Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 16 for:    sotatercept
Previous Study | Return to List | Next Study

A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (SPECTRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03738150
Recruitment Status : Recruiting
First Posted : November 12, 2018
Last Update Posted : March 21, 2019
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.

Brief Summary:
This study evaluates the effect of sotatercept (ACE-011) in adults with Pulmonary Arterial Hypertension. Each eligible participant will receive standard of care (SOC) plus sotatercept (ACE-011) for a 24 week treatment period followed by a 16 week follow up period.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Biological: Sotatercept Phase 2

Detailed Description:

This is a Phase 2a, single arm, open-label, multi center exploratory study to determine the effects of sotatercept (ACE-011) plus standard of care (SOC) in adults with WHO functional class III pulmonary arterial hypertension (PAH).

All eligible participants will receive standard of care (SOC) plus sotatercept (ACE-011) at a starting dose level of 0.3 mg/kg SC for Cycle 1 and escalating to 0.7 mg/kg at cycle 2 for the remainder of the treatment period. Participants will be required to attend clinic visits once every three weeks for 24 weeks to perform one or more protocol specified evaluations. Evaluations include hemodynamic measures collected during right heart catheterization (RHC) with invasive cardiopulmonary exercise test (iCPET), and cardiac magnetic resonance imaging (MR), 6-minute walk distance (6MWD), pharmacokinetic parameters, pharmacodynamic parameters, anti-drug antibody testing, and adverse events. These assessments will be performed at the Screening Period Visit (up to 28 days before Cycle 1 Day 1), the End of Treatment Visit (Day 169), and at the End of Study Visit (Day 260).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a Single-Arm, Open-Label, Multicenter Exploratory Study to Assess the Effects of Sotatercept (ACE-011) for the Treatment of Pulmonary Arterial Hypertension
Estimated Study Start Date : March 25, 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: Sotatercept
Each participant will receive standard of care (SOC) plus sotatercept at a dose of 0.3 mg/kg SC for Cycle 1. Dose will escalate to 0.7 mg/kg SC at Cycle 2 through the remainder of the treatment period. Dosing will be every three weeks for 24 weeks.
Biological: Sotatercept
Sotatercept injection
Other Name: ACE-011




Primary Outcome Measures :
  1. Change from baseline in peak oxygen uptake (VO2 max) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]

Secondary Outcome Measures :
  1. Change from baseline in ventilatory efficiency (VE/VCO2 slope) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  2. Change from baseline in cardiac index (L/min/m2) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  3. Change from baseline in mean pulmonary arterial pressure [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  4. Change from baseline in arteriovenous O2 content difference (Ca-vO2) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  5. Change from baseline in right ventricular stroke volume (RV SV) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  6. Change from baseline in right ventricular end-systolic volume (RV ESV) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  7. Change from baseline in right ventricular end-diastolic volume (RV EDV) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  8. Change from baseline in right ventricular ejection fraction (RV EF) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  9. Change from baseline in right ventricular stroke volume index (RV SVI) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  10. Change from baseline in right ventricular stroke work index (RV SWI) (mmHg x milliliter/square meter) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  11. Change from baseline in right ventricular (RV) mass [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  12. Change from baseline in pulmonary vascular resistance (PVR) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  13. Measurement of serum concentration of sotatercept [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  14. Measurement of individual maximum sotatercept concentration (Cmax ) [ Time Frame: Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  15. Measurement of individual minimum sotatercept concentration(Cmin) [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  16. Measurement of individual average sotatercept concentration(Cavg) [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  17. Measurement of area under the concentration (AUC) versus time curve [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  18. Measurement of apparent terminal half-life (t1/2 ) [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  19. Measurement of apparent serum clearance (CL) [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  20. Measurement of apparent volume of distribution (Vd) [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  21. Measurement of absorption rate constant (Ka) [ Time Frame: Initiation of treatment (Day 1), treatment period visits (Day 43, 85, 148), end of treatment visit (Day 169), end of study visit (Day 260) ]
  22. Change from baseline in 6MWD [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  23. Change from baseline in concentration of amino-terminal brain natriuretic propeptide (NT-proBNP) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  24. Change from baseline in WHO (World Health Organization) functional class [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  25. Number of patients experiencing one or more events indicative of clinical worsening of PAH [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169)) ]
    Events that indicate clinical worsening of PAH include death, need for and/or worsening-related listing for lung and/or heart transplant, need to initiate an approved PAH SOC rescue therapy, PAH-specific hospitalization, or functional deterioration (worsened WHO Functional Class AND 15% decrease in 6MWD)

  26. Measurement of the number of adverse events (AEs) in subjects [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. 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
  3. Symptomatic pulmonary hypertension classified as WHO functional class III
  4. Screening RHC documenting a minimum PVR of ≥ 4 Wood units
  5. Pulmonary function tests within 6 months prior to Screening as follows:

    1. 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
    2. Forced expiratory volume (first second) (FEV1)/forced vital capacity (FVC) > 70% predicted
  6. 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
  7. 6MWD ≥ 100 and ≤ 550 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value
  8. Combination PAH therapy at stable (per investigator) dose levels for at least 90 days prior to Cycle 1 Day 1 (C1D1)

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

  1. 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)
  2. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to C1D1
  3. History of atrial septostomy within 180 days prior to Screening
  4. History of more than mild obstructive sleep apnea that is untreated
  5. History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to C)
  6. History of human immunodeficiency virus infection-associated PAH
  7. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536)
  8. 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
  9. Systolic BP < 90 mm Hg during Screening or at baseline
  10. History of known pericardial constriction
  11. History of personal or family history of long QTc syndrome or sudden cardiac death
  12. History of restrictive or constrictive cardiomyopathy
  13. Left ventricular ejection fraction < 45% on echocardiogram performed within 6 months of Screening OR PCWP > 15 mm Hg on RHC during baseline evaluation
  14. Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months prior to Screening)
  15. Acutely decompensated heart failure within 30 days prior to C1D1, as per investigator assessment
  16. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03738150


Contacts
Layout table for location contacts
Contact: Clinical Trials Manger 617-649-9200 clinicaltrials011@acceleronpharma.com

Locations
Layout table for location information
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Acceleron Pharma, Inc.
Investigators
Layout table for investigator information
Study Director: Janethe de Oliveira Pena, MD Acceleron Pharma, Inc.

Layout table for additonal information
Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT03738150     History of Changes
Other Study ID Numbers: A011-10
First Posted: November 12, 2018    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Acceleron Pharma, Inc.:
PAH

Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases