Facial AngiofibromaPhase 2/3NCT03826628
Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex
A Phase 2/3 study testing rapamycin in people with Facial Angiofibroma and Tuberous Sclerosis, run by Dermatology Specialties Limited Partnership at 17 sites in 9 countries.
Trial summary
The study aims to compare the safety and efficacy of two different strengths of Rapamycin cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA) associated with Tuberous Sclerosis Complex (TSC). Read more about this study
- Who is it for?
- Ages 6 to 65 years
- Conditions the study is for
- Facial Angiofibroma, Tuberous Sclerosis
- What is being tested?
- rapamycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 17 sitesin 9 countries
- Study dates
- 28 Jul 2019to 1 Sep 2022
- Phase
- Phase 2/3
- 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 6 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is obtained
- Patients diagnosed with TSC based on the clinical diagnostic criteria of International Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial angiofibroma
- An FA severity score of 2 or 3 on the IGA scale
- Patients or their legal representatives capable of understanding the explanation of the clinical trial and who give written informed consent for participation
- Patients or their legal representatives able to maintain patient diaries following the instructions of the investigator or sub-investigator
Who cannot join
- Patients who cannot carry out the treatment plan or follow-up assessment
- Patients with serious skin lesions such as erosions or ulcers
- Patients with known hypersensitivity to any component of the study product
- Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment
- Patients who received laser therapy or surgical therapy within 6 months prior to trial enrolment
- Patients who participated in any other clinical trial within 3 months prior to the day of enrolment
Show all 12Show fewer
- Patients judged unsuitable for this clinical trial by the investigator or sub-investigator
- Pregnant or lactating females
- Sexually active females of childbearing potential not using adequate contraception and sexually active males not using adequate contraception
- Patients with immune dysfunction or receiving any form of immunosuppression
- Patients with severe FA, with a score of 4 on the IGA scale
- Patients with an FA severity score of less than 2 on the IGA scale
Trial locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
United States6 sites
University of Virginia
Charlottesville, Virginia, 22903
Spectrum Health
Grand Rapids, Michigan, 49503
University of California San Diego
La Jolla, California, 92037
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Mayo Clinic
Rochester, Minnesota, 55905
All Children's Research Institute
St. Petersburg, Florida, 33701
Hungary2 sites
Bethesda Children's Hospital of the Hungarian Reformed Church
Budapest, G39Q+49
University of Pécs
Pécs, H-7624
Serbia2 sites
Clinic of Neurology and Psychiatry for Children and Youth
Belgrade, 11000
Clinical Center of Serbia
Belgrade, 11000
Spain2 sites
Clínica Universidad de Navarra
Madrid, 28007
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
New Zealand1 site
Canterbury District Health Board
Christchurch, Canterbury, 8011
About this study
Official title: A Phase 2/3, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Dose-Response Comparison of the Efficacy and Safety of a Topical Rapamycin Cream for the Treatment of Facial Angiofibromas (FA) Associated With Tuberous Sclerosis Complex (TSC) in Patients 6 Years of Age and Over
The study aims to compare the safety and efficacy of two different strengths of Rapamycin cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA) associated with Tuberous Sclerosis Complex (TSC).
Read the detailed description
Topical rapamycin has previously been used to treat FA associated with TSC, reducing erythema, papule size, while flattening lesions and improving skin texture. Topical rapamycin has been reported to be well tolerated.
The efficacy and safety of a topical rapamycin cream at two strengths (0.5% and 1.0%) will be assessed during a 26 week double-blind treatment phase with assessments made at clinical visits at baseline, 2, 8, 14, 20 and 26 weeks, and at follow-up (4 weeks after the last dose of study drug).
- Conditions
- Facial Angiofibroma, Tuberous Sclerosis
- Being tested
- rapamycin, placebo
- Medical subject headings
- Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rapamycinDrug
Also called sirolimus
Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
placeboDrug
Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| 0.5% Rapamycin cream, topical | Experimental | Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks Receives: Drug: rapamycin |
| 1.0% Rapamycin cream, topical | Experimental | Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks Receives: Drug: rapamycin |
| Placebo | Placebo comparator | Placebo cream topical, applied once daily before bed on affected area for 26 weeks Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Obtaining Successful Treatment
Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:
0=Clear
- Almost Clear
- Mild
- Moderate
- Severe
Measured: After 26 weeks treatment
Secondary outcomes (6)
Time to Treatment Success
The time elapsed from the first dose to the time of treatment success, according to the Investigator's Global Assessment (IGA) scale. The total time of treatment was 26 weeks, although Covid-19 visit delays led to an extension of up to 2 weeks (28 weeks total) for some patients. Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4:
0=Clear
- Almost Clear
- Mild
- Moderate
- Severe
Measured: From first dose to 26 weeks (± 2 weeks)
Change From Baseline in Investigator's Global Assessment
The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.
IGA scores range from 0-4:
0=Clear
- Almost Clear
- Mild
- Moderate
- Severe
Measured: At baseline and after 26 weeks treatment
Change From Baseline in Facial Angiofibroma Severity Index (FASI)
The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline. FASI grades lesions according to their erythema, size and extent by summing the scores of each category. The final FASI scores range from (mild) 2-9 (severe).
Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (< 5mm) 1 Large (> 5mm) 2 Confluent 3 Extension <50 % cheek surface 2 >50% cheek surface 3
Measured: At baseline and after 26 weeks treatment
Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale
Percentage change in facial angiofibroma since beginning treatment, as assessed by the participant or parent/caregiver. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where the participant or parent/caregiver estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.
Measured: After 26 weeks treatment
Objective (Clinician) Percentage Change Rating Scale
Percentage improvement in facial angiofibroma since beginning treatment, as assessed by the clinician. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where clinicians estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.
Measured: After 26 weeks treatment
Categorical Change in Facial Angiofibroma
Change in facial angiofibroma since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver. This was a single assessment time-point, where the participant or parent/caregiver evaluated the change in the facial angiofibroma lesion appearance from their perspective since baseline.
Measured: After 26 weeks treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start28 Jul 2019
- Primary completion1 Sep 2022
- Study completion1 Sep 2022
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 Facial AngiofibromaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dermatology Specialties Limited Partnership
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ioana Stanescu, Study director, Dermatology Specialties Limited Partnership
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03826628
- Sponsor's protocol ID
- DSLP-01
- Status last verified
- Jul 2022
- First submitted
- 29 Jan 2019
- Last updated
- 8 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data is not planned to be shared with other researchers
Publications
Aitken P, Stanescu I, Boddington L, Mahon C, Fogarasi A, Liao YH, Ivars M, Moreno-Artero E, Trauner D, DeRoos ST, Jancic J, Nikolic M, Balazova P, Price HN, Hadzsiev K, Riney K, Stapleton S, Tollefson MM, Bauer D, Pinkova B, Atkinson H. A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial. Br J Dermatol. 2023 Oct 25;189(5):520-530. doi: 10.1093/bjd/ljad243.
PubMed 37463422
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Dose-Response Comparison of the Efficacy and Safety of a Topical Rapamycin Cream for the Treatment of Facial Angiofibromas (FA) Associated With Tuberous Sclerosis Complex (TSC) in Patients 6 Years of Age and Over
- ClinicalTrials.gov ID
- NCT03826628
- Acronym / sponsor ID
- DSLP-01
- Conditions
- Facial Angiofibroma, Tuberous Sclerosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Dermatology Specialties Limited PartnershipIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2019 (actual)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 1 Feb 2019 (actual)
- Results
- Posted 14 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims to compare the safety and efficacy of two different strengths of Rapamycin cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA) associated with Tuberous Sclerosis Complex (TSC).
Detailed description
Topical rapamycin has previously been used to treat FA associated with TSC, reducing erythema, papule size, while flattening lesions and improving skin texture. Topical rapamycin has been reported to be well tolerated.
The efficacy and safety of a topical rapamycin cream at two strengths (0.5% and 1.0%) will be assessed during a 26 week double-blind treatment phase with assessments made at clinical visits at baseline, 2, 8, 14, 20 and 26 weeks, and at follow-up (4 weeks after the last dose of study drug).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 0.5% Rapamycin cream, topical | Experimental | Drug: rapamycinRapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks |
| 1.0% Rapamycin cream, topical | Experimental | Drug: rapamycinRapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks |
| Placebo | Placebo comparator | Drug: placeboPlacebo cream topical, applied once daily before bed on affected area for 26 weeks |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is obtained
- Patients diagnosed with TSC based on the clinical diagnostic criteria of International Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial angiofibroma
- An FA severity score of 2 or 3 on the IGA scale
- Patients or their legal representatives capable of understanding the explanation of the clinical trial and who give written informed consent for participation
- Patients or their legal representatives able to maintain patient diaries following the instructions of the investigator or sub-investigator
Key exclusion criteria (12 listed)
- Patients who cannot carry out the treatment plan or follow-up assessment
- Patients with serious skin lesions such as erosions or ulcers
- Patients with known hypersensitivity to any component of the study product
- Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment
- Patients who received laser therapy or surgical therapy within 6 months prior to trial enrolment
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 |
|---|---|---|
| rapamycinAlso: sirolimusApply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks | Drug | 0.5% Rapamycin cream, topical, 1.0% Rapamycin cream, topical |
| placeboApply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks | Drug | Placebo |
Primary outcome
Percentage of Participants Obtaining Successful Treatment
Time frame: After 26 weeks treatment
Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4: 0=Clear 1. Almost Clear 2. Mild 3. Moderate 4. Severe
6 secondary outcomes
Time to Treatment Success
Time frame: From first dose to 26 weeks (± 2 weeks)
Change From Baseline in Investigator's Global Assessment
Time frame: At baseline and after 26 weeks treatment
Change From Baseline in Facial Angiofibroma Severity Index (FASI)
Time frame: At baseline and after 26 weeks treatment
Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale
Time frame: After 26 weeks treatment
Objective (Clinician) Percentage Change Rating Scale
Time frame: After 26 weeks treatment
Categorical Change in Facial Angiofibroma
Time frame: After 26 weeks treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37463422Aitken P, Stanescu I, Boddington L, Mahon C, Fogarasi A, Liao YH, Ivars M, Moreno-Artero E, Trauner D, DeRoos ST, Jancic J, Nikolic M, Balazova P, Price HN, Hadzsiev K, Riney K, Stapleton S, Tollefson MM, Bauer D, Pinkova B, Atkinson H. A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial. Br J Dermatol. 2023 Oct 25;189(5):520-530. doi: 10.1093/bjd/ljad243.
- Individual participant dataSharing planned: No. Individual Participant Data is not planned to be shared with other researchers
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.
Ioana Stanescu study director
Dermatology Specialties Limited Partnership
17 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing rapamycin in people with Facial Angiofibroma and Tuberous Sclerosis, run by Dermatology Specialties Limited Partnership at 17 sites in 9 countries.
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 5 inclusion and 12 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 8 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Hungary, Serbia, Spain, Australia and 4 more countries. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 14 Aug 2023). 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?
Percentage of Participants Obtaining Successful Treatment (time frame: After 26 weeks treatment). 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 NCT03826628, 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 8 Sep 2023.