|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Early diffuse cutaneous systemic sclerosis
|Medical condition in easily understood language
|Early (within 3 years of onset) diffuse cutaneous scleroderma
|Diseases [C] - Musculoskeletal Diseases [C05]
|E.1.2 Medical condition or disease under investigation
|Diffuse systemic sclerosis
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The primary objective is to determine the efficacy of moderate dose prednisolone, compared with placebo treatment, in reducing pain and disability, and improving skin score (reducing skin thickening) in patients with early diffuse cutaneous systemic sclerosis. Also to determine whether moderate dose prednisolone is a safe therapy in patients with early diffuse cutaneous systemic sclerosis, with particular reference to renal function. Efficacy and safety will be evaluated over a 6 month treatment period.
|Secondary objectives of the trial
|Trial contains a sub-study
|Principal inclusion criteria
|1) Patients presenting with dcSSc with skin involvement extending to the proximal limb and/or trunk.
2) Male or female age ≥ 18 years.
3) Skin involvement of less than 3 years defined by patient report or clinician opinion.
4) Patient is able and willing to follow with the requirements of the study.
5) Fully written informed consent.
|Principal exclusion criteria
|1) Patients with significant uncontrolled Stage 1 Hypertension (clinic BP >140/90mmHg). Patients with previous hypertension which is controlled (clinic BP <140/90mmHg) for at least 4 weeks are considered eligible.
2) Previous renal crisis or significant renal impairment (estimated Glomerular Filtration Rate (eGFR) < 40 ml/min).
3) Patients currently on steroid therapy, or previous steroid therapy within the last 4 weeks, with the exception of inhaled steroids for respiratory diseases.
4) Patients currently participating in another randomised controlled trial of an investigational agent or device, or previous participation within the last 30 days.
5) Patients currently receiving an immunosuppressant or biologic therapy the dose of which has changed in the last 4 weeks, or is likely to change during the first 3 months of study treatment.
6) Patients with major myositis or inflammatory arthritis. Patients with low level myositis or inflammatory arthritis are eligible for inclusion (for example, in the case of myositis, a creatine kinase less than 4 times the upper limit of normal or myositis only demonstrable on magnetic resonance imaging).
7) Female patients who are pregnant at time of screening.
8) Patients with significant inflammatory bowel disease as judged by the investigator.
9) It is important that patients do not suddenly stop taking the study medication. Patients who do not fully understand this, will be excluded.
|E.5 End points
|Primary end point(s)
|There will be two co-primary outcome measures:
1. The difference in mean HAQ-DI at 3 months.
2. The difference in mRSS at 3 months.
Functional ability and reduced pain are captured by the Health Assessment Questionnaire Disability Index. Skin score is often the primary outcome measure in trials of early diffuse cutameous systemic sclerosis, because it reflects the overall disease process and is a predictor of outcome. Both Health Assessment Questionnaire Disability Index and modified Rodnan Skin Score are validated in systemic sclerosis as per OMERACT (Outcome Measures in Rheumatologic Clinical Trials) criteria.
|Timepoint(s) of evaluation of this end point
|The co-primary outcome measures will be assessed at baseline and again at 3 months.
|Secondary end point(s)
|There are a number of secondary outcome measures which focus on pain, disability and quality of life. These include assessments of pain, itch, hand function, fatigue, helplessness, arthritis index and percentage change in skin score.
|Timepoint(s) of evaluation of this end point
|The secondary outcomes will be assessed at baseline and again at 6 weeks, 3 months and 6 months.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
Exceptions to this are when continued pharmacovigilance reporting is deemed necessary. If a serious adverse event remains on-going at the end of Visit 5, this should be followed and documented until resolution.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days