TIM01: Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)

• Sponsor: Kanecia Zimmerman, MD MPH (Other)
• Overall Status: Completed
• CT.gov ID: NCT02913612
• Collaborator: The Emmes Company, LLC (Industry), National Institutes of Health (NIH) (NIH)
• Enrollment: 105
• Locations: 12
• Arms: 3
• Actual Duration (Months): 41.5
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Infantile Hemangioma	Drug: 0.25% Timolol Maleate Gel Forming Solution; Drug: 0.5% Timolol Maleate Gel Forming Solution	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)
• Actual Study Start Date: May 5, 2017
• Actual Primary Completion Date: Oct 20, 2020
• Actual Study Completion Date: Oct 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.25% Timolol Treatment 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; 50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution
Experimental: 0.5% Timolol Treatment 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; 50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution
No Intervention: Non-Intervention Group Subjects assigned to this group will not receive treatment. The subject will only be photographed on the same schedule as the intervention group.

Outcome Measures

Primary Outcome Measures

1. Comparison of partial response of hemangioma volume within the treat arm compared to the untreated controls [180 days]

   Partial response of hemangioma volume from baseline to 180 days within each treatment arm and compared with untreated controls

Secondary Outcome Measures

1. Efficacy Comparison of proportion of infants with partial response or greater change in volume [180 days]

   Percentage of participants with partial response of change in volume from baseline to 180 days within each treatment arm compared with the untreated controls.

2. Efficacy comparison of proportion of infants with partial response between the two treatment arms [180 days]

   Percentage of participants with partial response of change in color from baseline to 180 days between the two treatment arms and compared with untreated controls

3. Efficacy comparison of partial response of infants with partial response of hemangioma color between the treatment arms [180 days]

   Percentage of participants with partial response of change in color from baseline to 180 days between the two arms.

4. Change in Efficacy Improvement of hemangioma complication within the treatment arms [Baseline and Day 180]

   Change in the dynamic complication scale results within each treatment arm

5. Efficacy assessment of time to partial response in both treatment arms [180 days]

   Assess time to partial response by comparing baseline to day 30, day 60, day 120 and 120 in both treatment arms

6. Change in Efficacy assessment of Quality of Life assessment for infants in both treatment arms [Baseline and Day 180]

   Absolute change in the Quality of Life score within each treatment arm

7. Rate of Serious Adverse Events and Adverse Events of special interest in treated infants in both arms [270 days]

   Rate of serious adverse events and adverse events of special interest for infants in both treatment arms

8. Pharmacokinetics (PK) Analysis measuring clearance of Timolol in Plasma specimen [Up to 12 hours]

   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.

9. Pharmacokinetics (PK) Analysis measuring Volume of Distribution of Timolol in plasma specimen [Up to 12 hours]

   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.

10. Pharmacokinetics (PK) Analysis measuring area under the curve of Timolol in plasma specimen [Up to 12 hours]

    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.

11. Pharmacokinetics (PK) Analysis measuring maximum concentration of Timolol in plasma specimen [Up to 12 hours]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 84 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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):

4. Superficial lesion in the dermis

5. Thin <2 mm in thickness

6. Small >=5 cm at its longest dimension and <=10cm2

7. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
2	Indiana University Health	Indianapolis	Indiana	United States	46202
3	Johns Hopkins Medical Center	Baltimore	Maryland	United States	21287
4	Boston Children's Hospital	Boston	Massachusetts	United States	02115
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
7	Columbia University Medical Center	New York	New York	United States	10032
8	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
9	Children's Hospital of Philadephia	Philadelphia	Pennsylvania	United States	19104
10	The University of Texas Medical School at Houston	Houston	Texas	United States	77030
11	DCOL Center for Clinical Research	Longview	Texas	United States	75605
12	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Kanecia Zimmerman, MD MPH
• The Emmes Company, LLC
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Kanecia Zimmerman, MD, MHS, Duke Clinical Research Institute
• Study Chair: Kristin Holland, MD, Medical College of Wisconsin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kanecia Zimmerman, MD MPH, Principal Investigator, Duke University
• ClinicalTrials.gov Identifier: NCT02913612
• Other Study ID Numbers: Pro00068212
• First Posted: Sep 26, 2016
• Last Update Posted: Jan 24, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kanecia Zimmerman, MD MPH, Principal Investigator, Duke University: Hemangioma; Infantile Hemangioma; Pharmacokinetics
• Additional relevant MeSH terms: Hemangioma; Hemangioma, Capillary; Port-Wine Stain; Timolol; Pharmaceutical Solutions; Maleic acid

Study Results

No Results Posted as of Jan 24, 2022