E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability, including immunogenicity, of NNC151-0000 after four multiple doses at up to seven dose levels in subjects with active RA
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacodynamics of NNC151-0000 (PD) including
- C5aR occupancy on neutrophils and monocytes
- effect on various biomarkers, including acute phase cytokines and immunophenotyping
• to assess the PK of NNC151-0000
• to assess the preliminary clinical improvement and efficacy of NNC151-0000 in subjects with RA using the ACR20/50/70 and ACR-N scores and DAS28.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification), made at least three months prior to randomisation.
• Active RA, characterized by a DAS28 score ≥3.2
• Male and female subjects
• Age between 18 and 75 years (both inclusive)
• Subjects are on stable doses of methotrexate (up to and including 25 mg/week) for at least 4 weeks prior to dosing |
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E.4 | Principal exclusion criteria |
1. Known or suspected allergy to trial product or related products
2. Subjects with chronic inflammatory autoimmune disease other than RA (except secondary Sjögren's syndrome or stable hypothyroidism)
3. History of or current inflammatory joint disease other than RA (eg. gout (crystal proven), psoriatic, juvenile arthritis), current reactive arthritis or Lyme disease
4. Body mass index (BMI) <18.0 or >38.0 kg/m² (inclusive)
5. Chronic or ongoing active infectious disease requiring systemic anti-infectious treatment within 2 weeks prior to randomisation
6. History of severe systemic bacterial, viral or fungal infections within the past 12 months prior to randomisation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events (AEs) and toxicity (by use of National Cancer Institute’s CTCAE scale, version 3 including
- local tolerability at injection site
- vital signs (blood pressure (BP), pulse and body temperature) and body weight
- ECG
- haematology, biochemistry including CRP, Hs-CRP and lipids, urinalysis
- acute phase cytokine response (IL-1β, IL-6, TNF-α, INF-γ)
- complement markers (e.g. C5a-desArg, C3 and total haemolytic complement titre (CH50)
- immunogenicity (antibodies to NNC151−0000). The Immunogenicity samples will be analysed at Novo Nordisk A/S. The analysis for antibodies will be performed after completion of each dose level during dose escalation.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
Denmark |
Germany |
Hungary |
Poland |
Romania |
Russian Federation |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |