Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses.

Detailed Description
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Primary: Describe the efficacy of 0.25% and 0.5% topical timolol maleate Gel-forming solution (GFS) as assessed through Infantile Hemangioma (IH) changes in volume. Secondary: Describe the safety of topical timolol maleate GFS for treatment of IH.

Official Title
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Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)

Conditions
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Infantile Hemangioma

Intervention / Treatment
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* Drug: 0.25% Timolol Maleate Gel Forming Solution
* Drug: 0.5% Timolol Maleate Gel Forming Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Documented informed consent from legal guardian 0-84 days postnatal age at time of first study dose or when enrolled into the non-intervention cohort. Clinical diagnosis of superficial cutaneous or mucosal infantile hemangioma (must include all of the following): Superficial lesion in the dermis Thin <2 mm in thickness Small >=5 cm at its longest dimension and <=10cm2 Involves skin or keratinized mucosa Exclusion Criteria History of previous treatment with any pharmacologic or laser therapy for IH Ongoing therapy with an oral beta blocker or oral corticosteroid (e.g., cardiac arrhythmia, adrenal insufficiency, upper airway obstruction, tetralogy of fallot (TOF), hypertension, reactive airways disease) IH that requires systemic therapy (defined by dynamic complication scale >3) IH of the non-keratinized mucosa Infants with more than one hemangioma that requires therapy Hemodynamically significant cardiovascular disease, as determined by the investigator Known allergy to beta blockers or vehicle Heart rate <100 beats per minute at screening visit Known prenatal or postnatal diagnosis of 2nd/3rd degree atrioventricular block History of Reactive Airways Disease (RAD) Any condition which would make the participant, in the opinion of the investigator unsuitable for the study.

Ages Eligible for Study
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Maximum Age: 84 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.25% Timolol Treatment<br>Subjects assigned to this arm will be randomized to 0.25% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.25% timolol they will be changed to 0.5% timolol. | Drug: 0.25% Timolol Maleate Gel Forming Solution<br>* 50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution<br>|
| Experimental: 0.5% Timolol Treatment<br>Subjects assigned to this arm will be randomized to 0.5% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.5% timolol the treating physician will decide to either continue 0.5% timolol or withdraw the subject and begin an alternative treatment. | Drug: 0.5% Timolol Maleate Gel Forming Solution<br>* 50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution<br>|
| No Intervention: Non-Intervention Group<br>Subjects assigned to this group will not receive treatment. The subject will only be photographed on the same schedule as the intervention group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as >20% and up to 80% reduction in volumetric size of hemangioma. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls | The VAS-color is a 100 mm scale used to independently grade hemangioma color. -100 indicates hemangioma is twice as intense, 0 indicates no change, and +100 indicates complete resolution. Partial response is defined as >30% and up to 80% reduction in color of hemangioma. | 180 days | 
| Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm | The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as >20% and up to 80% reduction in volumetric size of hemangioma. | 180 days | 
| Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm | Comparison of partial response of hemangioma color (partial response or greater as assessed by VAS-color) between the two treatment arms. Partial response: >30% and up to 80% reduction in color of hemangioma. | 180 days | 
| Change in Hemangioma Dynamic Complication Scale (HDCS) | Absolute change in hemangioma dynamic complication scale from Day 0 to end of study within each treatment arm. The HDCS provides a 6-point severity grading system for 12 individual hemangioma-related complications (grade 0 represents absent to minimal; grade 5 = most severe). The total score ranges from 0-60. | baseline, day 180 | 
| Number of Participants Who Reach Partial Response, Assessed by Volume | Assess time to partial response or greater by VAS-volume, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: >20% and up to 80% reduction in volumetric size of hemangioma | 30 days, 60 days, 120 days, 180 days | 
| Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color | Assess time to partial response or greater by VAS-color, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: >30% and up to 80% reduction in color of hemangioma | 180 days | 
| Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants | Absolute change in IH-QoL score scale from Day 0 to end of study within each treatment arm. The IH-QoL score scale consists of 4 domains (physical symptom of patient, social functioning of patient, social and psychological functioning of caregiver, and emotional functioning of caregiver) and 29 items, with each item scored on a Likert scale : 0 = never a problem, 1 = almost never a problem, 2 = sometimes a problem, 3 = often a problem and 4 = almost always a problem). The total range is 0-116; the higher the total number indicates a worse outcome. | baseline, day 180 | 
| Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate | Serious adverse events and adverse events of special interest from randomization to Day 180 in infants treated with topical timolol maleate (0.25% and 0.5%) GFS for the treatment of infantile hemangioma. | up to 270 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemangioma, Infantile Hemangioma, Pharmacokinetics