Clinical Trials Register

Summary
EudraCT Number:	2015-002586-39
Sponsor's Protocol Code Number:	MC-TER.2/SSc
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-07-06
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

Portugal - INFARMED

A.2

EudraCT number

2015-002586-39

A.3

Full title of the trial

Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial to
Evaluate the Efficacy and Safety of Terguride Plus Symptomatic Therapy
in Subjects With Diffuse Cutaneous Systemic Sclerosis

A.3.1

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

Terguride Plus Symptomatic Therapy in Patients with Diffuse Cutaneous Systemic Sclerosis

A.3.2

Name or abbreviated title of the trial where available

TERGISS

A.4.1

Sponsor's protocol code number

MC-TER.2/SSc

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	medac GmbH
B.1.3.4	Country	Germany
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	medac GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	medac GmbH
B.5.2	Functional name of contact point	Project Manager Clinical Research
B.5.3	Address:
B.5.3.1	Street Address	Theaterstrasse 6
B.5.3.2	Town/ city	Wedel
B.5.3.3	Post code	D 22880
B.5.3.4	Country	Germany
B.5.4	Telephone number	494103 8006 434
B.5.5	Fax number	494103 8006 422
B.5.6	E-mail	c.guimbal-schmolck@medac.de

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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/153/12
D.3 Description of the IMP
D.3.1	Product name	Terguride
D.3.4	Pharmaceutical form	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	TERGURIDE HYDROGENMALEATE
D.3.9.1	CAS number	37686-85-4
D.3.9.4	EV Substance Code	SUB04725MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
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	Yes
D.3.11.13.1	Other medicinal product type	Semisynthetic ergot alkaloide, which was developed as dopaminergic agent and approved as drug for various indications
D.IMP: 2
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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/153/12
D.3 Description of the IMP
D.3.1	Product name	Terguride
D.3.4	Pharmaceutical form	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	TERGURIDE HYDROGENMALEATE
D.3.9.1	CAS number	37686-85-4
D.3.9.4	EV Substance Code	SUB04725MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Yes
D.3.11.13.1	Other medicinal product type	Semisynthetic ergot alkaloide, which was developed as dopaminergic agent and approved as drug for various indications

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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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

Diffuse cutaneous systemic sclerosis (dcSSc)

E.1.1.1

Medical condition in easily understood language

systemic sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10042953
E.1.2	Term	Systemic sclerosis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

The primary objective is to assess the efficacy of terguride compared to placebo in terms of absolute change in the mRSS during the double-blind treatment phase in subjects with dcSSc.

E.2.2

Secondary objectives of the trial

The secondary and other objectives include the following:
• To assess the efficacy of terguride compared to placebo in terms of impact on skin thickening, visceral involvement, functional status, quality of life, and pharmacodynamic parameters during the double-blind treatment phase.
• To assess the safety of terguride compared to placebo in a 52-week double-blind treatment phase.
• To assess the efficacy and safety of terguride in the open-label, 52-week open-label extension phase.
• To assess the prognostic value of CYP2D6 polymorphism with regard to the HIwT terguride dosage.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each subject must meet all of the following criteria to be enrolled in this study (criterion #7 must also be met for inclusion in the open-label extension phase of the study):
1. Is a male or female ≥18 years of age.
2. Fulfills the ACR/EULAR 2013 criteria for classification of SSc
3. Has diffuse cutaneous involvement (defined by skin fibrosis in at least 1 of the following sites: upper arms, thorax, abdomen, or thighs) according to scleroderma classification criteria (LeRoy et al 1988), confirmed independently by a second investigator who is unaware of the assessment of the first investigator.
4. Has a baseline mRSS between 10 and 25 units, inclusive.
5. Has had onset of the first non-Raynaud’s manifestation of SSc within 36 months of screening.
6. Is willing and able to comply with all aspects of the study; in particular, has the ability to attend study visits and assessments at least until the end of the double-blind treatment phase.
7. If a male subject is capable of reproduction or a female subject is of childbearing potential, he/she consents to practice sexual abstinence (Sexual abstinence refers to refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.) or use another highly effective method of contraception (Pearl index < 1), such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system, bilateral tubal occlusion or vasectomy in combination with a second method of contraception, such as a condom or a cervical cap/diaphragm with spermicide, during the trial and for at least 6 months thereafter.
8. Has provided written informed consent.

E.4

Principal exclusion criteria

Subjects meeting any of the following criteria will be excluded from the study:
1. Has abnormal hematological values prior to baseline (Visit 2).
2. Has abnormal liver function tests prior to baseline (Visit 2).
3. Has abnormal renal function tests prior to baseline (Visit 2).
4. Has any known renal crisis history.
5. Has cardiac abnormalities at screening (Visit 1).
6. Has any of the following lung criteria at screening (Visit 1):
• Forced vital capacity (FVC) <40% predicted
• Diffusing capacity of the lung for carbon monoxide (DLCO) <30% predicted.
7. Has a previous diagnosis of severe pulmonary arterial hypertension (PAH).
8. Has malabsorption requiring parenteral nutrition at screening (Visit 1).
9. Has had treatment with putative disease-modifying agents within 8 weeks of screening.
10. Has had treatment with cyclophosphamide within 26 weeks of screening (Visit 1).
11. Has had treatment with rituximab within 52 weeks of screening (Visit 1).
12. Has a known acute or uncontrolled chronic infection (eg, hepatitis B or C, tuberculosis, or human immunodeficiency virus [HIV]).
13. History of hematopoietic stem cell transplantation or planned hematopoietic stem cell transplantation within the next 12 months, or total lymphoid irradiation.
14. Has any concurrent medical condition(s) that, in the opinion of the investigator, may confound the results of the study.
15. Is pregnant or lactating.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the absolute change in mRSS between baseline and Week 52 of the double-blind treatment phase.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52 of double blind phase

E.5.2

Secondary end point(s)

• The absolute change in total score of the HAQ-DI between baseline and Week 52 of the double-blind treatment phase.
• The binary mRSS response defined as improvement of mRSS by at least 30% (relative) or 5 points (absolute) between baseline and Week 52 of the double-blind treatment phase.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 52 of double blind phase

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

Yes

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of life

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

France

Germany

Hungary

Italy

Netherlands

Poland

Portugal

Romania

Switzerland

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

The end of the study is defined as the date on which all subjects have completed, or have had the opportunity to complete, the safety visit (Visit 13).

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:

134

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

100

F.4.2.2

In the whole clinical trial

148

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)

Patient’s care after end of trial participation will be left at the doctor’s discretion. Subjects who would like to remain on protocol-specified therapy after the open-label extension phase has been completed will be permitted to continue treatment at the investigator’s discretion, as provided for by the local country’s regulatory mechanisms. Data collection during this phase will be limited to administration of protocol-specified therapy and SAE reporting.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-03

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2018-06-05

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