Clinical Trials Register

Summary
EudraCT Number:	2018-004887-74
Sponsor's Protocol Code Number:	AC-065D301
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-06-03
Trial 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

UK - MHRA

A.2

EudraCT number

2018-004887-74

A.3

Full title of the trial

A Multicenter, Randomized, Double-blind, Placebo-controlled Study in
Participants with Sarcoidosis-associated Pulmonary Hypertension (SAPH)
to Assess the Efficacy and Safety of Oral Selexipag.

A.3.1

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

A study of the effectiveness and safety of selexipag in patients with sarcoidosis-associated pulmonary hypertension.

A.4.1

Sponsor's protocol code number

AC-065D301

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	Actelion Pharmaceuticals Ltd
B.1.3.4	Country	Switzerland
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	Actelion Pharmaceuticals Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715242166
B.5.5	Fax number	+31715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	Yes
D.2.1.1.1	Trade name	Uptravi
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Selexipag
D.3.2	Product code	ACT-293987 / JNJ-67896049
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SELEXIPAG
D.3.9.2	Current sponsor code	ACT-293987 / JNJ-67896049
D.3.9.3	Other descriptive name	SELEXIPAG
D.3.9.4	EV Substance Code	SUB130805
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

sarcoidosis-associated pulmonary hypertension (SAPH)

E.1.1.1

Medical condition in easily understood language

Elevated pressure in lung vessels due to sarcoidosis (i.e. sarcoidosis-associated pulmonary hypertension [SAPH])

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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

To assess the effect of selexipag versus placebo on pulmonary vascular resistance (PVR) in participants with sarcoidosis-associated pulmonary hypertension (SAPH) up to Week 26.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
2. Male or female.
3. 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age, inclusive, at Screening.
4. Confirmed diagnosis of sarcoidosis as per ATS criteria.
5. Sarcoidosis-associated precapillary PH, confirmed by RHC (at rest) within 90 days prior to randomization:
a. PVR ≥320 dyn*sec/cm5 (≥4.0 Wood units)
b. Mean pulmonary artery pressure (mPAP) ≥25 mmHg
c. Pulmonary artery wedge pressure (PAWP) ≤15 mm Hg, or if not available or unreliable, a left ventricular end diastolic pressure (LVEDP) ≤15 mmHg.
6. PH severity according to modified WHO FC II–IV at Screening and randomization; participants of WHO FC IV must be in a stable condition and able to perform a 6MWT.
7. Criterion modified per Amendment 2.
7.1 Either not receiving PH-specific treatment, or receiving PH-specific oral monotherapy (ie, riociguat or PDE5i or ERA); if on oral PH-specific monotherapy then treatment had to be stable (i.e. no introduction of new therapies or changes in dose) for at least 90 days prior to both the RHC qualifying for enrollment and randomization.
8. Criterion modified per Amendment 2.
8.1 Stable sarcoidosis treatment regimen, ie, no new specific anti-inflammatory treatment for sarcoidosis for at least 90 days, and stable dose(s) for at least 30 days prior to both the RHC qualifying for enrollment and randomization.
9. 6MWD between 50 and 450m both at Screening and at the time of randomization.
10. Forced vital capacity (FVC) >50% of predicted at Screening.
11. FEV1/FVC ≥60%, or if FEV1/FVC <60% then FEV1 must be ≥60% of predicted at Screening.
12. For patients enrolled or planned to be enrolled in a cardio-pulmonary rehabilitation program based on exercise training, one of the following must apply:
• In the maintenance phase of the program at the time of randomization with no plans to stop the program until Week 39, or
• Start of the cardio-pulmonary rehabilitation program based on exercise training is planned after Week 39.
13. A woman must be
a. Not of childbearing potential
b. Of childbearing potential and
o Have a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) at Screening and a negative urine pregnancy test at randomization.
o Agree to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study intervention discontinuation.
o Practicing an acceptable method of contraception and agree to remain on an acceptable method while receiving study intervention and until 30 days after last dose of study intervention. Examples of acceptable methods of contraception are located in Appendix 5.
14. A woman using oral contraceptives must have been using this method for at least 1 month prior to randomization.
15. Willing and able to adhere to the lifestyle restrictions specified in Section 5.3.

E.4

Principal exclusion criteria

1. PH due to left heart disease (PAWP >15 mmHg).
2. PH due to compression of pulmonary arteries and/or pulmonary veins.
3. History of left heart failure (LHF) as assessed by the investigator including cardiomyopathies and cardiac sarcoidosis, with a left ventricular ejection fraction (LVEF) <40%.
4. Severe coronary heart disease (CHD) or unstable angina as assessed by the investigator.
5. Myocardial infarction within the last 6 months prior to or during Screening.
6. Criterion modified per Amendment 2.
6.1 Decompensated cardiac failure not receiving optimal medical treatment according to local guidelines.
7. Arrhythmias assessed as severe by the investigator.
8. Criterion modified per Amendment 2.
8.1 Implantable cardioverter defibrillator (ICD) for secondary prevention (current or planned).
9. Cerebrovascular events (eg, transient ischemic attack, stroke) within the last 90 days prior to or during Screening.
10. Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to PH.
11. Overt features of pulmonary veno-occlusive disease (PVOD).
12. Significant emphysema as assessed by the investigator.
13. Criterion modified per Amendment 2.
13.1 Known and documented severe hepatic impairment (eg. Child-Pugh Class C). Note: the assessment of hepatic impairment (Child-Pugh Score) must be fully documented for patients who have clinical signs and evidence (from central and/or local lab) of hepatic impairment.
14. Severe renal failure (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 or serum creatinine >2.5 mg/dL) based on central laboratory results from the Screening blood sample.
15. Criterion modified per Amendment 2.
15.1 Treatment with prostacyclin, prostacyclin analogues or IP receptor agonists (ie, selexipag) within 90 days prior to randomization and/or prior to the RHC qualifying for enrollment, except those given at vasodilator testing during RHC.
16. Included on a lung transplant list or planned to be included until Visit 6 / Week 39.
17. Known or suspected uncontrolled thyroid disease as per investigator judgment.
18. Treatment with moderate inducers of CYP2C8, eg rifampicin or strong inhibitors of CYP2C8, eg, gemfibrozil at or within 14 days prior to randomization.
19. Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to RHC qualifying for enrollment.
20. SBP <90 mmHg at Screening or at randomization.
21. Known allergies, hypersensitivity, or intolerance to selexipag or its excipients (refer to Investigator’s Brochure).
22. Planned or current treatment with another investigational treatment up to 90 days prior to randomization.
23. Received an investigational intervention or used an invasive investigational medical device within 90 days prior to randomization.
24. Any condition for which, in the opinion of the investigator, participation would not be in the best interests of the participant (eg, compromise well-being), or that could prevent, limit, or confound the protocol-specified assessments.
25. Any acute or chronic impairment that may influence the ability to comply with study requirements such as to perform RHC, a reliable and reproducible 6MWT (eg, use of walking aids (cane, walker, etc.), or lung function tests.
26. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
27. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study of within 30 days after the last dose of study intervention.

E.5 End points

E.5.1

Primary end point(s)

• PVR on study intervention up to Week 26 expressed as percent of the baseline value.

E.5.1.1

Timepoint(s) of evaluation of this end point

2 to 5 hours post-dose at week 26

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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

E.6.7

Pharmacodynamic

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

Yes

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

Belgium

Brazil

Canada

Czechia

France

Germany

Italy

Netherlands

Spain

United Kingdom

United States

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

LVLS

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:

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

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)

After the participant has completed or discontinued the study, the investigator/delegate will explain what treatment(s) / medical care is necessary and available according to local regulations. If indicated, the sponsor will provide participants who completed the study and did not prematurely discontinue study intervention with selexipag until access to commercial selexipag is possible in this indication in the participant’s country of residence, according to local regulatory requirements.

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

2019-07-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-14

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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