First Human Dose Trial of NNC0215-0384 in Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to describe the safety and tolerability of single intravenous (i.v.) and subcutaneous (s.c.) doses of NNC0215-0384 in subjects with active rheumatoid arthritis (RA) on background methotrexate (MTX) treatment.

Official Title
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First Human Dose Trial of NNC0215-0384 in Subjects With Rheumatoid Arthritis

Conditions
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Inflammation, Rheumatoid Arthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active RA, characterised by a DAS28 (CRP)(Disease Activity Score based on 28 joints and CRP) above 3.2 and a minimum of two swollen joints based on a 68/66 joint count at screening Concomitant treatment with MTX (7.5 - 25 mg/week both inclusive) for at least 16 weeks, with a stable dose for at least 6 weeks prior to dosing Exclusion Criteria: Subjects with chronic inflammatory autoimmune disease other than RA History of or current inflammatory joint disease other than RA such as gout (crystal proven), psoriatic arthritis, juvenile idiopathic arthritis, current reactive arthritis or Lyme disease Any active or ongoing chronic infectious disease (e.g. chronic osteomyelitis, chronic pyelonephritis) requiring systemic anti-infectious treatment within 4 weeks prior to randomisation Clinically significant cardiac or cardiovascular disease Past or current malignancy Latent or active tuberculosis (TB) as documented by: A positive QuantiFeron® test (test can be performed up to 2 months prior to dosing). One retest is allowed in case of inconclusive results.- A history of active TB within the last 3 years even, if treated effectively. - A history of active TB more than 3 years ago, if there is no documentation that the prior anti-TB treatment was appropriate in duration and type

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: Active<br> | Drug: NNC0215-0384<br>* I.v.(intravenous) dose-escalation. Highest dose planned for i.v. administration is 10 mg/kg<br>Drug: NNC0215-0384<br>* The s.c. (subcutaneous, under the skin) part will not start until at least two i.v. dose levels have been evaluated for safety and pharmacokinetics. Highest dose planned for s.c. administration is 4 mg/kg<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Administered i.v.(intravenous) or s.c. (subcutaneous, under the skin).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 10 weeks after trial product administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| I.v. administration: AUC, Area under the curve |  | Up to 10 weeks after drug administration | 
| I.v. administration: terminal half-life (t½) |  | Up to 10 weeks after drug administration | 
| S.c. administration: AUC, Area under the curve |  | Up to 10 weeks after drug administration | 
| S.c. administration: terminal half-life (t½) |  | Up to 10 weeks after drug administration | 
| Maximum level and duration of full C5a receptor (C5aR) occupancy by NNC0215-0384 on neutrophils |  | Up to 10 weeks after drug administration | 
| Maximum and minimum levels of relevant serum and plasma biomarkers related to NNC0215-0384 safety, efficacy or mechanism of action (MoA) |  | Up to 10 weeks after drug administration |