Inflammation, Rheumatoid Arthritis
Conditions
Brief summary
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).
Interventions
DRUGNNC0215-0384
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.
DRUGplacebo
Placebo administered corresponding to NNC0215-0384 treatment
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events (AEs) | From first dosing until 19 weeks after first dosing |
Secondary
| Measure | Time frame |
|---|---|
| Concentration of NNC0215-0384 in serum | 7 days after each 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 |
Countries
Germany, Hungary, Poland, Russia
Outcome results
None listed