Skip to main content
OpenTrials
Completed

NCT Number: NCT02913612

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

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Infantile Hemangioma Hemangioma Hemangioma, Capillary Neoplasms Neoplasms by Histologic Type Neoplasms, Vascular Tissue

Age range

Up to 84 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

0.25% Timolol Maleate Gel Forming Solution

Drug

50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution

0.5% Timolol Maleate Gel Forming Solution

Drug

50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

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

    Time frame: 180 days

    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.

Secondary outcomes

  1. 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

    Time frame: 180 days

    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.

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

    Time frame: 180 days

    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.

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

    Time frame: 180 days

    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.

  4. Change in Hemangioma Dynamic Complication Scale (HDCS)

    Time frame: baseline, day 180

    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.

  5. Number of Participants Who Reach Partial Response, Assessed by Volume

    Time frame: 30 days, 60 days, 120 days, 180 days

    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

  6. Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color

    Time frame: 180 days

    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

  7. Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants

    Time frame: baseline, day 180

    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.

  8. Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate

    Time frame: up to 270 days

    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.

Other outcomes

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

  4. Pharmacokinetics (PK) Analysis Measuring Clearance of Timolol in Plasma Specimen

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Kanecia Obie Zimmerman

Other

Collaborators

  • National Institutes of Health (NIH)
  • The Emmes Company, LLC

Registry information

Official study title

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

Acronym: TIM01

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Sep 26, 2016
Registry last updated
Mar 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.