E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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 evaluate the change in disease activity following 12 weekly s.c. doses of NNC109-0012 3mg/kg compared to placebo in subjects with active RA on stable background MTX therapy. |
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E.2.2 | Secondary objectives of the trial |
• To assess signs of clinical efficacy as determined by change in disease activity (ACR
scores), clinical responses (EULAR response criteria) and PD biomarkers during and after 12 repeated doses of NNC109-0012
• To assess safety and tolerability during and after 12 repeated doses of NNC109-0012
• To assess the pharmacokinetic (PK) profile of NNC109-0012 after 12 repeated doses of NNC109-0012
• To assess potential immunogenicity of NNC109-0012 during and after 12 repeated doses of NNC109-0012. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A diagnosis of RA according to the American College of Rheumatology (ACR1987
classification) made at least 3 month’s prior to screening.
2. Active RA, characterised by a DAS28-CRP ≥4.5 and ≥ 5 swollen and ≥ 5 tender joints of the 28 joint count
3. Methotrexate treatment (≥7.5 mg - ≤ 25 mg/week) for at least 12 weeks, with a stable dose for at least 4 weeks prior to screening
4. Aged between 18 and 75 years (both years inclusive)
5. Male and female subjects must be willing to avoid pregnancy and breast feeding throughout this trial at least until 15 weeks following the last dose of study medication
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E.4 | Principal exclusion criteria |
1. Body mass index (BMI) < 18.5 or > 35.0 kg/m2
2. Subjects with chronic inflammatory autoimmune disease other than RA
3. History of or current inflammatory joint disease other than RA (e.g. gout, psoriatic or reactive arthritis, Lyme disease, juvenile ideopathic arthritis)
4. Chronic or ongoing infectious disease requiring systemic anti-infectious treatment within 2 weeks prior to screening
5. History of severe systemic bacterial, viral or fungal infections within the past 12 months prior to screening
6. Evidence of herpes zoster or cytomegalovirus infection that resolved less than 2 months prior to screening
7. Past or current malignancy
8. An adequate treatment duration of a biologic DMARD with an inadequate response (treatment failure) defined at the Investigator’s discretion
9. Clinically significant cardiac or cardiovascular disease
10. Positive for human immunodeficiency virus (HIV)
11. Positive test (serology and/or PCR) results for Hepatitis B or Hepatitis C
12. Positive purified protein derivative (PPD) tuberculin skin test
13. Blood donation or blood loss of more than 0.45 L within 2 months prior to screening, or longer if required by local regulations
14. Breast-feeding women |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in DAS28-CRP from baseline to week 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Terminal serum half-life (t½)
Serum levels of NNC109-0012 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |