Onreltea (Brimonidine) Gel In Pediatric Patients With Capillary Malformations

Onreltea (Brimonidine) Gel In Pediatric Patients With Capillary Malformations: A Prospective, Open-label, Cohort Study

Capillary Malformations (CM) affect a significant proportion of otherwise healthy children and may lead to psychological discomfort if left untreated. A significant proportion of untreated lesions undergo soft tissue thickening and darker discoloration later in life due to progressive ectasia of the affected vessels. While laser treatment is available, its use may be limited due to need for repeated sedation/general anesthetic use, partial response and cost.

The investigators propose to conduct an open-label, prospective, cohort study using Onreltea ( Brimonidine) gel for treatment of facial capillary malformations in children. The study medication will be applied topically on affected area of the skin daily for 12 weeks. Follow up visits will occur at at Week 1,4,8,12, and 16 to assess the efficacy and safety of the proposed treatment.

The study second aim is to explore the feasibility of conducting a multicenter placebo controlled study.

Study Overview

• Status: Terminated
• Conditions: Capillary Malformations
• Intervention / Treatment: Drug: Brimonidine 0.33% gel

Detailed Description

The investigators are planning to enroll in the study 20 participants at SickKids.

It is a prospective, open label, cohort study. Patients enrolled in the study will be followed at the Hospital For Sick Children for 16 weeks. They will come for the study visits 6 times: in 1 week, 4,8,12, and 16 weeks after the treatment has been started. During each study visit the study investigators will assess any changes in the characteristics of CM lesion(s) captured by a Chromometer *, Analogue Scale and Erythema Assessment tools. Participants or their parents will assess the changes at the final study visit (VAS and EA tools).

Patients will be provided with study medication for all duration of the study treatment (12 weeks).

The results of the treatment will be compared with the baseline data to evaluate the efficacy and safety of Onreltea (Brimonidine) gel in children with facial capillary malformations.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of facial capillary malformation (port-wine stain, PWS) made by a dermatologist
• age: 12-17 years of age
• weight > 45 kg
• lesions with a surface area < 100 cm2
• signed consent and assent for study participation

Exclusion Criteria:

• skin breakdown overlying the malformation due to other dermatological conditions (e.g. eczema, psoriasis)
• current or treatment with laser the past 3 months
• other topical treatments used within the past 4 weeks (e.g. rapamycin, corticosteroids, calcineurin inhibitors, etc)
• known chronic renal or hepatic disorders
• known cardiovascular disorders
• other systemic medications that potentially interact with Brimonidine (opiates, chlorpromazine, methyphenidate, reserpine, etc)
• mixed capillary/ venous or lymphatic malformations
• known allergy to one of the constituents of Onreltea
• pregnancy, or sexually active subjects of child-bearing potential (CBP), unwilling to use contraception during the study (such as barrier method, or oral contraceptives).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Onreltea ( Brimonidine); All the patients enrolled in the study will apply Onreltea ( Brimonidine 0.33%) gel on the affected skin area for 12 weeks (from Day 0 to Week 12 visit).	Drug: Brimonidine 0.33% gel; Topical application of Brimonidine 0.33% gel on Capillary Malformation (CM) lesion once daily for 12 weeks; Other Names: Onreltea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in the color of the capillary malformation using Chroma meter values (Δa, ΔE) at 12 weeks.	Measurement of erythema will be performed using Chroma Meter, CR-400, Konica, Minolta, Osaka, Japan. The meter readings will result in 3 values: L- refers to the relative light intensity, ranging from 0 (black) to +100 (white); a-captures color saturation, ranging from +60 (green) to -60 (red) and b- captures color spectrum from +60 (blue) to -60 (yellow). In most studies both, changes in a (Δa) and overall changes in the composite score (ΔE calculated as √((ΔL*before-ΔL*after)^2+(Δa*before-Δa*after)^2+(Δb*before-ΔL*after)^2 ) are obtained.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the color of the lesion (Δa, ΔE) at each follow up visit including the last visit at 16 weeks compared to baseline	Same as in primary outcome measure	1,4,8,16 weeks
Changes in CEA scores at 12, 16 weeks compared to baseline	A Clinician Erythema Assessment scale (CEA), consisting of a 0-4 numerical scale as follows: 0- clear skin, no erythema; almost clear skin, slight redness; mild erythema, definite redness; moderate erythema, marked redness; severe erythema, fiery redness	12 and 16 weeks
Changes in the iVAS at 12 and 16 weeks compared to baseline	Investigator's assessment of changes on the Visual Analogue Scale ( iVAS)	12 and 16 weeks
Correlation between iVAS, pVAS, CEA, pEA and Chroma Meter values	pVAS - patient/parent's Visual Analogue Scale assessment; pEA- patient/parent Erythema Assessment	1,4,8,12,16 weeks
Percentage of patients achieving 75% and 100% resolution of the lesion	by iVAS and chromo meter values	12 weeks
Frequency of observed and reported adverse events (AE)	AE documented in patient diary and mentioned at each study visit	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictors for a good response, defined as at least 50 % change in the erythema measured using Chroma Meter (a* after compared to a* before) at 12 weeks mark	Predictors for a good response, defined as at least 50 % change in the erythema measured using Chroma Meter (a* after compared to a* before) at 12 weeks mark. Percent of participants with predictors for a good response.	12 weeks
Percentage difference in Chroma Meter values (L -relative light intensity, a - color saturation, b - color spectrum) between treated and untreated lesions (control)	Changes in value ( e.g. "a") between baseline and Week *, calculated in % for investigational lesion, minus changes in value "a" between baseline and Week * , calculated in % for the control lesion. (a (inv.Week*) - a (inv. Baseline)/ a (inv. Baseline)) x 100% -- (a (contr. Week*) - a (contr. Baseline)/ a ( contr. baseline)) x 100%	1,4,8,12 and 16 weeks
Percentage of patients experiencing flare-up (defined as reoccurrence of the red discoloration) at the end of the study (16 weeks)	Percentage of patients experiencing flare-up (defined as reoccurrence of the red discoloration) at the end of the study (16 weeks)	16 weeks

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Galderma R&D

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 6, 2016

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: treatment; topical; Capillary malformations; Onrealtea; port-wine stain
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Vascular Malformations; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Brimonidine Tartrate
• Other Study ID Numbers: 1000051364

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No