Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis

Facial Angiofibroma Clinical Trial

Official title:

Study of Combination Therapy With Topical Rapamycin and Calcitriol for Cutaneous Lesions of Tuberous Sclerosis: A Double-blind Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03140449
• Other study ID #: 201306009MINB
• Status: Completed
• Phase: Phase 3
• First received: April 26, 2017
• Last updated: May 2, 2017
• Start date: September 5, 2013
• Est. completion date: April 25, 2017

Study information

• Verified date: September 2013
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to determine the effect and safety of topical rapamycin or calcitriol and their combination for the treatment of TSC-associated facial angiofibroma.

Methods: A total of 52 TSC patients including 20 male and 32 female subjects were recruited, and 50 of them completed the period 1 study. In period 1, topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. The primary end point was the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24). A follow-up FASI analysis for recurrence after drug discontinuance for 12 weeks was also performed (week 36). The secondary end point was the reduction of Visual Analysis Score (VAS) evaluated by the subjects themselves at week 12.

Description:

Background: Tuberous sclerosis complex (TSC)-associated facial angiofibroma is psychologically debilitating to both patients and their family members. The pathogenesis of TSC stems from TSC1 or TSC2 mutations, leading to the defect in mechanistic target of rapamycin (mTOR) inhibition. Rapamycin is an mTOR inhibitor and is effective for TSC facial angiofibroma through topical administration. Calcitriol, a vitamin D3 analogue, has been shown to lessen skin fibrosis in scleroderma and may be therapeutically beneficial to angiofibromas.

Objectives: The aim of the study is to determine the effect and safety of topical rapamycin or calcitriol and their combination for the treatment of TSC-associated facial angiofibroma.

Methods: A total of 52 TSC patients including 20 male and 32 female subjects were recruited, and 50 of them completed the period 1 study. In period 1, topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. The primary end point was the reduction of facial angiofibroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24). A follow-up FASI analysis for recurrence after drug discontinuance for 12 weeks was also performed (week 36). The secondary end point was the reduction of Visual Analysis Score (VAS) evaluated by the subjects themselves at week 12.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: April 25, 2017
• Est. primary completion date: November 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Subjects must have been diagnosed or highly suspected as having TSC.

2. Subjects must be aged 7 to 70 years at Screening, and can be either sex.

3. Subjects must have symmetric facial angiofibromas.

Exclusion Criteria:

1. Pregnancy or with a plan to be pregnant.

2. Subjects who cannot comply the treatment protocol.

3. Subjects with kidney or liver/ biliary dysfunction.

4. Subjects with hypercalcaemia and patients known to suffer from abnormal calcium metabolism.

5. Subjects on systemic treatment of calcium deficiency.

6. Subjects known to be hypersensitive to rapamycin or calcitriol.

Related Conditions & MeSH terms

• Angiofibroma
• Facial Angiofibroma
• Sclerosis
• Tuberous Sclerosis

Intervention

Drug:
• Rapamycin
topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24).
• Calcitriol
topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24).
• Rapamycin-calcitriol combination
topical rapamycin (0.1%) or calcitriol (3 mcg/g) single-agent therapy versus their combination were applied twice a day by a left-right randomized, split-face comparison for 12 weeks. In period 2, the patients entered an open-label study and were reassigned to use the more effective ointment on both cheeks for another 12 weeks (week 13-24).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	facial angio?broma severity index (FASI)	the reduction of facial angio?broma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12	at week 12