A Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NNC0215-0384 Administered to Subjects With Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of the trial is to investigate the safety, tolerability, pharmacokinetics (exposure of the trial drug in the body) and pharmacodynamics (the effect of the investigated drug on the body) of NNC0215-0384 administered to subjects with moderate to severe rheumatoid arthritis (RA) concomitantly treated with methotrexate (MTX).

Official Title
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A Randomised, Placebo-controlled, Double-blind Within Cohort, Dose Escalation, Multiple-dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NNC0215-0384 Administered Subcutaneously to Subjects With Moderate to Severe Rheumatoid Arthritis

Conditions
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Inflammation, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: NNC0215-0384
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age between 18 and 75 years (both years inclusive), for Russia only: Age between 18-65 years (both years inclusive) Moderate to severe RA, confirmed by a Disease Activity Score based on 28 joints and C-reactive protein (DAS28 (CRP)) equal to or above 4.5 and a minimum of five tender and five swollen joints based on a 28 joint count (a joint can score as both tender and swollen) MTX (10-25 mg/week both inclusive) for at least 16 weeks, with an unchanged dose for at least 6 weeks prior to screening and until randomisation Females who are not of child-bearing potential must have been post-menopausal for at least 1 year confirmed by follicle-stimulating hormone (FSH) equal to or above 26.7 U/L or be surgically sterile Exclusion Criteria: Past or current inflammatory joint disease other than RA (e.g. gout [crystal proven], psoriatic arthritis, juvenile idiopathic arthritis, reactive arthritis or Lyme disease Any active or ongoing chronic infectious disease (e.g. chronic osteomyelitis, chronic pyelonephritis) within 4 weeks prior to randomisation Clinically significant cardiac or cardiovascular disease Past or current malignancy Evaluation of tuberculosis screening indicative of latent or active tuberculosis (TB)

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: Dose level 1<br> | Drug: NNC0215-0384<br>* A total of seven once-weekly doses of NNC0215-0384 or placebo will be administered subcutaneously (s.c., under the skin) at one of three ascending dose levels. Each cohort will consist of eight subjects randomised to either active (6 subjects) or placebo (2 subjects) treatment. Each subject will participate in one cohort only. Dose-escalation to the next dose level will be initiated when the safety data has been evaluated and if considered safe.<br>Drug: placebo<br>* Placebo administered corresponding to NNC0215-0384 treatment<br>|
| Experimental: Dose level 2<br> | Drug: NNC0215-0384<br>* A total of seven once-weekly doses of NNC0215-0384 or placebo will be administered subcutaneously (s.c., under the skin) at one of three ascending dose levels. Each cohort will consist of eight subjects randomised to either active (6 subjects) or placebo (2 subjects) treatment. Each subject will participate in one cohort only. Dose-escalation to the next dose level will be initiated when the safety data has been evaluated and if considered safe.<br>Drug: placebo<br>* Placebo administered corresponding to NNC0215-0384 treatment<br>|
| Experimental: Dose level 3<br> | Drug: NNC0215-0384<br>* A total of seven once-weekly doses of NNC0215-0384 or placebo will be administered subcutaneously (s.c., under the skin) at one of three ascending dose levels. Each cohort will consist of eight subjects randomised to either active (6 subjects) or placebo (2 subjects) treatment. Each subject will participate in one cohort only. Dose-escalation to the next dose level will be initiated when the safety data has been evaluated and if considered safe.<br>Drug: placebo<br>* Placebo administered corresponding to NNC0215-0384 treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | From first dosing until 19 weeks after first dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of NNC0215-0384 in serum |  | 7 days after each dose | 
| Concentration of NNC0215-0384 in serum |  | 3 days after first and last dose | 
| Duration of full and duration of detectable levels of C5a receptor (C5aR) occupancy by NNC0215-0384 on neutrophils from baseline |  | From week 0 until 19 weeks after first dosing | 
| Change in health assessment questionnaire - disability index (HAQ-DI) from baseline |  | Week 0, week 7 first dosing | 
| Incidence and characterisation of antibodies directed against NNC0215-0384 and, if present, their in vitro neutralising activity |  | From first dosing until 19 weeks after first dosing |