E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The target population for therapeutic intervention will be subjects who carry serum autoantibodies (antibodies to citrullinated protein antigens – ACPA; rheumatoid factor – RF) and who have joint pains (arthralgia) but no joint swelling. These subjects are deemed to be at highest risk of developing rheumatoid arthritis. |
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E.1.1.1 | Medical condition in easily understood language |
The preclinical phase of RA. During this phase individuals are experiencing joint pains, but have not yet developed arthritis (clinically apparent joint swelling). |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003239 |
E.1.2 | Term | Arthralgia |
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 feasibility, efficacy and acceptability of abatacept therapy in subjects at high risk of developing RA. |
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E.2.2 | Secondary objectives of the trial |
To characterise immune and inflammatory responses associated with ACPA before, during and after therapy with abatacept. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female subjects, aged ≥ 18 years.
- Arthralgia that is considered to be inflammatory in nature.
- ACPA and RF positive, or high titre ACPA.
- Able and willing to give written informed consent and comply with the requirements of the study protocol. |
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E.4 | Principal exclusion criteria |
- Clinically apparent arthritis, as assessed by a rheumatologist.
- A history of inflammatory arthritis, as assessed by a rheumatologist.
- History or current use of DMARDs or biologics.
- History of oral or parenteral use of corticosteroids within the last 12 weeks.
- Co-morbidities requiring treatment with immunosuppressive or immune modulating therapy.
- Chronic illnesses that would, in the opinion of the investigator, put the subject at risk.
- Recipients of a live vaccine within 4 weeks of inclusion.
- Pregnant or breastfeeding
- Unable to give informed consent |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) The time to development of clinically apparent synovitis in ≥ 3 joints, as determined by two independent assessors with experience in clinical assessment of RA
2) The time to development of RA according to the ACR/EULAR 2010 criteria, where joint involvement is defined as joint swelling.
In either case joint swelling will be confirmed by ultrasound. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 3 months for up to 24 months |
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E.5.2 | Secondary end point(s) |
1) The development of RA according to the ACR/EULAR 2010 criteria where ultrasound
2) Assessments of disease activity and progression over time, using DAS28 (tender and swollen joint counts, patient global visual analogue score (VAS), ESR) and Extended Joint Count 68/66, Simple Disease Activity Score (SDAI) and Clinical Disease Activity Score (CDAI), Pain VAS, Lifestyle Factors Questionnaire, Health Assessment Questionnaire (HAQ), Modified Illness Perception Questionnaire (Modified IPQ-R), Euro-Quality of Life Questionnaire (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Work Instability Scale (RA-WIS) and Functional Assessment Of Chronic Illness Therapy-Fatigue (FACIT-F).
3) The proportion of participants requiring DMARD therapy, and the time to commencing DMARD therapy, including oral or parenteral corticosteroids.
4) Progression of radiographic changes in X-rays of the hands and feet scored by van der Heijde Sharpe Modified Scores or using the Larsen score.
5) Changes in scores of synovitis and vascularity defined by high resolution ultrasonography and power Doppler over time.
6) Adverse events.
The exploratory endpoints of this study are:
1) Changes in serum ACPA levels over time.
2) ACPA isotype and antigenic fine specificity over time.
3) Signatures of immune and inflammatory responses as defined through analysis of serum, peripheral blood cell subsets, peripheral blood RNA expression profiling and urine. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be evaluated every 3 months for up to 24 months
The exploratory endpoints will be evaluated at the end of the study following analysis of the biological samples. |
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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 | Yes |
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) | 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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | Yes |
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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The end of study is defined as last subject's last assessment(at 24 months). |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |