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

March 10, 2024 updated by: Kanecia Obie Zimmerman

Efficacy, Safety, and Pharmacokinetics of 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann and Robert H. Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadephia
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Medical School at Houston
      • Longview, Texas, United States, 75605
        • DCOL Center for Clinical Research
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 2 months (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
180 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
180 days
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.
180 days
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.
180 days
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.
baseline, day 180
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
180 days
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.
up to 270 days
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
30 days, 60 days, 120 days, 180 days
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.
baseline, day 180

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Up to 12 hours
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.
Up to 12 hours
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.
Up to 12 hours
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.
Up to 12 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kanecia Obie Zimmerman

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institutes of Health (NIH)
The Emmes Company, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kanecia Zimmerman, MD, MHS, Duke Clinical Research Institute
  • Study Chair: Kristin Holland, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 5, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 20, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 20, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 12, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00068212

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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