Clinical Trials Register

Summary
EudraCT Number:	2021-003020-32
Sponsor's Protocol Code Number:	A01116
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-10-15
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2021-003020-32

A.3

Full title of the trial

Phase 2, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of Sotatercept versus Placebo-Controlled for the Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) due to Heart Failure with Preserved Ejection Fraction (HFpEF)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 2 Study of Sotatercept for Combined Postcapillary and Precapillary Pulmonary Hypertension Treatment

A.3.2

Name or abbreviated title of the trial where available

A Phase 2 Study of Sotatercept for Cpc-PH Treatment

A.4.1

Sponsor's protocol code number

A01116

A.5.4

Other Identifiers

Name:

IND

Number:

154471

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ, USA
B.5.2	Functional name of contact point	Alexandra Cornell
B.5.3	Address:
B.5.3.1	Street Address	126 East Lincoln Ave., P.O. Box 2000
B.5.3.2	Town/ city	Rahway
B.5.3.3	Post code	NJ 07065
B.5.3.4	Country	United States
B.5.4	Telephone number	0016179923648
B.5.6	E-mail	alexandra.cornell@merck.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sotatercept
D.3.2	Product code	ACE-011 / MK-7962
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SOTATERCEPT
D.3.9.1	CAS number	1001080-50-7
D.3.9.2	Current sponsor code	ACE-011 / MK-7962
D.3.9.3	Other descriptive name	SOTATERCEPT
D.3.9.4	EV Substance Code	SUB179718
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Combined Postcapillary and Precapillary Pulmonary Hypertension (Cpc-PH) due to Heart Failure with Preserved Ejection
Fraction (HFpEF)

E.1.1.1

Medical condition in easily understood language

Combined Postcapillary and Precapillary Pulmonary Hypertension due to Heart Failure

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10037400
E.1.2	Term	Pulmonary hypertension
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy: This study is designed to evaluate the efficacy, measured by change from baseline in
PVR (primary endpoint) and 6MWD (key secondary endpoint) of sotatercept versus placebo in
adults with Cpc-PH due to HFpEF.
Safety: The safety and tolerability of sotatercept versus placebo in adults with Cpc-PH due to
HFpEF will be assessed by the safety endpoints listed below.

E.2.2

Secondary objectives of the trial

Not Applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants must meet the following criteria to be enrolled in this study:
1. Age 18 to 85 years
2. Clinical diagnosis of HFpEF:
• Left ventricular ejection fraction ≥ 50%, with no history of LVEF below 45% in more than 2 consecutive measurements under stable conditions
3. Demonstrated Cpc-PH by all of the following:
• Baseline RHC performed within 28 days of randomization documenting a minimum PVR ≥ 320 dyn•sec/cm5 (4 wood units) (see Section 9.2.1 for historic RHC requirements)
• Mean pulmonary arterial pressure > 20 mmHg
• Pulmonary capillary wedge pressure > 15 mmHg but < 30 mmHg
4. New York Heart Association FC of II or III
5. Six minute Walk Distance ≥ 100 meters repeated twice during Screening and both values
within 15% of each other, calculated from the highest value (see Section 9.3.2 for details)
6. Chronic medication for HF or for any underlying condition, administered at a stable (per
investigator) dose for ≥ 30 days prior to Visit 1. Diuretics and/or anticoagulants are
excepted from this rule but should not be newly started or stopped within 30 days of
Visit 1, and a prescribed dose change should not occur within 7 days of Visit 1.
Anticoagulation may be suspended for RHC if necessary.
7. Women of childbearing potential (defined in Appendix 2) must:
• Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug
• If sexually active, with a male partner:
- Use highly effective
contraception without interruption, for at least 28 days prior to starting the
investigational product, AND
- Agree to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions), and for
16 weeks (112 days) after discontinuation of study treatment
• Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration
of the study and for at least 16 weeks (112 days) after the last dose of study drug
See Appendix 2 for additional contraceptive information.
8. Male participants must:
• Agree to use a condom, defined as a male latex condom or non-latex condom NOT
made out of natural (animal) membrane (e.g., polyurethane), during sexual contact
with a pregnant female or a WOCBP while participating in the
study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful
vasectomy (see Appendix 2 for additional contraceptive information)
• Refrain from donating blood or sperm for the duration of the study and for 16 weeks
(112 days) after the last dose of study drug
9. Ability to adhere to the study visit schedule and understand and comply with all protocol
requirements
10. Agreement to not participate in any other trials of investigational drugs/devices while
enrolled in the A011-16 study
11. Ability to understand and provide documented informed consent for participation

E.4

Principal exclusion criteria

1. A diagnosis of PH in WHO Group 1, WHO Group 3, WHO Group 4, or WHO Group 5
2. Clinically significant and active lung disease:
- Chronic obstructive pulmonary disease with post-bronchodilator forced expiratory volume in the first second (FEV1) < 60% predicted
- Restrictive lung disease with total lung capacity < 70% predicted
- More than mild interstitial lung disease (ILD), with FVC < 70% or FEV1 < 60% predicted (still appropriate if absence of more than mild ILD, fibrosis or COPD on computed tomography [CT] imaging)
3. Cardiovascular comorbidities, which include any of the following:
-History of more than mild mitral or aortic stenosis (corrected mitral or
aortic stenosis by a surgical or transcatheter method within 12 months
from Visit 1 and no more than mild residual stenosis may be allowed
after the Medical Monitor's review)
-Ongoing more than mild mitral or aortic regurgitation (corrected mitral
or aortic regurgitation by a surgical or transcatheter method within 12
months from Visit 1 and no more than mild residual regurgitation may be allowed after the Medical Monitor's review). NOTE: if an imaging report reads 'mild-to-moderate mitral regurgitation', the participant may still be enrolled if, in the opinion of the
investigator, the mitral regurgitation is no more than mild.
-More than one valve replacement or repair (mechanical or
biomechanical) or anticipation of any valve replacement or repair.
-Severe tricuspid regurgitation due to primary valvular disease (e.g.,
from endocarditis, carcinoid, or mechanical destruction).
- Occurrence of myocardial infarction, acute coronary syndrome,
coronary artery bypass graft or percutaneous coronary intervention
within 180 days of Visit 1
- History of serious life-threatening or hemodynamically significant
arrhythmia
- History of or anticipated heart transplant or ventricular assist device
implantation
- History of implantable cardioverter defibrillator placement or
anticipated implantation of pacemaker, pacemaker implantation within
30 days of Screening
- History of known pericardial constriction, hypertrophic
cardiomyopathy, sarcoidosis, or amyloid cardiomyopathy
- Uncontrolled systemic hypertension as evidenced by sitting systolic
blood pressure > 160 mmHg or sitting diastolic blood pressure > 110
mmHg during Screening after a period of rest
- Systemic hypotension as evidenced by sitting systolic blood pressure <
90 mmHg or sitting diastolic blood pressure < 50 mmHg during
Screening
- Resting heart rate of < 45 bpm or > 115 bpm (including atrial
fibrillation)
- Stroke within 90 days of Visit 1
- Acutely decompensated HF that required hospitalization within 30 days
of Visit 1
- Electrocardiogram during Screening Period with Fridericia's corrected
QT interval (QTcF) > 470 msec for males or > 480 msec for females, or >
500 msec if a ventricular conduction defect (right bundle branch block;
left bundle branch block; or interventricular conduction delay) is present
- Personal or family history of Brugada syndrome, sudden cardiac arrest
or unexplained sudden cardiac death or arrest
- Personal or family history of long QT syndrome unless the subject's
ECG shows a normal QTc
- Arrhythmogenic right ventricular dysplasia (ARVD) unless the subject
has a recent cardiac MRI that shows no evidence of this diagnosis.
4. Hospitalization for any worsening of medical conditions or any significant surgery per investigator within 30 days of Visit 1.
5. Received any approved PAH-specific therapies (i.e., endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase-5 inhibitors, or a soluble guanylate cyclase stimulators) within 30 days of Visit 1. The use of an oral phosphodiesterase type 5 inhibitor, if only indicated for erectile dysfunction, is permitted, if not administered within 48 hours of a study visit or procedure.
6. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin or levosimendan) within 30 days of Visit 1
7. Received erythropoietin within 6 months of Visit 1
8. Known history of chronic liver disease, including untreated hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), with severe hepatic impairment and/or cirrhosis (e.g., hepatic encephalopathy)
9. Prior exposure to sotatercept or luspatercept
10. Currently enrolled in or have completed any other investigational product study within
30 days for small-molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented consent
11. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days of Visit 1 or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are
eligible)

Please refer to the study protocol Section 7.2. for all exclusion criteria

E.5 End points

E.5.1

Primary end point(s)

Efficacy Endpoints
Primary Efficacy Endpoint
• Change from baseline in PVR at Week 24

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline at Week 24

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint
• Change from baseline in 6MWD at Week 24
Secondary Endpoints
• Time to first clinical worsening event (TTCW) assessed at Week 24 and separately for all available follow-up after Week 24, defined as the number of weeks from first dose date to any of the following:
− Hospitalization due to a cardiopulmonary indication (a non-elective
hospitalization lasting at least 24 hours in duration caused by clinical conditions
directly related to PH and/or HF)
− Administration of intravenous diuretics or SC furosemide
− Death (all causes)
− Decrease in 6MWD by ≥ 15% from baseline confirmed by 2 tests at least 4 hours,
but no more than 6 weeks, apart
• Change from baseline in hemodynamic and echocardiography (ECHO) parameters, including but
not limited to PVR, mean pulmonary arterial pressure (mPAP), pulmonary capillary
wedge pressure (PCWP), TAPSE, right ventricular fractional area change (RVFAC),
LVEF, IVRT, ratio of mitral inflow velocity I to mitral annular velocty (e') (E/e' ratio), ratio of the peak velocity flow of the E wave in early
diastole to peak velocity flow of the A wave in late diastole (E/A ratio) and myocardial contraction fraction (MCF) at Week 24
• Change from baseline in NT-proBNP at Week 24
• Change from baseline in NYHA FC at Week 24
• Change from baseline in 6MWD at Week 48
• Change from baseline in hemodynamic and ECHO parameters, including but not limited to PVR, mPAP, PCWP, TAPSE, RVFAC, LVEF, IVRT, E/e' ratio, and E/A ratio and MCF at Week 48
• Change from baseline in NT-proBNP at Week 48
• Change from baseline in NYHA FC at Week 48
• Change from baseline in PVR, 6MWD, and NYHA FC at Week 48 in the Extension
Period in the placebo-crossed Treatment Group
• Change from Week 24 in PVR, 6MWD, and NYHA FC at Week 48 in the Extension
Period in the placebo-crossed Treatment Group

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline in 6MWD at Week 24

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Israel

Mexico

United Kingdom

United States

Belgium

France

Germany

Italy

Poland

Spain

Sweden

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

113

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-12-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-12-29

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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