Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Lungs, Pulmonary, PAH, AV-101, imatinib, IMPAHCT, IMPAHCT-FUL
Brief summary
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.
Interventions
DRUGAV-101
AV-101 (imatinib) administered via dry powder inhalation
Sponsors
Aerovate Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | 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 AEs, regardless of causality is located in Reported AE section. |
Countries
Argentina, Australia, Belgium, Canada, Chile, China, Colombia, France, Germany, Israel, Italy, Latvia, Mexico, Poland, Portugal, Singapore, South Africa, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Crossover AV-101 10 mg Participants who previously received placebo in AV-101-002 received AV-101 (imatinib) 10 mg administered BID via dry powder inhalation. | 18 |
| Placebo Crossover AV-101 35 mg Participants who previously received placebo in AV-101-002 received AV-101 (imatinib) 35 mg administered BID via dry powder inhalation. | 18 |
| Placebo Crossover AV-101 70 mg Participants who previously received placebo in AV-101-002 received AV-101 (imatinib) 70 mg administered BID via dry powder inhalation. | 16 |
| Continuing AV-101 10 mg Participants who previously received AV-101 10 mg in AV-101-002 received AV-101 (imatinib) 10 mg administered BID via dry powder inhalation. | 45 |
| Continuing AV-101 35 mg Participants who previously received AV-101 35 mg in AV-101-002 received AV-101 (imatinib) 35 mg administered BID via dry powder inhalation. | 48 |
| Continuing AV-101 70 mg Participants who previously received AV-101 70 mg in AV-101-002 received AV-101 (imatinib) 70 mg administered BID via dry powder inhalation. | 41 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 2 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 | 2 | 3 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study terminated by sponsor | 17 | 17 | 14 | 40 | 45 | 37 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo Crossover AV-101 10 mg | Placebo Crossover AV-101 35 mg | Placebo Crossover AV-101 70 mg | Continuing AV-101 10 mg | Continuing AV-101 35 mg | Continuing AV-101 70 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.1 years STANDARD_DEVIATION 12.45 | 45.9 years STANDARD_DEVIATION 13.17 | 47.9 years STANDARD_DEVIATION 11.02 | 45.5 years STANDARD_DEVIATION 12.7 | 47.4 years STANDARD_DEVIATION 13.98 | 46.4 years STANDARD_DEVIATION 12.8 | 46.8 years STANDARD_DEVIATION 12.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 8 Participants | 10 Participants | 12 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 14 Participants | 12 Participants | 31 Participants | 34 Participants | 27 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 4 Participants | 2 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 8 Participants | 3 Participants | 11 Participants | 12 Participants | 9 Participants | 45 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 4 Participants | 3 Participants | 13 Participants |
| Race (NIH/OMB) White | 15 Participants | 8 Participants | 11 Participants | 27 Participants | 31 Participants | 24 Participants | 116 Participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 13 Participants | 34 Participants | 38 Participants | 35 Participants | 150 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 11 Participants | 10 Participants | 6 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 16 | 2 / 45 | 1 / 48 | 1 / 41 |
| other Total, other adverse events | 8 / 18 | 11 / 18 | 10 / 16 | 17 / 45 | 19 / 48 | 15 / 41 |
| serious Total, serious adverse events | 3 / 18 | 4 / 18 | 6 / 16 | 12 / 45 | 9 / 48 | 7 / 41 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events
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 AEs, regardless of causality is located in Reported AE section.
Time frame: From date of first dose to 30 days after date of last dose (up to approximately 21 months)
Population: The Safety Analysis Set included all participants that received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Crossover AV-101 10 mg | Number of Participants With Treatment-emergent Adverse Events | 9 Participants |
| Placebo Crossover AV-101 35 mg | Number of Participants With Treatment-emergent Adverse Events | 11 Participants |
| Placebo Crossover AV-101 70 mg | Number of Participants With Treatment-emergent Adverse Events | 12 Participants |
| Continuing AV-101 10 mg | Number of Participants With Treatment-emergent Adverse Events | 26 Participants |
| Continuing AV-101 35 mg | Number of Participants With Treatment-emergent Adverse Events | 25 Participants |
| Continuing AV-101 70 mg | Number of Participants With Treatment-emergent Adverse Events | 21 Participants |