E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Proliferating localised uncomplicated infantile hemangioma not requiring systemic therapy |
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E.1.1.1 | Medical condition in easily understood language |
Proliferating localised uncomplicated infantile hemangioma |
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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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019400 |
E.1.2 | Term | Hemangioma of skin and subcutaneous tissue |
E.1.2 | System Organ Class | 100000004864 |
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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 assess propranolol gel efficacy in terms of complete/nearly complete resolution of the Infantile Hemangioma at W12 compared to baseline.
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E.2.2 | Secondary objectives of the trial |
Efficacy objectives: To assess propranolol gel efficacy in terms of complete/nearly complete resolution of the IH at W4, W8 and Week 24 compared to baseline To evaluate the parent(s) or guardian(s) on-site qualitative assessments To assess the persistence of efficacy 12 weeksafter the end of treatment.
Safety objective: To assess the safety profile and the local tolerance of the propranolol gel
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient will be eligible if he/she meets all of the following criteria: • Written informed consent(s) for study participation and the use of the patient’s images are obtained according to national regulations from the patient’s parent(s) or legal guardian(s) prior to performing any study procedures. • The patient is 35 to 150 days old inclusive, at inclusion. • Only one proliferating IH is present anywhere on the body except on the head, the neck, the hands and on the diaper area, with largest diameter ≥ 1cm and ≤ 5 cm. • If required by national regulations, patient registered with a social security or health insurance system and/or whose parent(s) or legal guardian(s) is (are) registered with a social security or health insurance system.
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E.4 | Principal exclusion criteria |
A patient will be ineligible if he/she meets any of the following criteria: • The patient has got more than one IH with largest diameter ≥ 1cm • The patient has a medically unstable health status that may interfere with his/her ability to complete the study. • IH requires, according to Investigator’s judgment, a systemic treatment. • The patient is known to have one or more of the following medical conditions: bronchial asthma; bronchospasm; hypoglycaemia; untreated phaeochromocytoma; hypotension; second or third degree heart block; cardiogenic shock; metabolic acidosis; bradycardia; severe peripheral arterial circulatory disturbances; Raynaud’s phenomenon; sick sinus syndrome; uncontrolled heart failure or Prinzmetal’s angina. • The patient has received at least one of the following prohibited medications within 14 days before randomisation: - Cardiovascular treatments: anti-arrhythmics, calcium channel blockers, ACE inhibitors, inotropic agents, vasodilators (hydralazine hydrochloride…), clonidine… - Hypoglycaemic agents or drugs able to induce hypoglycaemia. - Non-steroid anti-inflammatory drugs (NSAIDs) at anti-inflammatory dose. - Sympathomimetic agents and parenteral adrenaline. - Anaesthetic agents, lidocaïne (the prohibition period is shortened to 48 hours, if anaesthesia has been performed for diagnosis investigation e.g. MRI…) - Inducers of hepatic drug metabolism or substrates or inhibitors of CYP2D6, CYP1A2, CYP2C19 - Anti-ulcer drugs (cimetidine, ranitidine, proton pomp inhibitors other than omeprazole and lanzoprazole) - Metoclopramide - Benzodiazepines - Neuroleptic drugs (chlorpromazine, sultopride hydrochloride...) - Other drugs: triptans, ergotamine, theophylline, warfarin, thyroxine, floctafenine
• The patient has previously been administered systemic, intralesional or topical corticosteroids, vincristine, alfa-interferon, imiquimod, propranolol or other beta-blockers. • The patient has previously been administered treatment for IH or surgical and/or medical procedures (e.g. laser therapy) have been performed to treat the IH. • The patient’s mother has been breastfeeding the patient while she was also being treated with beta-blockers (including propranolol) or, she has been breastfeeding the patient within 14 days of randomisation while she was also being treated with systemic (oral, intra-venous or intra-muscular) corticosteroids, vincristine or alfa-interferon. • The patient is known to have a hypersensitivity to propranolol and/or any other beta-blockers and/or any ingredient of the test product. • Patient with congenital hemangioma • Patient with ulcerated IH. • Patient with heart rate < 80 bpm at inclusion • Patient with blood pressure < 50/30 mmHg at inclusion • Patient with known renal impairment. • Patient with known cardiac conditions that may predispose to heart block. • The patient has previously experienced an anaphylactic reaction • The patient was born prematurely and has not yet reached his/her term equivalent age (e.g. an infant born 2 months prematurely cannot be included before the age of 2 months) • Patient with cardiomyopathy. • The patient is participating in another clinical study or has received treatment with known remnant effects or undergone investigation liable to interfere with the present clinical trial. • The patient has sibling already participating to this clinical study • Parent(s) or legal guardian(s) who cannot be contacted by telephone in case of emergency.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy criterion is the evolution of IH from baseline to W12. The binary primary endpoint (success/failure) will be evaluated based on the intra-patient blinded centralised independent qualitative assessments of W12 photographs of the IH compared to baseline. A treatment success will be defined as a centralised assessment of complete/nearly complete resolution of the IH at W12 compared to baseline, where nearly complete resolution is defined as a minimal degree of telangiectasis, erythema, skin thickening, soft tissue swelling and/or distortion of anatomical landmarks. |
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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) |
Secondary efficacy criteria: • Centralised assessments of complete/nearly complete resolution of the IH at W4, W8 and W24 compared to baseline,. • Investigator on-site qualitative assessments - At each scheduled post-baseline visit compared to baseline categorical endpoints for complete/nearly complete resolution - At week 4, week 8, week 12 and week 24 compared to baseline categorical endpoints for IH evolution (4-points scale: complete resolution, improvement, stabilisation, worsening) - At each scheduled post-baseline visit compared to the previous schedule visit, categorical endpoints for IH evolution (4-points scale: complete resolution, improvement, stabilisation, worsening) • Parent(s) or guardian(s) on-site qualitative assessments at each scheduled post-baseline visit compared to the previous scheduled visit - Categorical endpoints for IH evolution (4-points scale: complete resolution, improvement, stabilisation, worsening)
Persistence of efficacy criteria: • Persistence of complete/nearly complete resolution of the IH at W24 compared to W12 based on centralised assessments. • Investigator qualitative assessments by categorical endpoints for hemangioma evolution (4-points scale: complete resolution, improvement, stabilisation, worsening) at Week 24 (3 months after end of treatment).
Safety criteria: • Safety endpoints will be based on the following evaluations: - Adverse events (AE) - Height, weight, head circumference, temperature, heart rate, blood pressure, respiratory rate, pulmonary auscultation, liver palpation and global physical examinations (all visits) • Local tolerability - Very good tolerance : no subjective sign or physical sign of local side effects - Good tolerance : transitory subjective signs, without physical sign or necessary modification of the frequency of product application - Poor tolerance : persisting subjective signs or physical signs of local side effects, leading to modification of the frequency of the product application but no treatment discontinuation - Very poor tolerance: subjective and/or physical signs leading to treatment discontinuation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy criteria: W4, W8, W12 and W24 compared to baseline Persistence of efficacy criteria: W24 compared to W12 |
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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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |