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

• Register: EUCTR
• Last refreshed on: 22 October 2018
• Main ID: EUCTR2013-001492-20-PT
• Date of registration: 24/01/2014
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 05/03/2014
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001492-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Ireland, Portugal, Spain, United Kingdom

Contacts

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Rheumatoid arthritis
MedDRA version: 16.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Code: 0109-0012A 100 mg/ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
Other descriptive name: NNC0109-0012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 95-140
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Humira
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to Week 12

Primary end point(s): Change in the total histopathological synovitis score.

Main Objective: 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

Secondary Objective: • 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

Secondary Outcome(s)

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

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

Secondary ID(s)

2013-001492-20-IE

NN8226-4064

Source(s) of Monetary Support

Novo Nordisk A/S