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 |
RA, Rheumatoid arthritis, autoimmune disease that causes chronic joint inflammation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
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 explore the potential differences in the mechanism of action through analysis of synovial biopsies in subjects with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) after 12 weeks of treatment with NNC0109-0012 and adalimumab |
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E.2.2 | Secondary objectives of the trial |
• To compare joint changes measured by magnetic resonance imaging (MRI) scans and ultrasound in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab
• To compare changes in disease activity in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab
• To describe the safety and tolerability of NNC0109-0012 and adalimumab in subjects with active RA and an inadequate response to MTX
• To compare changes in biomarkers in blood and synovial biopsies in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab
• To compare changes measured by MRI scans and ultrasound, disease activity, biomarkers in blood and the safety and tolerability in subjects with active RA and an inadequate response to MTX after 12 weeks of treatment with NNC0109-0012 and adalimumab and additional 12 weeks of follow up
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female age ≥18 and ≤ 75 years at the time of signing informed consent.
2. A diagnosis of RA at least 6 months prior to screening visit, according to the American College of Rheumatology (EULAR/ACR 2010 criteria) or by standard criteria (ACR 1987) if diagnosis was made earlier than 2010.
3. Subjects with ACR global functional status of 1 to 3
4. Active RA, characterised by:
• DAS28 (CRP) > 4.5 and
• ≥ 6 tender and ≥ 6 swollen joints based on a 66/68 joint count
5. Active Synovitis in at least two joints of the wrist and metacarpophalangeal joints, as assessed by high frequency Power Doppler ultrasound scan at screening and randomisation |
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E.4 | Principal exclusion criteria |
1. Subjects with arthritis due to other autoimmune diseases than RA
2. Body weight > 90.0 kg
3. History of or current inflammatory joint disease other than RA (e.g. gout, psoriatic or reactive arthritis, Lyme disease, juvenile idiopathic arthritis, excluding secondary Sjogren syndrome and hypothyroidism)
4. Any active or on-going bacterial infections within 4 weeks prior to screening visit, unless treated and resolved with appropriate therapy or any history of recurrent infections or conditions predisposing to chronic infections (e.g., bronchiectasis, chronic osteomyelitis)
5. Subjects with malignancy within the previous 5 years with the exception of adequately treated and cured basal or squamous cell carcinoma of the skin or cervical carcinoma in situ occurring more than 12 months prior to screening visit
6. Female who is pregnant, breast feeding, intends to become pregnant or is of childbearing potential, not willing to use two highly effective contraceptive methods (adequate highly effective contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system) one of which has to be a barrier method a barrier method of contraception (e.g. condom with spermicidal foam/gel/film/cream), for at least 16 weeks (approximately 5 half-lives) following the last dose of trial medication
7. Male subjects who are sexually active and not surgically sterilised, who or whose partner are unwilling to use two different forms of highly effective contraception, one of which has to be a barrier method a barrier method of contraception (e.g. condom with spermicidal foam/gel/film/cream) for the duration of the trial and for at least 16 weeks (approximately 5 half-lives) following the last dose of trial medication
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the total histopathological synovitis score. |
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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) |
Efficacy endpoints
• Change in dynamic contrast enhanced MRI (DCE-MRI) measures of initial rate of enhancement (IRE)
• Change in dynamic contrast enhanced MRI (DCE-MRI) measures of maximal enhancement (ME)
• Changes in RA-MRI scores (RAMRIS) of synovitis
• Changes in RA-MRI scores (RAMRIS) of oedema
• Changes in RA-MRI scores (RAMRIS) of erosion
• Change in high frequency ultrasound with Power Doppler measures of total synovitis
• Change in high frequency ultrasound with Power Doppler measures of total tenosynovitis scores
• Change in disease activity 28 – C-reactive protein (DAS28 (CRP)
Safety and tolerability endpoints
1• Incidence of Adverse Events (AE)
2• Incidence of local intolerability at the injection site
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints
• From baseline to Week 12
Safety and tolerability endpoints
1• From baseline to Week 24
2• From baseline until Week 24 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |