Clinical Trials Register

Summary
EudraCT Number:	2013-002470-46
Sponsor's Protocol Code Number:	CIM003JG
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:	2013-09-27
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

2013-002470-46

A.3

Full title of the trial

A Phase II, randomized, double-blind, placebo-controlled, multiple-dose study to evaluate the safety, tolerability, and efficacy of CIM331 in atopic dermatitis patients who are inadequately controlled by or intolerant to topical therapy

A.3.1

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

A Phase II repeated dose, randomized and blinded trial of CIM331 in patients with eczema in whom products applied to the skin do not provide sufficient relief or produce side effects

A.4.1

Sponsor's protocol code number

CIM003JG

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	Chugai Pharmaceutical Co. Ltd
B.1.3.4	Country	Japan
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	Chugai Pharmaceutical Co. Ltd
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Chugai Pharma Europe Ltd
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Mulliner House, Flanders Road
B.5.3.2	Town/ city	London
B.5.3.3	Post code	W4 1NN
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	442089875600
B.5.5	Fax number	442089875616
B.5.6	E-mail	regulatory@chugai-pharm.co.uk

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	CIM331
D.3.2	Product code	CIM331
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	Humanised monoclonal antibody IgG2 recognising the interleukin-31 receptor A
D.3.9.2	Current sponsor code	CIM331
D.3.9.3	Other descriptive name	humanised monoclonal antibody IgG2 recognising the interleukin-31 receptor A
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	100
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	Lyophilisate for solution 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

Atopic dermatitis

E.1.1.1

Medical condition in easily understood language

Eczema

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1) To evaluate the dose response profile of CIM331 in the treatment of pruritus as defined by the percent improvement in pruritus from baseline to Week 12, assessed by patients using the pruritus VAS (Part A).

E.2.2

Secondary objectives of the trial

1) To further evaluate the efficacy of CIM331 compared with placebo as measured by the EASI, SCORAD, sIGA, BSA of AD involvement, pruritus VAS, pruritus VRS, sleep disturbance VAS, time to rescue therapy, and proportion of patients receiving rescue therapy.
2) To evaluate the long-term efficacy profile of CIM331 (Part B).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria – Part A
Patients must meet the following criteria for study entry:
1. ≥18 and ≤65 years of age at the time of consent.
2. Patients must be able to give written informed consent and comply with the requirements of the study protocol.
3. Patients must satisfy the diagnostic criteria for AD as determined by the criteria of Hanifin and Rajka.
4. Patients must meet either a or b and c, d at the screening visit (Day -28 to Day -8):
a.Patients must have a history of inadequate response (defined as sIGA score ≥3) to a stable regimen ≥4* consecutive weeks of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI).
Note: TCS must be “potent” or “very potent” according to the classification provided in.
*Note: A TCS which is restricted for use <4 weeks in duration (e.g. clobetasol propionate) should be applied to the maximum allowed consecutive treatment period which may be <4 consecutive weeks.
b. Patients must have a history of intolerance to, or inability to receive, standard topical therapy (e.g. contraindication). Intolerance is defined as discontinuation due to systemic side effects or allergy to TCS and/or TCI (except for steroid acne, steroid flushing, skin atrophy, hypertrichosis and bacterial ⁄ fungal ⁄ viral skin infections).
Note: criteria c and d should only be assessed in patients who meet criteria a or b:
c. EASI ≥10.
d. Pruritus VAS ≥50 mm.
5. Patients must meet the following criteria at randomization:
a. Pruritus VAS ≥50 mm (last 3 consecutive days of the run-in period).
b. EASI ≥10.
c. sIGA score ≥3.
6. Both male and female patients of childbearing potential must agree for the duration of the study and for a period of 120 days after administration of the last dose of study drug to the consistent and correct use of an acceptable method of birth control (i.e. methods of birth control which result in a low failure rate [<1% per year] when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or surgically sterilized partner).

Inclusion Criteria (Part B only)
1. Patients who have completed the treatment period for Part A.
2. Patients who are willing to participate in Part B and are able to give written informed consent and comply with the requirements of the study protocol.

E.4

Principal exclusion criteria

Exclusion Criteria (Part A and Part B)
Patients who meet any of the following criteria will be excluded from study entry:
1. Known significant cardiac disease (New York Heart Association Class III or IV).
2. Any diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding, including aspartate aminotransferase or alanine aminotransferase >2 x upper limit of normal (ULN), or serum creatinine ≥2 mg/dL (177 µmol/L), or total white blood cells (WBC) <3000 cells/µL, or any other medical condition that, in the opinion of the Investigator, would contraindicate the use of an investigational drug.
3. Clinically significant electrocardiogram (ECG) abnormalities.
4. History of drug dependence or alcohol abuse.
5. Serological evidence of hepatitis B virus (hepatitis B surface antigen positive or hepatitis B core antibody positive) or hepatitis C virus (HCV) (anti-HCV antibody positive) infection (active or past infection). Testing prior to the study is mandatory.
6. Known human immunodeficiency virus (HIV) infection.
7. History of hypersensitivity, including anaphylaxis to an immunoglobulin product (plasma derived or recombinant, e.g. monoclonal antibody).
8. History of skin malignancy. Patients with a history of any other malignancy, who have been in remission for ≥5 years prior to randomization, or patients with a history of curatively treated in situ carcinoma of the cervix at any time prior to randomization, are eligible.
9. Active dermatological disease other than AD, which is being treated separately.
10. Eye disease requiring systemic treatment.
11. Ongoing treatment with specific or non-specific hyposensitization therapy for AD.
12. Treatment with systemic steroids, immunosuppressant agents or ultraviolet radiation therapy within 4 weeks prior to randomization.
13. Treatment with potent or very potent TCS within 2 weeks prior to randomization.
14. Treatment with mild or moderately potent TCS within 1 week prior to randomization.
15. Patients who have been receiving treatment for asthma within 1 year prior to randomization or who had previously been diagnosed with asthma and experienced asthmatic symptoms (including, but not limited to, wheezing, shortness of breath, cough after exercise) within 1 year prior to randomization.
16. Treated with TCI or vitamin D (including activated vitamin D) within 2 weeks prior to randomization.
17. Treated with an antihistamine (topical or systemic) within 1 week prior to randomization.
18. Treatment with a hypnotic within 1 week prior to randomization.
19. Treatment with any other therapy for AD and pruritus, including emollients (e.g. Atopiclair®, MimyX™) approved or cleared by FDA as devices, within 4 days prior to randomization.
20. History of infection including skin infection requiring treatment with oral or intravenous (IV) antibiotics, antivirals, or antifungals within 1 week prior to randomization.
21. Treatment with any investigational agent including placebo within 16 weeks prior to randomization.
22. <All countries except Germany>Evidence of tuberculosis (TB) infection as defined by a positive purified protein derivative (PPD) skin test and/or positive interferon-gamma release assay. Such patients may participate in the study if further diagnostic work-up according to local guidelines (including chest X-ray if appropriate) reveals no evidence of latent or active TB. The interferon-gamma release assay should be repeated in case of an indeterminate result.
<Germany only>Evidence of TB infection as defined by a positive PPD skin test and/or positive interferon-gamma release assay. The interferon-gamma release assay should be repeated in case of an indeterminate result.
23. Received a live vaccine within 4 weeks prior to randomization or plan to receive a live vaccine during the study.
24. Received a non-live vaccine (toxoid or killed infectious agent) within 1 week prior to randomization or plan to receive a non-live vaccine during the study.
25. Pregnant or lactating women.
26. Previous treatment with CIM331.

Exclusion Criteria (Part B only)
1. Patients who experienced a serious adverse event thought to be related to treatment with CIM331 in Part A.

E.5 End points

E.5.1

Primary end point(s)

Percent improvement from baseline in pruritus VAS at Week 12 (Part A).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12

E.5.2

Secondary end point(s)

Secondary efficacy outcome measures (Part A and Part B):
 Improvement from baseline in pruritus VAS, EASI, SCORAD, sIGA, Body Surface Area (BSA) of AD involvement, pruritus VRS and sleep disturbance VAS at Week 12 and selected time points.
 EASI: proportion of patients with 25%, 50%, 75% improvement from baseline at Week 12 and selected time points.
 SCORAD: proportion of patients with 25%, 50%, 75% improvement from baseline at Week 12 and selected time points.
 sIGA: Proportion of patients with a 2 or more point improvement from baseline at Week 12 and selected time points.
 Pruritus VAS: proportion of patients with 25%, 50%, 75% improvement from baseline at Week 12 and selected time points.
 Pruritus VRS: proportion of patients with a 2 or more point improvement from baseline at Week 12 and selected time points.
 Time to response of pruritus VAS improvement from baseline 25%, 50%, 75%.
 Time to response of EASI improvement from baseline 25%, 50%, 75%.
 Time to response of SCORAD improvement from baseline 25%, 50%, 75%.
 Time to response of 2 point improvement from baseline of sIGA.
 Time to rescue therapy.
 Proportion of patients receiving rescue therapy.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 12 and selected time points.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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

Germany

Japan

Poland

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:

250

F.1.3

Elderly (>=65 years)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

250

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

2014-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-03-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-06

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