Clinical Trials Register

Summary
EudraCT Number:	2019-002036-90
Sponsor's Protocol Code Number:	Uni-Koeln-3815
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-10-02
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

Germany - PEI

A.2

EudraCT number

2019-002036-90

A.3

Full title of the trial

A randomized, placebo-controlled phase IIa clinical trial to evaluate the efficacy and safety of subcutaneous Dupilumab in localized scleroderma

Randomisierte, Placebo kontrollierte klinische Phase IIa Studie zur Bewertung der Wirksamkeit und Sicherheit von subkutanem Dupilumab bei zirkumskripter Sklerodermie

A.3.1

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

Study to test effectiveness and safety of the drug Dupilumab in patients with localized scleroderma

Studie zur Bewertung der Wirksamkeit und Sicherheit des Medikaments Dupilumab bei Patienten mit zirkumskripter Sklerodermie

A.3.2

Name or abbreviated title of the trial where available

DupiMorph

A.4.1

Sponsor's protocol code number

Uni-Koeln-3815

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04200755

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	University of Cologne
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi Aventis
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	CTC Cologne
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Gleueler Str. 269
B.5.3.2	Town/ city	Cologne
B.5.3.3	Post code	50935
B.5.3.4	Country	Germany
B.5.4	Telephone number	004922147888793
B.5.5	Fax number	004922147888209
B.5.6	E-mail	sabine.schleicher1@uk-koeln.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dupilumab
D.3.2	Product code	Dupilumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	Dupilumab
D.3.9.1	CAS number	1190264-60-8
D.3.9.3	Other descriptive name	SAR231893
D.3.9.4	EV Substance Code	SUB88511
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	150
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	Yes
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	Solution for injection in pre-filled syringe
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

Localized scleroderma

Zirkumskripte Sklerodermie

E.1.1.1

Medical condition in easily understood language

Localized scleroderma

Zirkumskripte Sklerodermie

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10009206
E.1.2	Term	Circumscribed scleroderma
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10018124
E.1.2	Term	Generalized scleroderma
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10027979
E.1.2	Term	Morphea
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate, in comparison with placebo, the efficacy of Dupilumab in patients with Morphea (plaque type) or Generalized localized scleroderma (affecting at least three anatomic sites).

E.2.2

Secondary objectives of the trial

• To evaluate, in comparison with placebo, the effect of Dupilumab on:
o Disease activity/skin damage score (mLoSSI/LoSDI) during treatment phase
o Disease activity/skin damage score (mLoSSI/LoSDI) after end of treatment until 24 weeks after end of treatment
o Disease activity/skin damage score (mLoSSI/LoSDI) of other existing (non-target) lesions and new lesions
o The potential for an attenuated gene signature of localized scleroderma (RNA-seq, RT-qPCR)
o The potential for an attenuated histology (quantity and quality of cellular composition, extracellular matrix composition, altered skin architecture)
o On the quality of life of patients (DLQI questionnaire)
• To evaluate the safety profile of Dupilumab (AEs, physical examination, vital signs, clinical laboratory evaluations including hematology, biochemistry and urine analysis)
• To evaluate immunogenicity of Dupilumab treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is a male or female ≥18 years of age on the day the study informed consent is signed
2. Out-patient status
3. Caucasian, whereby the term comprises people with a light skin type that does not interfere with the evaluation (Fitzpatrick type I-V)
4. Morphea (plaque type) or Generalized localized scleroderma (affecting at least three anatomic sites)
5. At least one lesions with lilac ring (active phase of the disease);
6. Activity of LS within the last 12 month (as defined by progression of size or new developing plaque)
7. For women of childbearing potential: negative pregnancy test at Visit 1
8. For women of childbearing potetnial: Use of effective method of contraceptionfrom 4 weeks prior to enrolment, throughout the study treatment until 12 weeks after the last IMP dose
9. Written informed consent signed

E.4

Principal exclusion criteria

1. Systemic immunosuppressive therapy or UV therapy in doses relevant for the treatment of Morphea (plaque type) less than 3 months before enrolment.
2. Participation in another trial of IMPs or devices parallel to, or less than 6 months before or previous participation in this trial
3. Pregnancy or breastfeeding mother
4. Diagnosis of other significant chronic inflammatory or autoimmune disorders.
5. Topical immunosuppressive therapy less than 1 month before enrollment
6. Concurrent phototherapy
7. Known infection with helminths (helminthose)
8. Any condition or laboratory abnormality that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study. E.g. uncontrolled psychiatric illness or history of clinical relevant drug abuse.
9. Known hypersensitivity to any components of the IMP
10. Treatment with a live (attenuated) vaccine within 3 months prior to enrollment
11. Histroy of malignancy (except patients with complteels reated in situ carcinoma of the cervix, completely treated and resolved non-metastatic suamous or basal cell carcinoma or the skin).
12. Known diagnosis of active tuberculosis or non-tuberculous mycobacterial infections or latens untreated tuberculosis unless it is well documented by a specialist that the patient has been adequately treated.
13. Known diagnosis of HIV, HBV or HCV infection
14. Reguklar use (more than 2 visits per week) or a tanning booth/parlor
15. Known diagnosis of asthma including allergic asthma, with pathological lung function test and requirement of daily pharmaceutical treatment at the time of inclusion.

E.5 End points

E.5.1

Primary end point(s)

To determine the efficacy of Dupilumab treatment response of patients with LS will be assessed by multiple measures which have been developed and validated in previous clinical trials and which are used within the ENLS (European Network for Localized Scleroderma) for the assessment of patients with LS (7). Personnel involved in data acquisition during the trial will be specifically trained in the assessment procedures.
At baseline visit (V1) a single existing lesion with the highest mLoSSI activity index will be defined as target lesion.
Treatment response is determined by change in mLoSSI (size of lesion, erythema, skin thickening) or LoSDI (dermal athrophy, subcutaneous atrophy, dyspigmentation) of the target lesion; score reduction by 50% after 24 weeks (EoT V14) compared to baseline (V1) is defined as treatment response.

E.5.1.1

Timepoint(s) of evaluation of this end point

EoT V14

E.5.2

Secondary end point(s)

• mLoSSI of target lesion during treatment and during follow-up
• LoSDI (dermal athrophy, subcutaneous atrophy, dyspigmentation) of target lesion during treatment, at EoT and during follow-up
• Count of all existing non-target and new lesions on the entire integument during treatment, at EoT and during follow-up
• mLoSSI and LoSDI of all existing non-target lesions and new lesions on the entire integument during treatment, at EoT and during follow-up
• Gene signature of localized scleroderma after Dupilumab treatment: RNA-seq, RT-qPCR of tissue biopsies obtained from the lesion (lilac ring, optional: center) and healthy skin before (baseline visit V1) and after treatment (EoT V14)
• Histology of localized scleroderma after Dupilumab treatment: tissue biopsies obtained from the lesion (lilac ring, optional: center) and healthy skin before (baseline visit/V1) and after treatment (EoT V14). Analysis of quantity and quality of cellular composition, extracellular matrix composition, altered skin architecture)
• DermatoLogy Quality of life Index (DLQI)
• Safety profile of Dupilumab:
- Adverse events (AEs)/treatment-emergent adverse events (TEAEs)
- Physical examination and body weight
- Vital signs
- Clinical laboratory evaluations including hematology, biochemistry
• Anti-drug antibody levels (optional)
• Anti-nuclear antibodies (ANAs) levels
• Serum cytokine levels

E.5.2.1

Timepoint(s) of evaluation of this end point

EoT V14 and/or FU visits V15 and V16

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

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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.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 end of IMP treatment the subject will be treated according to local standard of care. No additional care due to trial participation is expected to be required.

Nach Abschluss der IMP-Behandlung wird der Patient nach dem lokalen Standard behandelt. Es wird erwartet, dass keine zusätzliche Behandlung aufgrund der Teilnahme an der Studie erforderlich ist.

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

2019-12-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-11-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-11-30

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