Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary arterial hypertension [PAH]
Brief summary
Study KER-012-A201 is Phase 2, double-blind, randomized, placebo-controlled study to determine the efficacy and safety of KER-012 compared to Placebo in adults with PAH (WHO Group 1 PH) on stable background PAH therapy. The study is divided into the Screening Period, Treatment Period, Extension Period, and Follow-Up Period.
Detailed description
This is a randomized, phase 2, double-blind, placebo-controlled study of KER-012 in combination with background therapy in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 2:2:2:3 ratio to receive KER-012 (Dose A), KER-012 (Dose B), KER-012 (Dose C), or placebo by subcutaneous injection (SC) every 4 weeks for a period of 24 weeks in the placebo-controlled treatment period of the study while on background therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and safety parameters. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 72-week extension period in which KER-012 treated participants will continue to receive their same assigned dose level from the treatment period every 4 weeks and placebo treated participants will receive KER-012 (Dose B) every 4 weeks while on background therapy.
Interventions
BIOLOGICALDose A KER-012
Dose A KER-012 (Q4W);
BIOLOGICALDose B KER-012
Dose B KER-012 (Q4W);
BIOLOGICALDose C KER-012
Dose C KER-012 (Q4W);
BIOLOGICALPlacebo for 24 Weeks followed by Dose B KER-012 for 72 weeks
Treatment Period (24 weeks): Placebo SC (Q4W) Extension Period (72 weeks after Placebo treatment): KER-012 (Dose B) SC (Q4W)
Sponsors
Keros Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study in which treatment assignment will be blinded for the Investigators and any personnel (other than the unblinded pharmacist or designee) involved with the study conduct or evaluation at the investigational sites, the CRO, and the Sponsor.
Intervention model description
Participants will be randomly assigned in a 2:2:2:3 ratio to 1 of 4 treatment arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants ≥ 18 years of age * Symptomatic World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH)(PAH) classified by one of the following subgroups: * Idiopathic pulmonary arterial hypertension (IPAH); * Heritable pulmonary arterial hypertension (HPAH); * Associated with drugs and toxins; * PAH associated with: * Connective tissue disease * Congenital systemic-pulmonary intracardiac shunt * Has the following hemodynamic parameters that are consistent with the diagnosis of PAH: * Mean pulmonary arterial pressure (mPAP) \> 20 mmHg at rest, AND * Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND * PVR ≥ 5 Wood Units (400 dyn·sec·cm-5) * Has WHO/New York Heart Association (NYHA) Functional Class (FC) II or III symptoms as assessed by the Investigator * Must be on a stable PAH background therapy with either an endothelin-receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE5-I) or soluble guanylate cyclase (sGC) stimulator and/or prostacyclin analogue or receptor agonist (oral/inhaled/SC/intravenous) * 6MWD ≥ 150 and ≤ 500 meters at screening * Provide written (signed and dated) informed consent form before the initiation of any Screening tests or procedures
Exclusion criteria
* Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease * Has pulmonary function tests (PFTs) with evidence of significant obstructive or parenchymal lung disease * Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or other local standard of care diagnostic evaluation at the time of PAH diagnosis or after * Has uncontrolled systemic hypertension * Hemoglobin \< 9 g/dL at Screening * Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of \< 12 months per Investigator assessment * Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis * Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study * Prior participation in a KER-012 study or prior treatment with a therapy targeting TGF-β superfamily (e.g. sotatercept) * Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to Screening, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PVR (Pulmonary Vascular Resistance) | Baseline and Week 24 | Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 6MWD | Through week 24 (primary treatment period) | Evaluate the effect of KER-012 on exercise capacity compared to Placebo in participants on background PAH therapy |
| Evaluate Improvement in Functional Assessment of KER-012 Compared to Placebo in Participants on Background PAH Therapy | Up to week 24 (primary treatment period) | Proportion of participants who achieved improvement from Baseline in NYHA FC/WHO at week 24. Improvement in WHO/NYHA FC (World Heath Association/New York Heart Association functional class) was defined as a decreased in functional class from baseline or maintenance of WHO/NYHA = 2 from baseline. |
| Evaluate the Changes From Baseline in the Concentration of the PAH Biomarker, NT-proBNP in Blood Samples | Up to week 24 (primary treatment period) | Change from Baseline in NT-proBNP at week 24 |
Countries
Australia, Brazil, France, Germany, Poland, Portugal, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 41 clinical study centers in Australia, Brazil, France, Germany, Poland, Portugal, Spain, Taiwan, South Korea, the United Kingdom, and the United States.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.2 Years STANDARD_DEVIATION 15.88 |
| Age, Customized Median (Q1, Q3) | 45.0 Years |
| Age, Customized 65 to 74 years | 2 Participants |
| Age, Customized < 65 years | 100 Participants |
| Age, Customized ≥ 75 years | 3 Participants |
| BMI (kg/m2) ≥ 18.5 to < 25 (Normal weight) | 36 Participants |
| BMI (kg/m2) < 18.5 (Underweight) | 3 Participants |
| BMI (kg/m2) ≥ 25 to < 30 (Overweight) | 16 Participants |
| BMI (kg/m2) ≥ 30 (Obesity Class I) | 10 Participants |
| BMI (kg/m2) | 24.90 kg/m2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Height (cm) | 164.0 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 97 Participants |
| Sex/Gender, Customized Female | 83 Participants |
| Sex/Gender, Customized Female with childbearing potential | 9 Participants |
| Sex/Gender, Customized Female without childbearing potential | 11 Participants |
| Sex/Gender, Customized Male | 5 Participants |
| Weight (kg) | 75.50 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 1 / 25 | 1 / 25 | 1 / 39 |
| other Total, other adverse events | 10 / 24 | 9 / 25 | 7 / 25 | 6 / 39 |
| serious Total, serious adverse events | 2 / 24 | 3 / 25 | 9 / 25 | 5 / 39 |
Outcome results
None listed