Infantile HemangiomaPhase 2TIM01NCT02913612

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

A Phase 2 study testing 0.25% Timolol Maleate Gel Forming Solution and 0.5% Timolol Maleate Gel Forming Solution in people with Infantile Hemangioma, run by Kanecia Obie Zimmerman at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages Up to 84 days
Conditions the study is for: Infantile Hemangioma
What is being tested?: 0.25% Timolol Maleate Gel Forming Solution and 0.5% Timolol Maleate Gel Forming Solution
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 105 participants
Where: 12 sitesUnited States
Study dates: 5 May 2017to 20 Oct 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 84 days
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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.

Trial locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

United States12 sites

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

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Infantile Hemangioma
Being tested: 0.25% Timolol Maleate Gel Forming Solution, 0.5% Timolol Maleate Gel Forming Solution
Keywords: Hemangioma, Infantile Hemangioma, Pharmacokinetics
Medical subject headings: Hemangioma, Capillary, Hemangioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

0.25% Timolol Maleate Gel Forming SolutionDrug
50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution
0.5% Timolol Maleate Gel Forming SolutionDrug
50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

Study groups in NCT02913612
Study group	Role	What they receive
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. Receives: 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. Receives: 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
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.
Measured: 180 days
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.
Measured: 180 days
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.
Measured: 180 days
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.
Measured: baseline, day 180
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
Measured: 30 days, 60 days, 120 days, 180 days
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
Measured: 180 days
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.
Measured: baseline, day 180
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.
Measured: up to 270 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 May 201720 Oct 2020

First posted26 Sep 2016 (estimated)
Study start5 May 2017
Primary completion20 Oct 2020
Study completion20 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infantile HemangiomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 105 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02913612
Sponsor's protocol ID: Pro00068212
Acronym: TIM01
Status last verified: Mar 2024
First submitted: 12 Aug 2016
Last updated: 12 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 30790601

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)
ClinicalTrials.gov ID: NCT02913612
Acronym / sponsor ID: TIM01 / Pro00068212
Conditions: Infantile Hemangioma
Keywords: Hemangioma, Infantile Hemangioma, Pharmacokinetics
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 105 participants (actual)
Lead sponsor: Kanecia Obie ZimmermanUniversity, hospital or other
Collaborators: The Emmes Company, LLC, National Institutes of Health (NIH)
Study start: 5 May 2017 (actual)
Primary completion: 20 Oct 2020 (actual)
Study completion: 20 Oct 2020 (actual)
First posted: 26 Sep 2016 (estimated)
Results: Posted 15 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
0.25% Timolol Treatment	Experimental	Drug: 0.25% Timolol Maleate Gel Forming SolutionSubjects 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.
0.5% Timolol Treatment	Experimental	Drug: 0.5% Timolol Maleate Gel Forming SolutionSubjects 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.
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.

Who may qualify

Ages: Up to 84 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

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):

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
0.25% Timolol Maleate Gel Forming Solution50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution	Drug	0.25% Timolol Treatment
0.5% Timolol Maleate Gel Forming Solution50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution	Drug	0.5% Timolol Treatment

Primary outcome

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.

8 secondary outcomes

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
Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm
Time frame: 180 days
Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm
Time frame: 180 days
Change in Hemangioma Dynamic Complication Scale (HDCS)
Time frame: baseline, day 180
Number of Participants Who Reach Partial Response, Assessed by Volume
Time frame: 30 days, 60 days, 120 days, 180 days
Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color
Time frame: 180 days
Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants
Time frame: baseline, day 180
Number of Serious Adverse Events and Adverse Events of Special Interest in Infants Treated With Topical Timolol Maleate
Time frame: up to 270 days

Results and safety

Results posted to the registry on 15 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.25% Timolol Treatment	44	32
0.5% Timolol Treatment	51	33
Non-Intervention Group	10	7
Historical Controls	36	36

Primary outcome: 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. Count of participants. Unit: Participants

Measure	0.25% Timolol Treatment n = 44	0.5% Timolol Treatment n = 47	Non-Intervention Group n = 42
Value	24	28	15

0.5% Timolol Treatment vs Non-Intervention Group: Odds Ratio, log: 2.65 (95% CI 1.12 to 6.26), p = 0.0205, Fisher Exact
0.25% Timolol Treatment vs Non-Intervention Group: Odds Ratio, log: 2.16 (95% CI 0.91 to 5.14), p = 0.0619, Fisher Exact
0.25% Timolol Treatment vs 0.5% Timolol Treatment: Odds Ratio, log: 1.23 (95% CI 0.53 to 2.82), p = 0.6281, Fisher Exact

Population analysed: The Historical Control group was included with the Non-intervention group. Excludes 8 participants (four in the 0.5% dosage and four in the historical placebo controls) with out come determined to be unevaluable as they have no reported VAS scores

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Any event excluding adverse events of special interest beginning more than 7 days after the last dose of study drug or last study procedure will not be reported. For participants in the treatment arm adverse events of special interest only will be reviewed and reported at 90 days after the last dose of study drug.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0.25% Timolol Treatment	3 of 44 (6.8%)	31 of 44 (70.5%)	0 of 44
0.5% Timolol Treatment	2 of 51 (3.9%)	28 of 51 (54.9%)	0 of 51
Non-Intervention Group	0 of 10 (0%)	4 of 10 (40%)	0 of 10
Historical Controls	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 30790601Drolet 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kanecia Zimmerman, MD, MHS principal investigator

Duke Clinical Research Institute

Kristin Holland, MD study chair

Medical College of Wisconsin

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02913612, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.