A trial of NNC0109-0012, an anti-IL-20 biologic, in patients with active rheumatoid arthritis who are inadequate responders to Methotrexate

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2012-000610-11-ES
• Date of registration: 09/07/2012
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A trial of NNC0109-0012, an anti-IL-20 biologic, in patients with active rheumatoid arthritis who are inadequate responders to Methotrexate
• Scientific title: A randomised, double blind, placebo-controlled, multiple dose, phase 2b, 24 week trial followed by an open label extension of NNC0109-0012, an anti-IL-20 biologic, in patients with active rheumatoid arthritis who are inadequate responders to Methotrexate
• Date of first enrolment: 17/10/2012
• Target sample size: 268
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000610-11
• 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: yes Other trial design description: Followed by an open label extension period If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Argentina, Belgium, Brazil, Canada, Czech Republic, European Union, Germany, Hungary, Italy, Mexico, Russian Federation, Spain, Ukraine, United States

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. Informed consent must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
2. Age between 18 and 75 years (both years inclusive)
3. A documented 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.
4. Active RA, characterised by:
a. > 5 tender and > 5 swollen joints based on a 28 joint count
b. CRP ? 1.0 mg/dL (10 mg/L)
5. Patients can be on methotrexate with or without hydroxychloroquine/chloroquine
a. Methotrexate treatment (? 15.0 mg/week) for at least 16 weeks, (? 15.0 mg/week to ? 25 mg/week) for at least 8 weeks prior to screening. Patient can be on MTX as low as 10 mg/week only if due to MTX intolerance
b. Hydroxychloroquine (200-400 mg/day p.o.) or chloroquine (250-500 mg/day p.o.) treatment for at least 8 weeks prior to screening visit
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 238
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1. Patients with arthritis due to other autoimmune diseases than RA
2. Any active or ongoing 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)
3. History of severe, systemic viral or fungal infections within the past 6 months prior to screening visit, unless treated and/or resolved with appropriate therapy
4. Patients with active 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
5. Females of childbearing potential who are pregnant or breast feeding or intend to become pregnant
6. Any other disease or clinically significant abnormality in laboratory parameters which, according to the Investigator, might compromise the safety of the patient, interfere with participation in the trial or compromise the trial objective


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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Code: 0109-0012A 100 mg/ml
Pharmaceutical Form: Solution for injection
Current Sponsor code: NNC0109-0012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Code: 0109-0012A 50 mg/ml
Pharmaceutical Form: Solution for injection
Current Sponsor code: NNC0109-0012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Code: 0109-0012A 25 mg/ml
Pharmaceutical Form: Solution for injection
Current Sponsor code: NNC0109-0012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: - To investigate the effects of NNC0109-0012 compared to placebo on additional clinical outcomes measuring disease activity
- To investigate the effects of NNC0109-0012 compared to placebo on Patient Reported Outcomes (PROs)
- To investigate the effects of NNC0109-0012 compared to placebo on biomarkers assessing disease activity, MoA, structural damage in addition to total IL-20 and biomarkers predictive of response
- To describe safety and tolerability of NNC0109-0012
- To describe the trough concentration of NNC0109-0012 at steady state
- To describe the potential immunogenicity of NNC0109-0012
- To explore the dose response relationship for NNC0109-0012 on clinical efficacy outcomes
- To investigate the effect of NNC0109-0012 compared to placebo on health care resource utilisation

Primary end point(s): ACR20 (defined as 20% improvement in American College of Rheumatology criteria measures) (i.e., responder or non-responder)

Main Objective: To investigate the clinical efficacy of NNC0109-0012 compared to placebo when administered as weekly repeat s.c. injections in patients with active rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX) while on a stable background of MTX therapy.

Timepoint(s) of evaluation of this end point: At Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: All key secondary endpoints will be determined at Weeks 12 and 24.
Key secondary endpoints during the open label extension (week 52) will be safety and ACR20/50/70.

Secondary end point(s): 1- ACR20, ACR50 and ACR70
2- Change in DAS28-CRP (defined as Disease Activity Score for 28 joints with C-reactive protein measure) from baseline
3- Simplified Disease Activity Index (SDAI) remission (SDAI of 3.3 or below)
4- European League Against Rheumatism (EULAR) criteria response
5- Change from baseline in the overall scores of the following PRO measures:
- Health Assessment Questionnaire ? Disability Index (HAQ-DI)
- Short Form Health Survey (SF-36v2)
6- Safety endpoint :
- Incidence and type of adverse events (AEs)
7- Radiographic assessments
- Change from baseline in van der Heijde sharp score

Secondary ID(s)

2012-000610-11-BE

NN8226-3613

Source(s) of Monetary Support

Novo Nordisk A/S