NCT05557942: IMPAHCT-FUL

Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial - Follow Up Long Term Extension (IMPAHCT-FUL)

Terminated Phase 3 Results posted Last updated 10 October 2024

What this trial tests

Phase 3 trial testing AV-101 in Pulmonary Arterial Hypertension in 186 participants. Terminated before completion.

Timeline

2 November 2022

Primary endpoint
8 August 2024

8 August 2024

Quick facts

Lead sponsor	Aerovate Therapeutics
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	186
Start date	2 November 2022
Primary completion	8 August 2024
Estimated completion	8 August 2024
Sites	72 locations across Italy, Colombia, Poland, Belgium, Mexico, Portugal, United States, Latvia

Drugs / interventions tested

• AV-101 — full drug profile →

Conditions studied

• Pulmonary Arterial Hypertension — all drugs for Pulmonary Arterial Hypertension →

Sponsor

Aerovate Therapeutics

Who can join

Adults 18 to 75, any sex, with Pulmonary Arterial Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events Primary · From date of first dose to 30 days after date of last dose (up to approximately 21 months)

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious Adverse Events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious

Group	Value	95% CI
Placebo Crossover AV-101 10 mg	9
Placebo Crossover AV-101 35 mg	11
Placebo Crossover AV-101 70 mg	12
Continuing AV-101 10 mg	26
Continuing AV-101 35 mg	25
Continuing AV-101 70 mg	21

Adverse events — posted to ClinicalTrials.gov

Time frame: From date of first dose to date of last dose plus 30 days (up to approximately 21 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Crossover AV-101 10 mg

Serious: 3/18 (17%)

Deaths: 0/18

Placebo Crossover AV-101 35 mg

Serious: 4/18 (22%)

Deaths: 0/18

Placebo Crossover AV-101 70 mg

Serious: 6/16 (38%)

Deaths: 0/16

Continuing AV-101 10 mg

Serious: 12/45 (27%)

Deaths: 2/45

Continuing AV-101 35 mg

Serious: 9/48 (19%)

Deaths: 1/48

Continuing AV-101 70 mg

Serious: 7/41 (17%)

Deaths: 1/41

Serious adverse events (34 terms)

Reaction	System	Placebo Crossover AV-101 1…	Placebo Crossover AV-101 3…	Placebo Crossover AV-101 7…	Continuing AV-101 10 mg	Continuing AV-101 35 mg	Continuing AV-101 70 mg
Right ventricular failure	Cardiac disorders	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Iron deficiency anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—	—	—
Cardiac failure acute	Cardiac disorders	—	—	—	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—	—	—	—
Ventricular arrhythmia	Cardiac disorders	—	—	—	—	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—	—	—	—	—
Enteritis	Gastrointestinal disorders	—	—	—	—	—	—
Haematochezia	Gastrointestinal disorders	—	—	—	—	—	—
Catheter site haemorrhage	General disorders	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—
Acute sinusitis	Infections and infestations	—	—	—	—	—	—
Atypical pneumonia	Infections and infestations	—	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—	—
Perineal abscess	Infections and infestations	—	—	—	—	—	—
Pulmonary tuberculosis	Infections and infestations	—	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Septic shock	Infections and infestations	—	—	—	—	—	—
Vascular device infection	Infections and infestations	—	—	—	—	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—	—	—	—	—
Bone lesion	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—

Other adverse events (97 terms — click to expand)

Reaction	System	Placebo Crossover AV-101 1…	Placebo Crossover AV-101 3…	Placebo Crossover AV-101 7…	Continuing AV-101 10 mg	Continuing AV-101 35 mg	Continuing AV-101 70 mg
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Chest discomfort	General disorders	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Oxygen saturation decreased	Investigations	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Iron deficiency	Metabolism and nutrition disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Palpitations	Cardiac disorders	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Atypical pneumonia	Infections and infestations	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—
Bronchitis bacterial	Infections and infestations	—	—	—	—	—	—
Clostridium difficile colitis	Infections and infestations	—	—	—	—	—	—
Otitis media acute	Infections and infestations	—	—	—	—	—	—
Serratia sepsis	Infections and infestations	—	—	—	—	—	—
Transmission of an infectious agent via transplant	Infections and infestations	—	—	—	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Throat irritation	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Dyspnoea at rest	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Nasal dryness	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—

Most-reported serious reactions: Right ventricular failure, Influenza, Pneumonia, Iron deficiency anaemia, Cardiac failure, Cardiac arrest, Cardiac failure acute, Supraventricular tachycardia.

Data from ClinicalTrials.gov NCT05557942 adverse events section.

Sponsor's own description

IMPAHCT-FUL: Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial - Follow Up Long Term Extension (LTE) Trial was a follow up study to establish the long-term safety of AV-101. Subjects who successfully completed the 24-week placebo-controlled parent trial (AV-101-002, NCT#05036135) were offered the opportunity to continue into this LTE study. Subjects who enrolled in the study were to receive one of three active AV-101 doses until such time as the optimal dose was selected in the parent study.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Novel Molecular Mechanisms Involved in the Medical Treatment of Pulmonary Arterial Hypertension.
   Martin de Miguel I, Cruz-Utrilla A, Oliver E, Escribano-Subias P. · · 2023 · cited 11× · PMID 36835558 · DOI 10.3390/ijms24044147
2. IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension.
   Gillies H, Chakinala MM, Dake BT, Feldman JP, et al · · 2024 · cited 10× · PMID 38532768 · DOI 10.1002/pul2.12352
3. Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs.
   Jin Q, Chen D, Zhang X, Zhang F, et al · · 2023 · cited 8× · PMID 37376028 · DOI 10.3390/pharmaceutics15061579
4. Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.
   Zuo Y, Li B, Gao M, Xiong R, et al · · 2024 · cited 7× · PMID 38555425 · DOI 10.1186/s12931-024-02772-8
5. Future Perspectives of Pulmonary Arterial Hypertension: A Review of Novel Pipeline Treatments and Indications.
   Novara ME, Di Martino E, Stephens B, Nayrouz M, et al · · 2024 · cited 6× · PMID 38514585 · DOI 10.1007/s40268-024-00453-x
6. State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment.
   Shafeghat M, Raza Y, Catania R, Rahsepar AA, et al · · 2025 · cited 3× · PMID 40722843 · DOI 10.3390/biomedicines13071773
7. Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.
   Jasińska-Stroschein M, Glajzner P. · · 2024 · cited 3× · PMID 39684570 · DOI 10.3390/ijms252312858