks post-Day1/Randomization
    28. Post COVID-19 chronic symptoms (“Long Haulers”) at Screening
    E.5 End points
    E.5.1Primary 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.5.1.1Timepoint(s) of evaluation of this end point
    The effect of AV-101 on PVR will be measured by RHC.
    Clinical Worsening Events is defined as:
    ● Death (all causes)
    ● Hospitalization for worsening PAH
    ● Initiation of parenteral prostanoids (sc or iv infusion)
    ● ≥ 15% decline from baseline in 6MWD accompanied with continued or worsening to WHO FC III or IV symptoms.
    The decline in 6MWD must be confirmed with a repeat test on a different day within 2 weeks.
    All clinical worsening events will be adjudicated by an independent panel of clinicians experienced with PAH.
    An exploratory analysis for clinical worsening will be assessed using the criteria in the IMPRES study:
    ● Death
    ● Hospitalization for worsening PAH
    ● Worsening of WHO FC by at least one level
    ● Reduction in 6MWD by 15% from baseline confirmed on two visits
    E.5.2Secondary 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
    ● Change from baseline at Week 24 in hemodynamic measures (CI, mPAP, mRAP, and SvO2)
    ● Incidence of Clinical Worsening through 24 Weeks
    ● Achieving the multi-component improvement parameters
    - Percent of subjects who achieve the multi-component parameters by visit
    - Time to achieving the multi-component improvement parameters
    ● 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

    Other Phase 2b endpoints:
    ● Change from baseline at Week 24 in Transthoracic Echo parameters of right ventricular (RV) function.
    ● Change from baseline at Week 24 in BDI
    ● Pharmacokinetics (Cmax,ss, Cmin,ss, Cavg, Tmax,ss, AUC0-tau, CL/F,ss, MRCmax,ss, and MRAUC0-tau)
    ● Safety and tolerability

    Key Secondary Endpoints for Phase 3:
    ● Change from baseline at Week 24 in NT-proBNP
    ● Time to Clinical Worsening through 24 weeks
    ● Achieving the multi-component improvement parameters
    - Percent of subjects who achieve the multi-component parameters by visit
    - Time to achieving the multi-component improvement parameters
    ● 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

    Other Phase 3 endpoints:
    ● Change from baseline at Week 24 in Transthoracic Echo parameters of RV function
    ● Change from baseline at Week 24 in BDI
    ● Pharmacokinetics
    ● Safety and tolerability
    E.5.2.1Timepoint(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.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA43
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Austria
    Belgium
    Brazil
    Canada
    Chile
    China
    Colombia
    Czechia
    France
    Germany
    Greece
    Israel
    Italy
    Mexico
    Netherlands
    Poland
    Portugal
    Singapore
    South Africa
    Spain
    Sweden
    Turkey
    United Kingdom
    United States
    E.8.7Trial 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.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 323
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 139
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state29
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 134
    F.4.2.2In 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, Intermediate, 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
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-02-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-02-09
    P. End of Trial
    P.End of Trial StatusOngoing
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