E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
(very early) systemic sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
(very early) systemic sclerosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the changes of high dose intravenous methylprednisolone on nail fold capillaries as measured by nail fold capillary microscopy (NCM) at week 12. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective: To investigate the effects of glucocorticoids on signs and symptoms of disease progression.
Tertiary objective:To analyze the effect of glucocorticoids on inflammatory biomarkers that have been implicated in SSc pathogenesis and in the response of systemic autoimmune diseases to glucocorticoids. These biomarkers are the interferon signature in peripheral blood cells and the soluble inflammatory mediators platelet factor 4 (CXCL4), interleukin-1β, interleukin-6, tumor necrosis factor-α, endothelin-1, intercellular adhesion molecule-1 and vascular endothelial growth factor (2, 15-19). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years
- Fulfilling VEDOSS criteria: Raynauds' Phenomenon and Positive for disease specific auto antibodies and Systemic sclerosis specific nail fold capillaroscopic findings
- Puffy fingers < 3 years duration
- Modified Rodnan Skin Score = 0
- Written informed consent |
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E.4 | Principal exclusion criteria |
- Presence of acrosclerosis, acrosteolysis and digital ulcers
- Presence of anti-RNA polymerase III auto antibodies
- Previous systemic treatment for SSc, namely methotrexate, prednisone (> 14 days in previous 6 months), mofetyl mycophenolate and cyclophosphamide
- Clinically significant internal organ involvement: DLCO < 80% predicted, VC < 70% predicted, renal dysfunction with GFR < 60 ml/min, diastolic dysfunction > grade 1 on echocardiography, pulmonary hypertension, weight loss > 10% in the last 6 months with unknown cause
- Usage of medication that influences CYP3A4 (eg carbamazepine / fenobarbital / fenytoïne / rifampicine/itraconazol e/ claritromycine / erytromycine / HIV – proteaseinhibitors) and hypersensitivity for methylprednisolone
- Contra-indications for methylprednisolone, such as pregnancy, lactation, psychotic or depressive disorder, ulcus duodeni or ventriculi, untreated hypertension (> 160-90 mmHg) or acute infections |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the change in capillary density between baseline and follow-up visits. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline (= week 0), week 4, week 8, week 12, month 6, month 9, month 12, month 18, month 24, month 30 and month 36 |
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E.5.2 | Secondary end point(s) |
The secondary outcomes of this study are: change in selected biomarkers: the interferon signature in peripheral blood cells CXCL4, IL-1β, IL-6, TNF-α, ET-1, ICAM-1 and VEGF; change in nail fold capillary changes other than capillary density and giant capillaries; changes in nail fold capillary pattern (early, active, late, normal); change in modified Rodnan skin score; presence of puffy fingers; presence of synovitis, presence of tendon friction rubs; fulfilling EULAR/ACR classification criteria for SSc (24), pulmonary function tests; presence of interstitial lung disease; suspicion of PH; and physical function, general health and utilities as measured by the SHAQ, SF-36, EQ5D and GIT. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline (= week 0), week 4, week 8, week 12, month 6, month 9, month 12, month 18, month 24, month 30 and month 36 |
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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 | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
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
| 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 | 2 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |