E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Raynaud phenomenon secondary to systemic sclerosis |
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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 | 10037912 |
E.1.2 | Term | Raynaud's phenomenon |
E.1.2 | System Organ Class | 10047065 - Vascular 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 determine if a single injection schedule of botulinum toxin A in both hands is more efficient than placebo to decrease the frequency of attacks in Raynaud phenomenon secondary to systemic sclerosis.
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E.2.2 | Secondary objectives of the trial |
Comparison between the 2 groups of the change (absolute) from baseline in the number of RP attacks per week at 4 weeks. An attack is defined as an episode of pallor or cyanosis (with or without pain, tingling or numbness). Subjects will keep a daily record of the number of RP attacks they experienced per day and the duration of each attack, from Day -14 to Day 0 (+/- 4 days) and from Day 14 to Day 28 ( +/- 4 days) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
" Aged 18 years and older " Diagnosed with systemic sclerosis (EULAR/ACR 2013 criteria ; or Leroy and Metsger criteria). " Symptoms of Raynaud's phenomenon affecting both hands (not necessarily to equal extents) " Frequency of Raynaud's attacks ? 5/week during cold weather " Stable dose of phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, or calcium channel blockers defined as 1-month with no change in dose " Ability to return/be available for follow-up evaluations " Ability to fill the diary " Ability/willingness to give informed consent " Affiliation to any French social security regime
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E.4 | Principal exclusion criteria |
" History of myasthenia gravis " Inflammatory myositis <2 years. " Reported allergy or hypersensitivity to any Botulinum toxin preparation or to lidocaine or other local anesthetic agent. " Active infection in either hand. " Pregnant or lactating women (female patients of child bearing potential must undergo a pregnancy test before inclusion and at treatment day). " Patients who have previously undergone any vascular surgery on the upper extremity, including surgical sympathectomy or ever received botulinum toxin. " Cognitive impairment " Iloprost scheduled the month following injectionsor 3 months before treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Comparison between the 2 groups of the change (absolute) from baseline in the number of RP attacks per week at 4 weeks. An attack is defined as an episode of pallor or cyanosis (with or without pain, tingling or numbness). Subjects will keep a daily record of the number of RP attacks they experienced per day and the duration of each attack, from Day -14 to Day 0 (+/- 4 days) and from Day 14 to Day 28 ( +/- 4 days) Secondary endpoints 1- Comparison between the 2 groups of the change (absolute) from baseline in the number of RP attacks per week at 12 and 24 weeks. 2- Comparison between the 2 groups at 4, 12 and 24 weeks of follow-up after the treatment of: - Percentage of digital ulcers with complete healing - Number of new digital ulcers. - Change in Raynaud's pain score. - Change in quality of life from baseline to weeks 4, 12 and 24. - Change in hand function from baseline to weeks 4, 12 and 24. 3- Frequency and severity of adverse events during treatment |
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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 | No |
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) | Yes |
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.8.3 |
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 | 16 |
E.8.5 | The trial involves multiple Member States | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |