A Trial of NNC0109-0012, an Anti-IL-20 Biologic, in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to Methotrexate

Study Overview
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Brief Summary
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This trial is conducted in Europe, North America and South America. The aim of this trial is to investigate the clinical efficacy of NNC0109-0012, a human monoclonal antibody, compared to placebo when administered as weekly repeat subcutaneous (under the skin) injections in to patients with active rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX) while on a stable background of MTX therapy.

Official Title
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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

Conditions
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Inflammation, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: NNC0109-0012
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - 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 - 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 - Active RA, characterised by: a. more than 5 tender and more than 5 swollen joints based on a 28 joint count b. C-reactive protein (CRP) above or equal to 1.0 mg/dL (10 mg/L) - Patients can be on methotrexate with or without hydroxychloroquine/chloroquine: a. Methotrexate treatment (above or equal to 15.0 mg/week) for at least 16 weeks, (above or equal to 15.0 mg/week to below or equal 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 per os, oral dosing (p.o.)) or chloroquine (250-500 mg/day p.o.) treatment for at least 8 weeks prior to screening visit Exclusion Criteria: - Patients with arthritis due to other autoimmune diseases than RA - 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) - 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 - 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 - Females of childbearing potential who are pregnant or breast feeding or intend to become pregnant - 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 60 mg<br> | Drug: NNC0109-0012<br>* Administered subcutaneously (s.c., under the skin), once weekly.<br>|
| Experimental: 120 mg<br> | Drug: NNC0109-0012<br>* Administered subcutaneously (s.c., under the skin), once weekly.<br>|
| Experimental: 240 mg<br> | Drug: NNC0109-0012<br>* Administered subcutaneously (s.c., under the skin), once weekly.<br>|
| Experimental: Placebo<br> | Drug: placebo<br>* Administered subcutaneously (s.c., under the skin), once weekly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 (defined as 20% improvement in American College of Rheumatology criteria measures) |  | At week 12 (responder or non-responder) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20, ACR50 and ACR70 improvement of ACR score from baseline |  | At weeks 12 and 24 | 
| Change in DAS28-CRP (defined as Disease Activity Score for 28 joints with C-reactive protein measure) from baseline |  | At weeks 12 and 24 | 
| Simplified Disease Activity Index (SDAI) remission (SDAI of 3.3 or below) |  | At weeks 12 and 24 | 
| European League Against Rheumatism (EULAR) criteria response |  | At weeks 12 and 24 | 
| Change from baseline in the overall scores of Short Form Health Survey (SF-36v2) |  | At weeks 12 and 24 | 
| Change from baseline in the overall scores of Health Assessment Questionnaire - Disability Index (HAQ-DI) |  | At weeks 12 and 24 | 
| Incidence and type of adverse events (AEs) |  | At weeks 12 and 24 | 
| Change from baseline in van der Heijde modified Sharp score |  | At weeks 12 and 24 | 
| ACR20/50/70 (20%, 50% or 70% improvement of ACR (American College of Rheumatology) score from baseline) |  | Week 52 | 
| Incidence and type of adverse events (AEs) |  | Week 52 |