A Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (PAH) (TROPOS).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Keros Therapeutics Inc., Keros Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

20 Mar 2024 → 13 Mar 2025

Decision date (initial)

2024-02-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Keros Therapeutics, Inc.

External identifiers

EU CT number

2022-502378-17-00

WHO UTN

U1111-1290-3167

ClinicalTrials.gov

NCT05975905

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy.

Secondary objectives 2

1. Evaluate the effect of KER-012 on exercise capacity compared to Placebo in participants on background PAH therapy.
2. Evaluate the safety and tolerability of KER-012 in participants on background PAH therapy.

Conditions and MedDRA coding

Pulmonary Arterial Hypertension

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adult participants ≥ 18 years of age.
2. Symptomatic World Health Organization (WHO) Group 1 Pulmonary Hypertension (PAH) classified by one of the following subgroups: a. Idiopathic pulmonary arterial hypertension (IPAH) b. Hereditary pulmonary arterial hypertension (HPAH) c. Associated with drugs and toxins d. PAH associated with: i. Connective tissue disease (CTD), ii. Congenital systemic-pulmonary intracardiac shunt (must have surgical correction or repair with closure device at least 1 year prior to Screening, AND have no, or clinically insignificant, shunt fraction in the opinion of Investigator [1.0 ≤ pulmonary-systemic flow ratio ≤ 1.5]).
3. Has the following hemodynamic parameters that are consistent with the diagnosis of PAH: a. Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, AND b. Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND c. PVR ≥ 5 Wood units (400 dyn·sec·cm−5). Note: RHC to assess eligibility performed within 6 weeks from Visit 1 (Day 1).
4. Has WHO/New York Heart Association (NYHA) Functional Class (FC) II or III symptoms as assessed by the Investigator at Screening and Day 1.
5. 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): a. Stable therapy is defined as no change in dose/regimen for at least 90 days prior to baseline and would be expected to be maintained for the duration of the study.
6. 6MWD ≥ 150 and ≤ 500 meters repeated twice at Screening (measured at least 4 hours apart but no longer than 1 week), and both values within 15% of each other (calculated from the highest value).
7. Provide written (signed and dated) informed consent form before the initiation of any Screening tests or procedures. Sites in Germany, check section A7-1.2 of the study protocol.

Exclusion criteria 10

1. Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease.
2. Has pulmonary function tests (PFTs) at Screening or within 180 days prior to the Screening with evidence of significant obstructive or parenchymal lung disease.
3. 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.
4. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mmHg or sitting diastolic BP > 100 mmHg at Screening.
5. Hemoglobin < 9 g/dL at Screening.
6. Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months per Investigator assessment.
7. Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis.
8. Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to baseline or planned initiation during the study.
9. Prior participation in a KER-012 study, or prior treatment with a therapy targeting TGF-β (e.g., sotatercept).
10. Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to Screening, whichever is longer. Sites in France, check section A7-1.1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in pulmonary vascular resistance (PVR) at Week 24.

Secondary endpoints 2

1. Change from Baseline in the 6-minute walk distance (6MWD) at Week 24.
2. Incidence of treatment-emergent adverse events (TEAEs), treatment-related TEAEs and discontinuations due to TEAEs; change from baseline in clinical laboratory values, vital signs, and electrocardiogram (ECG); incidence of anti-drug antibodies (ADA).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Keros Therapeutics Inc.

Sponsor organisation

Keros Therapeutics Inc.

Address

99 Hayden Avenue Suite 120 Building E

City

Lexington

Postcode

02421-7998

Country

United States

Scientific contact point

Organisation

Keros Therapeutics Inc.

Contact name

Kate Steiner, MBBS

Public contact point

Organisation

Keros Therapeutics Inc.

Contact name

Kate Steiner, MBBS

Third parties 12

Keros Therapeutics Inc.

Sponsor organisation

Keros Therapeutics Inc.

Address

1050 Waltham Street Suite 302

City

Lexington

Postcode

02421-8024

Country

United States

Third parties 12

Locations

5 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications