A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension

NCT03738150 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: A011-107962-002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

Brief Summary

This study evaluates the effect of sotatercept (ACE-011) in adults with pulmonary arterial hypertension (PAH). Each eligible participant will receive standard of care (SOC) plus sotatercept (ACE-011) for a 24-week treatment period, followed by an 18-month extension period, and an 8-week follow-up period.

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks

  Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks.

  Baseline and 24 weeks

Secondary Outcomes (25)

• Change From Baseline in Right Ventricular Stroke Volume (RV SV) at 24 Weeks

  Baseline and 24 weeks

• Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks

  Baseline and 24 weeks

• Change From Baseline in Right Ventricular End-Diastolic Volume (RV EDV) at 24 Weeks

  Baseline and 24 weeks

• Percent Change From Baseline in Right Ventricular Ejection Fraction (RV EF) at 24 Weeks

  Baseline and 24 Weeks

• Change From Baseline in Right Ventricular Stroke Volume Index (RV SVI) at 24 Weeks

  Baseline and 24 weeks

Study Arms (1)

Sotatercept

EXPERIMENTAL

Each participant will receive SOC plus sotatercept at a dose of 0.3 mg/kg SC for Cycle 1. (Each cycle will be 21 days.) From Cycle 2 through Cycle 9, the dose will be escalated to 0.7 mg/kg SC. Dosing will be every three weeks during the 24-week treatment period and 18-month extension period.

Biological: Sotatercept; Other: SOC

Interventions

Sotatercept BIOLOGICAL

Sotatercept injection

Also known as: ACE-011

Sotatercept

SOC OTHER

SOC therapy refers to combination therapy consisting of drugs from two or more of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist.

Sotatercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Documented findings on RHC at any time prior to Screening consistent with a diagnosis of World Health Organization (WHO) pulmonary hypertension Group 1: PAH of any of the following subtypes:
• Idiopathic PAH
• Heritable PAH
• Drug- or toxin-induced PAH
• PAH associated with connective tissue disease
• PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair
• Symptomatic pulmonary hypertension classified as WHO functional class III
• Screening RHC documenting a minimum PVR of ≥ 4 Wood units
• Pulmonary function tests within 6 months prior to Screening as follows:
• Total lung capacity \> 70% predicted; or if between 60% to 70% predicted, or not possible to be determined, confirmatory high-resolution computed tomography (CT) indicating no more than mild interstitial lung disease per investigator interpretation or
• Forced expiratory volume (first second) (FEV1)/forced vital capacity (FVC) \> 70% predicted
• For subjects with a history of lobectomy or pneumonectomy, and for whom there are no population-based normalization methods, assessment based on residual lung volume will be permitted to assess eligibility.
• Ventilation-perfusion (VQ) scan (or, if unavailable, a negative CT pulmonary angiogram \[CTPA\] or pulmonary angiography result), any time prior to Screening or conducted during Screening Period with normal or low probability result
• MWD ≥ 100 and ≤ 550 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value

You may not qualify if:

• Participants will be excluded from the study if they meet any of the following criteria:
• Started or stopped receiving any general supportive therapy for pulmonary hypertension (e.g., diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to C1D1 (Cycle 1 Day 1)
• Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to C1D1
• History of atrial septostomy within 180 days prior to Screening
• History of more than mild obstructive sleep apnea that is untreated
• History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to C)
• History of human immunodeficiency virus infection-associated PAH
• Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536)
• Uncontrolled systemic hypertension as evidenced by sitting systolic BP \> 160 mm Hg or sitting diastolic BP \> 100 mm Hg during Screening after a period of rest
• Systolic BP \< 90 mm Hg during Screening or at baseline
• History of known pericardial constriction
• Electrocardiogram (ECG) with QTcF \> 480 msec during Screening or C1D1
• History of personal or family history of long QTc syndrome or sudden cardiac death
• History of restrictive or constrictive cardiomyopathy
• Left ventricular ejection fraction \< 45% on echocardiogram performed within 6 months of Screening OR pulmonary capillary wedge pressure (PCWP) \> 15 mm Hg on RHC during baseline evaluation

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (4)

The University of Arizona

Tucson, Arizona, 85724, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Waxman AB, Systrom DM, Manimaran S, de Oliveira Pena J, Lu J, Rischard FP. SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension. Circ Heart Fail. 2024 May;17(5):e011227. doi: 10.1161/CIRCHEARTFAILURE.123.011227. Epub 2024 Apr 4.

  PMID: 38572639 RESULT

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

• Jonathan Lu, MD

  Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: November 13, 2018
• Study Start: April 19, 2019
• Primary Completion: December 21, 2021
• Study Completion: March 22, 2022
• Last Updated: August 27, 2024
• Results First Posted: February 10, 2023

Record last verified: 2024-07

Locations

US (4)