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

• ClinicalTrials.gov Identifier: NCT01056341
• Recruitment Status: Completed
• First Posted: January 26, 2010
• Results First Posted: June 24, 2014
• Last Update Posted: December 10, 2015
• Sponsor: Pierre Fabre Dermatology
• Information provided by (Responsible Party): Pierre Fabre Dermatology

Tracking Information

• First Submitted Date: January 24, 2010
• First Posted Date: January 26, 2010
• Results First Submitted Date: April 9, 2014
• Results First Posted Date: June 24, 2014
• Last Update Posted Date: December 10, 2015
• Study Start Date: January 2010
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2014)

• 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. [ Time Frame: 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. [ Time Frame: 6 months ]

• Original Primary Outcome Measures (submitted: January 24, 2010): Complete/nearly complete resolution of the target IH at W24 compared to baseline based on the intra-patient blinded centralised independent qualitative assessments of W24 photographs. [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: May 21, 2014)

Success/Failure Based on the Investigator Qualitative Assessment of Complete Resolution at W48. [ Time Frame: 6 months ]

Time to first sustained improvement based on centralized qualitative assessments of paired patient-visits

• Original Secondary Outcome Measures (submitted: January 24, 2010): -Success/failure based on the investigator qualitative assessment of complete resolution at W48. -Time to first sustained improvement based on centralised qualitative assessments of paired patient-visits [ Time Frame: 6 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Demonstrate the Efficacy and Safety of Propranolol Oral Solution in Infants With Proliferating Infantile Hemangiomas Requiring Systemic Therapy
• 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).
• 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Infantile Hemangioma

Intervention

• Drug: Propranolol
  Propranolol (1 or 3 mg/kg/day for 3 or 6 months)
• Drug: Placebo
  Treatment with placebo for 6 months

Study Arms

• Experimental: Propranolol oral solution
  Intervention: Drug: Propranolol
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Publications *

• Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819.
• Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, Lipsker D, Dupuis E, Ezzedine K, Vergnes P, Taïeb A, Léauté-Labrèze C. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics. 2009 Sep;124(3):e423-31. doi: 10.1542/peds.2008-3458. Epub 2009 Aug 10.
• Léauté-Labrèze C, Hoeger P, Mazereeuw-Hautier J, Guibaud L, Baselga E, Posiunas G, Phillips RJ, Caceres H, Lopez Gutierrez JC, Ballona R, Friedlander SF, Powell J, Perek D, Metz B, Barbarot S, Maruani A, Szalai ZZ, Krol A, Boccara O, Foelster-Holst R, Febrer Bosch MI, Su J, Buckova H, Torrelo A, Cambazard F, Grantzow R, Wargon O, Wyrzykowski D, Roessler J, Bernabeu-Wittel J, Valencia AM, Przewratil P, Glick S, Pope E, Birchall N, Benjamin L, Mancini AJ, Vabres P, Souteyrand P, Frieden IJ, Berul CI, Mehta CR, Prey S, Boralevi F, Morgan CC, Heritier S, Delarue A, Voisard JJ. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med. 2015 Feb 19;372(8):735-46. doi: 10.1056/NEJMoa1404710.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 13, 2015): 512
• Original Estimated Enrollment (submitted: January 24, 2010): 470
• Actual Study Completion Date: November 2013
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Days to 150 Days (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czech Republic, France, Germany, Hungary, Italy, Lithuania, Mexico, New Zealand, Peru, Poland, Romania, Russian Federation, Spain, United States

Administrative Information

• NCT Number: NCT01056341
• Other Study ID Numbers: V00400 SB 201 Study
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pierre Fabre Dermatology
• Study Sponsor: Pierre Fabre Dermatology
• Collaborators: Not Provided

Investigators

• Study Chair: Christine Labreze, MD; Hopital de Bordeaux

• PRS Account: Pierre Fabre Dermatology
• Verification Date: November 2015