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).
- Conditions
- Pulmonary Arterial Hypertension (PAH)Pulmonary Arterial Hypertension
- Registration Number
- NL-OMON54466
- Lead Sponsor
- Aerovate Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 14
To be eligible, a participant is required to be or have:
1• Male or female adults between 18 and 75 years of age at the screening visit
within 28 days
prior to Day 1.
2• Subject 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• Meets all of the following hemodynamic criteria by means of an RHC at study
Screening: mPAP
>= 25 mmHg, PVR > 400 dynes.sec/cm5 and PCWP <= 15 mmHg.
* For the Phase 2b part: subjects who have had an RHC within 30 days of
the Screening visit
to assess for pulmonary hypertension, with all the protocol required
variables collected, and
was performed at the same institution as the Investigator*s site do
not require the
Screening/Baseline RHC to be performed.
* For the Intermediate and Phase 3 Parts: RHC procedures performed
within 12-months of
screening may be accepted provided the subject meets the Inclusion
Criteria #5
requirements for stable background PAH medication.
5• On a stable background of at least two PAH approved medications at the
Screening Visit,
i.e., the same PAH medications for at least 90 days and each PAH
medication at a stable
dose for at least 30 days. Approved PAH medications include
phosphodiesterase type 5
(PDE-5) inhibitors, endothelin receptor antagonists (ERA), soluble
guanylate cyclase
(sGC) stimulators, and parenteral and oral prostacyclins (including
prostanoids and prostacyclin
receptor agonists). Stability of parenteral prostacyclins means a change
of no more than 10% in
the previous 30 days from the Screening Visit.
6• A history of ventilation/perfusion (V/Q) scan, CT angiogram or pulmonary
arteriogram negative
for chronic thromboembolic pulmonary hypertension (CTEPH) at the time
of their Group 1 PAH
diagnosis (if results from a historical scan are unavailable then one
of the specified imaging
procedures may be performed at Screening).
7• Must meet all of the following criteria for pulmonary function (spirometry)
tests completed no
more than 24 weeks before the Screening Visit: Forced Expiratory Volume
in 1 second (FEV1)
>= 60% of predicted normal and FEV1:Forced Vital Capacity (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 tests. In addition, the subject must be able to
demonstrate a stable baseline for
the 6-minute walk tests between the Screening and Randomization
Visits.
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 agr
1• Taking warfarin (or any vitamin K antagonists), direct oral anticoagulant
(DOAC) therapy, or
dual antiplatelet therapy within 2 weeks prior to Day 1/Randomization
2• Pulmonary hypertension (PH) belonging to Groups 2 to 5 of the 2018 NICE
classification and
Group 1 diagnosed with Portopulmonary Hypertension.
3• 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.
4• Evidence of three or more (>= 3) of the following left ventricular
disease/dysfunction risk factors:
o Body mass index (BMI) >= 30 kg/m2 at the Screening Visit
o History of essential hypertension
o Diabetes mellitus - any type
o Historical evidence of significant coronary artery disease (CAD)
established by any one of
the following:
- History of myocardial infarction
- History of percutaneous coronary intervention (PCI)
- Angiographic evidence of CAD (> 50% stenosis in at least one
vessel), by
angiography
- Positive stress test with imaging
- Previous coronary artery surgery
- 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 on 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 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. (If there is prolongation of the QTcF
interval in the presence of
bundle branch block, the Investigator should use their clinical
judgement as to whether to
include the subject. These cases should be discussed with the Medical
Monitor).
14• History of Long QT Syndrome or Torsade de Pointes
15• Hemoglobin of < 80 g/L (8 g/dL) at the Screening Visit
16• Serum ALT or AST lab value that is >3 x upper limit of normal (ULN) at the
Screening Visit
17• Severe renal impairment (eGFR <30 mL/min/1.73 m^2 at screening based on the
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 2b<br /><br>* Placebo corrected change from baseline at Week 24 in PVR, as measured by RHC<br /><br>in subjects with PAH<br /><br><br /><br>Phase 3<br /><br>* Placebo corrected change from baseline at Week 24 in the 6MWD</p><br>
- Secondary Outcome Measures
Name Time Method