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Trial record 4 of 21 for:    sotatercept

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03738150
Recruitment Status : Active, not recruiting
First Posted : November 13, 2018
Last Update Posted : September 20, 2021
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma Inc.

Tracking Information
First Submitted Date  ICMJE November 2, 2018
First Posted Date  ICMJE November 13, 2018
Last Update Posted Date September 20, 2021
Actual Study Start Date  ICMJE May 1, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2020)
Change from baseline in peak oxygen uptake (VO2 max) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
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) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2020)
  • Change from baseline in ventilatory efficiency (VE/VCO2 slope) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in cardiac index (L/min/m2) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in mean pulmonary arterial pressure [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in arteriovenous O2 content difference (Ca-vO2) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in right ventricular stroke volume (RV SV) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in right ventricular end-systolic volume (RV ESV) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in right ventricular end-diastolic volume (RV EDV) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in right ventricular ejection fraction (RV EF) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in right ventricular stroke volume index (RV SVI) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in right ventricular (RV) mass [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in pulmonary vascular resistance (PVR) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of serum concentration of sotatercept [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of individual maximum sotatercept concentration (Cmax ) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of individual minimum sotatercept concentration(Cmin) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of individual average sotatercept concentration(Cavg) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of area under the concentration (AUC) versus time curve [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of apparent terminal half-life (t1/2 ) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of apparent serum clearance (CL) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of apparent volume of distribution (Vd) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Measurement of absorption rate constant (Ka) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in 6MWD [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in concentration of amino-terminal brain natriuretic propeptide (NT-proBNP) [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Change from baseline in WHO (World Health Organization) functional class [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
  • Number of patients experiencing one or more events indicative of clinical worsening of PAH [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 34 (each cycle is 21 days) ]
    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)
  • Measurement of the number of adverse events (AEs) in subjects [ Time Frame: From initiation of treatment Cycle 1 Day 1 to the end of Cycle 9 (each cycle is 21 days). ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
  • 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) ]
  • 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) ]
  • Change from baseline in mean pulmonary arterial pressure [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Change from baseline in right ventricular (RV) mass [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  • Change from baseline in pulmonary vascular resistance (PVR) [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Change from baseline in 6MWD [ Time Frame: From initiation of treatment (Day 1) to the end of treatment visit (Day 169) ]
  • 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) ]
  • 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) ]
  • 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)
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension
Official Title  ICMJE 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
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 an 18 month Extension Period and an 8 week follow up period.
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 the 24 week Treatment Period and once every three weeks for the 18 month Extension Period 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Biological: Sotatercept
Sotatercept injection
Other Name: ACE-011
Study Arms  ICMJE 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 during the 24 weeks Treatment Period and every three weeks during the 18 month Extension Period.
Intervention: Biological: Sotatercept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 19, 2021)
21
Original Estimated Enrollment  ICMJE
 (submitted: November 8, 2018)
25
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
    3. 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.
  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. Electrocardiogram (ECG) with QTcF > 480 msec during Screening or C1D1
  12. History of personal or family history of long QTc syndrome or sudden cardiac death
  13. History of restrictive or constrictive cardiomyopathy
  14. Left ventricular ejection fraction < 45% on echocardiogram performed within 6 months of Screening OR PCWP > 15 mm Hg on RHC during baseline evaluation
  15. 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)
  16. Acutely decompensated heart failure within 30 days prior to C1D1, as per investigator assessment
  17. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03738150
Other Study ID Numbers  ICMJE A011-10
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Acceleron Pharma Inc.
Study Sponsor  ICMJE Acceleron Pharma Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jonathan Lu, MD Acceleron Pharma Inc.
PRS Account Acceleron Pharma Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP