Clinical Trials Register

Summary
EudraCT Number:	2013-001492-20
Sponsor's Protocol Code Number:	NN8226-4064
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-10-18
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

UK - MHRA

A.2

EudraCT number

2013-001492-20

A.3

Full title of the trial

A randomised, active comparator, double-blind, multi centre, parallel, phase 2a trial, investigating the mechanism of action of NNC0109-0012 (anti-IL-20 mAb) through synovial biopsies in subjects with rheumatoid arthritis and an inadequate response to Methotrexate

A.3.1

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

A trial investigating the mechanism of action of NNC0109-0012 (anti-IL-20 mAb) through synovial biopsies in subjects with rheumatoid arthritis and an inadequate response to Methotrexate

A.4.1

Sponsor's protocol code number

NN8226-4064

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1141-3512

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	Novo Nordisk A/S
B.1.3.4	Country	Denmark
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	Novo Nordisk A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novo Nordisk A/S
B.5.2	Functional name of contact point	Global Clinical Registry (GCR,1452)
B.5.3	Address:
B.5.3.1	Street Address	Vandtaarnsvej 114, VTB
B.5.3.2	Town/ city	Soeborg
B.5.3.3	Post code	DK-2860
B.5.3.4	Country	Denmark
B.5.6	E-mail	clinicaltrials@novonordisk.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.3.2	Product code	0109-0012A 100 mg/ml
D.3.4	Pharmaceutical form	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	N/A
D.3.9.3	Other descriptive name	NNC0109-0012
D.3.9.4	EV Substance Code	SUB30323
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	95 to 140
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Humira
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Ltd
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Yes
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.4	EV Substance Code	SUB20016
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	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
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

Rheumatoid arthritis

E.1.1.1

Medical condition in easily understood language

RA, Rheumatoid arthritis, autoimmune disease that causes chronic joint inflammation

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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

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 explore the potential differences in the mechanism of action through analysis of synovial biopsies in subjects with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) after 12 weeks of treatment with NNC0109-0012 and adalimumab

E.2.2

Secondary objectives of the trial

• To compare joint changes measured by magnetic resonance imaging (MRI) scans and ultrasound in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab
• To compare changes in disease activity in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab
• To describe the safety and tolerability of NNC0109-0012 and adalimumab in subjects with active RA and an inadequate response to MTX
• To compare changes in biomarkers in blood and synovial biopsies in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab
• To compare changes measured by MRI scans and ultrasound, disease activity, biomarkers in blood and the safety and tolerability in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab and additional 12 weeks of follow up

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female age ≥18 and ≤ 75 years at the time of signing informed consent.
2. A diagnosis of RA at least 6 months prior to screening visit, according to the American College of Rheumatology (EULAR/ACR 2010 criteria) or by standard criteria (ACR 1987) if diagnosis was made earlier than 2010.
3. Subjects with ACR global functional status of 1 to 3
4. Active RA, characterised by:
• DAS28 (CRP) > 4.5 and
• ≥ 6 tender and ≥ 6 swollen joints based on a 66/68 joint count
5. Active Synovitis in at least two joints of the wrist and metacarpophalangeal joints, as assessed by high frequency Power Doppler ultrasound scan at screening and randomisation

E.4

Principal exclusion criteria

1. Subjects with arthritis due to other autoimmune diseases than RA
2. Body weight > 90.0 kg
3. History of or current inflammatory joint disease other than RA (e.g. gout, psoriatic or reactive arthritis, Lyme disease, juvenile idiopathic arthritis, excluding secondary Sjogren syndrome and hypothyroidism)
4. Any active or on-going bacterial infections within 4 weeks prior to screening visit, unless treated and resolved with appropriate therapy or any history of recurrent infections or conditions predisposing to chronic infections (e.g., bronchiectasis, chronic osteomyelitis)
5. Subjects with malignancy within the previous 5 years with the exception of adequately treated and cured basal or squamous cell carcinoma of the skin or cervical carcinoma in situ occurring more than 12 months prior to screening visit
6. Female who is pregnant, breast feeding, intends to become pregnant or is of childbearing potential, not willing to use two highly effective contraceptive methods (adequate highly effective contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system) one of which has to be a barrier method a barrier method of contraception (e.g. condom with spermicidal foam/gel/film/cream), for at least 16 weeks (approximately 5 half-lives) following the last dose of trial medication
7. Male subjects who are sexually active and not surgically sterilised, who or whose partner are unwilling to use two different forms of highly effective contraception, one of which has to be a barrier method a barrier method of contraception (e.g. condom with spermicidal foam/gel/film/cream) for the duration of the trial and for at least 16 weeks (approximately 5 half-lives) following the last dose of trial medication

E.5 End points

E.5.1

Primary end point(s)

Change in the total histopathological synovitis score.

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to Week 12

E.5.2

Secondary end point(s)

Efficacy endpoints
• Change in dynamic contrast enhanced MRI (DCE-MRI) measures of initial rate of enhancement (IRE)
• Change in dynamic contrast enhanced MRI (DCE-MRI) measures of maximal enhancement (ME)
• Changes in RA-MRI scores (RAMRIS) of synovitis
• Changes in RA-MRI scores (RAMRIS) of oedema
• Changes in RA-MRI scores (RAMRIS) of erosion
• Change in high frequency ultrasound with Power Doppler measures of total synovitis
• Change in high frequency ultrasound with Power Doppler measures of total tenosynovitis scores
• Change in disease activity 28 – C-reactive protein (DAS28 (CRP)

Safety and tolerability endpoints
1• Incidence of Adverse Events (AE)
2• Incidence of local intolerability at the injection site

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy endpoints
• From baseline to Week 12

Safety and tolerability endpoints
1• From baseline to Week 24
2• From baseline until 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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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)

Yes

E.8.2.2

Placebo

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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)

N/A

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

2013-11-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-08-11

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