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

NCT02913612 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00068212
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

Infantile Hemangioma

Keywords

Hemangioma; Infantile Hemangioma; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

  180 days

• Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm

  180 days

• Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm

  180 days

• Change in Hemangioma Dynamic Complication Scale (HDCS)

  baseline, day 180

• Number of Participants Who Reach Partial Response, Assessed by Volume

  30 days, 60 days, 120 days, 180 days

Other Outcomes (4)

• Pharmacokinetics (PK) Analysis Measuring Maximum Concentration of Timolol in Plasma Specimen

  Up to 12 hours

• Pharmacokinetics (PK) Analysis Measuring Area Under the Curve of Timolol in Plasma Specimen

  Up to 12 hours

• Pharmacokinetics (PK) Analysis Measuring Volume of Distribution of Timolol in Plasma Specimen

  Up to 12 hours

Study Arms (3)

0.25% Timolol Treatment

EXPERIMENTAL

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

0.5% Timolol Treatment

EXPERIMENTAL

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

Non-Intervention Group

NO INTERVENTION

Subjects assigned to this group will not receive treatment. The subject will only be photographed on the same schedule as the intervention group.

Interventions

0.25% Timolol Maleate Gel Forming Solution DRUG

50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution

0.25% Timolol Treatment

0.5% Timolol Maleate Gel Forming Solution DRUG

50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

0.5% Timolol Treatment

Eligibility Criteria

• Age: Up to 84 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Documented informed consent from legal guardian
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kanecia Obie Zimmerman: lead
• The Emmes Company, LLC: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (12)

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadephia

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas Medical School at Houston

Houston, Texas, 77030, United States

Location

DCOL Center for Clinical Research

Longview, Texas, 75605, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related 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.

  PMID: 30790601 BACKGROUND

MeSH Terms

Conditions

Hemangioma, Capillary; Hemangioma

Condition Hierarchy (Ancestors)

Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Kanecia Zimmerman, MD, PhD, MPH
• Organization: Duke Clinical Research Institute

kanecia.zimmerman@duke.edu

919-668-8651

Study Officials

• Kanecia Zimmerman, MD, MHS

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

• Kristin Holland, MD

  Medical College of Wisconsin

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: September 26, 2016
• Study Start: May 5, 2017
• Primary Completion: October 20, 2020
• Study Completion: October 20, 2020
• Last Updated: March 12, 2024
• Results First Posted: November 15, 2022

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)