Study to Demonstrate the Efficacy and Safety of Propranolol Oral Solution in Infants With Proliferating Infantile Hemangiomas Requiring Systemic Therapy

Study Overview
=================
Brief Summary
-----------------
There is an unsatisfied medical need for a first-line treatment of proliferating IHs with a good benefit/risk profile. Based on the recent findings of encouraging results obtained with propranolol in a series of infants with severe Infantile Hemangioma (IH), propranolol is expected to be of significant benefit in the management of the condition. The present study has been designed to confirm efficacy of propranolol in severe IH by demonstrating superiority over placebo and to document the safety profile of propranolol in this indication.

Detailed Description
-----------------
Primary objective The primary objective of this study is to identify the appropriate dose and duration of propranolol treatment and demonstrate its superiority over placebo based on the complete/nearly complete resolution of target IH at W24.

Official Title
-----------------
A Randomised, Controlled, Multidose, Multicentre, Adaptive Phase II/III Study in Infants With Proliferating Infantile Hemangiomas (IHs) Requiring Systemic Therapy to Compare 4 Regimens of Propranolol (1 or 3 mg/kg/Day for 3 or 6 Months) to Placebo (Double Blind).

Conditions
-----------------
Infantile Hemangioma

Intervention / Treatment
-----------------
* Drug: Propranolol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Proliferating IH (target hemangioma) requiring systemic therapy anywhere on the body except on the diaper area with largest diameter of at least 1.5 cm Exclusion Criteria: - The patient presents with one or more of the following medical conditions: Congenital hemangioma; Kasabach-Merritt syndrome; bronchial asthma; bronchospasm; hypoglycaemia (< 40 mg/dl or at risk); untreated phaeochromocytoma; hypotension (< 50/30 mmHg); second or third degree heart block; cardiogenic shock; metabolic acidosis; bradycardia (< 80 bpm); severe peripheral arterial circulatory disturbances; Raynaud's phenomenon; sick sinus syndrome; uncontrolled heart failure or Prinzmetal's angina; documented PHACES syndrome with central nervous system involvement The patient has previously been treated for IH, including any surgical and/or medical procedures (e.g. laser therapy) The patient is known to have a hypersensitivity to propranolol and/or any other beta-blockers One or more of the following types of IH are present: Life-threatening IH Function-threatening IH (e.g. those causing impairment of vision, respiratory compromise caused by airway lesions, etc.) Ulcerated IH (whatever the localisation) with pain and lack of response to simple wound care measures 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) LVEF (left ventricular systolic function) ≤40% and/or cardiomyopathy and/or hereditary arrhythmia disorder

Ages Eligible for Study
-----------------
Minimum Age: 35 Days
Maximum Age: 150 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol oral solution<br> | Drug: Propranolol<br>* Propranolol (1 or 3 mg/kg/day for 3 or 6 months)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Treatment with placebo for 6 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interim Analysis : Complete/Nearly Complete Resolution of the Target Infantile Hemangioma at Week 24 Compared to Baseline Based on the Intra-patient Blinded Centralized Independent Qualitative Assessments of Week 24 Photographs. |  | 6 months | 
| Primary Analysis : Complete/Nearly Complete Resolution of the Target Infantile Hemangioma at W24 Compared to Baseline Based on the Intra-patient Blinded Centralized Independent Qualitative Assessments of W24 Photographs. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success/Failure Based on the Investigator Qualitative Assessment of Complete Resolution at W48. | Time to first sustained improvement based on centralized qualitative assessments of paired patient-visits | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infantile Hemangioma, Propranolol