Clinical trial NCT02913612: Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)
Official title: Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infantile Hemangioma
Keywords: Hemangioma
Infantile Hemangioma
Pharmacokinetics
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: The Emmes Company, LLC
name: National Institutes of Health (NIH)
First posted: 2016-09-26
Enrollment: 105
Sex: ALL
Maximum age (years): 84
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria

1. Documented informed consent from legal guardian
2. 0-84 days postnatal age at time of first study dose or when enrolled into the non-intervention cohort.
3. Clinical diagnosis of superficial cutaneous or mucosal infantile hemangioma (must include all of the following):

   1. Superficial lesion in the dermis
   2. Thin \<2 mm in thickness
   3. Small \>=5 cm at its longest dimension and \<=10cm2
   4. Involves skin or keratinized mucosa

Exclusion Criteria

1. History of previous treatment with any pharmacologic or laser therapy for IH
2. 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)
3. IH that requires systemic therapy (defined by dynamic complication scale \>3)
4. IH of the non-keratinized mucosa
5. Infants with more than one hemangioma that requires therapy
6. Hemodynamically significant cardiovascular disease, as determined by the investigator
7. Known allergy to beta blockers or vehicle
8. Heart rate \<100 beats per minute at screening visit
9. Known prenatal or postnatal diagnosis of 2nd/3rd degree atrioventricular block
10. History of Reactive Airways Disease (RAD)
11. Any condition which would make the participant, in the opinion of the investigator unsuitable for the study.

Primary outcomes:
measure: 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
timeFrame: 180 days
Secondary outcomes:
measure: 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
timeFrame: 180 days
measure: Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm
timeFrame: 180 days
measure: Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm
timeFrame: 180 days
measure: Change in Hemangioma Dynamic Complication Scale (HDCS)
timeFrame: baseline, day 180
measure: Number of Participants Who Reach Partial Response, Assessed by Volume
timeFrame: 30 days, 60 days, 120 days, 180 days
measure: Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color
timeFrame: 180 days
measure: Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants
timeFrame: baseline, day 180
measure: Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate
timeFrame: up to 270 days
Other outcomes:
measure: Pharmacokinetics (PK) Analysis Measuring Maximum Concentration of Timolol in Plasma Specimen
timeFrame: Up to 12 hours
measure: Pharmacokinetics (PK) Analysis Measuring Area Under the Curve of Timolol in Plasma Specimen
timeFrame: Up to 12 hours
measure: Pharmacokinetics (PK) Analysis Measuring Volume of Distribution of Timolol in Plasma Specimen
timeFrame: Up to 12 hours
measure: Pharmacokinetics (PK) Analysis Measuring Clearance of Timolol in Plasma Specimen
timeFrame: Up to 12 hours
Locations:
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadephia
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Medical School at Houston
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Duke Clinical Research Institute
name: Kanecia Zimmerman, MD, MHS
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Kristin Holland, MD
role: STUDY_CHAIR
References:
citation: Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee (See Acknowledgments for a listing of committee members.). Systemic timolol exposure following topical application to infantile hemangiomas. J Am Acad Dermatol. 2020 Mar;82(3):733-736. doi: 10.1016/j.jaad.2019.02.029. Epub 2019 Feb 18. No abstract available.