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

Infantile Hemangioma Clinical Trial

— TIM01  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02913612
• Other study ID #: Pro00068212
• Status: Completed
• Phase: Phase 2
• Start date: May 5, 2017
• Est. completion date: October 20, 2020

Study information

• Verified date: March 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: October 20, 2020
• Est. primary completion date: October 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 84 Days

Eligibility

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.

Related Conditions & MeSH terms

• Hemangioma
• Hemangioma, Capillary
• Infantile Hemangioma
• Port-Wine Stain

Intervention

Drug:
• 0.25% Timolol Maleate Gel Forming Solution
50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution
• 0.5% Timolol Maleate Gel Forming Solution
50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

Locations

Country	Name	City	State
United States	Johns Hopkins Medical Center	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The University of Texas Medical School at Houston	Houston	Texas
United States	Indiana University Health	Indianapolis	Indiana
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of Philadephia	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Kanecia Obie Zimmerman	National Institutes of Health (NIH), The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetics (PK) Analysis Measuring Maximum Concentration of Timolol in Plasma Specimen	The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.	Up to 12 hours
Other	Pharmacokinetics (PK) Analysis Measuring Area Under the Curve of Timolol in Plasma Specimen	The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.	Up to 12 hours
Other	Pharmacokinetics (PK) Analysis Measuring Volume of Distribution of Timolol in Plasma Specimen	The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.	Up to 12 hours
Other	Pharmacokinetics (PK) Analysis Measuring Clearance of Timolol in Plasma Specimen	The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.	Up to 12 hours
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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