Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Sclerosis

Facies

Tuberous Sclerosis

Angiofibroma

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Tuberous Sclerosis Complex

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Bone Density Conservation Agents

Micronutrients

Vasoconstrictor Agents

Sirolimus

Calcitriol

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

Hormones

Calcium

Calcium, Dietary

Vitamins

Trace Elements

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

Rapamycin-calcitriol combination

YI-HUA LIAO, A.P.

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.

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.

Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis

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

the reduction of facial angioﬁbroma severity index (FASI) for the grade of erythema, papule size, elevation and extension of the lesions at week 12

National Taiwan University Hospital

Blood and Lymph Conditions

Immune System Diseases

Lymphangioleiomyomatosis

Fibroma

Astrocytoma

Angiomyolipoma

Rhabdomyoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Lymphangiomyoma

Perivascular Epithelioid Cell Neoplasms

Neoplasms, Connective and Soft Tissue

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Adipose Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Myoma

Subependymal Giant Cell Astrocytoma

Neuroepithelioma

Üarticipants diagnosed with Tuberous Sclerosis Complex (TSC) aged between 2 months and 50 years.

Peter Bauer, Prof.Dr

International, multicenter, observational, longitudinal study to identify biomarker/s for Tuberous Sclerosis Complex and to explore the clinical robustness, specificity, and long´-term variability of these biomarker/s

Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by the growth of numerous tumors in different body parts related to dysregulation of the mechanistic target of rapamycin (mTOR) pathway. The overall incidence of TSC is estimated to be as high as 1 in 6000 to 10,000 live birth.The main aspects of TSC that influence the quality of life are associated with the brain: seizures, evelopmental delay, intellectual disability, and autism. However, the incidence and severity of the various aspects of TSC can vary widely.

TSC is generally caused by pathogenic variants in the tumor suppressor genes: TSC1 and TSC2. Confirmation of a clinical diagnosis of tuberous sclerosis is performed via TSC1 and TSC2 sequencing.

There is no cure for TSC, therefore symptomatic therapy is the best possible choice, including mTOR inhibitors, vigabatrin and other antiepileptic drugs for the seizures, and neurosurgery in cases of life-threatening neurological symptoms.

The aim of the study is established TSC specific biomarker/s. Such biomarkers aim to facilitate the diagnosis, treatment personalization and monitoring.

Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)

Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)

Biomarkers for Tuberous Sclerosis Complex: An International Multicenter Observational Longitudinal Protocol

All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

Samples will be analyzed for the candidate biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

CENTOGENE GmbH Rostock

Disease Attributes

Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

Placebo cream topical, applied once daily before bed on affected area for 26 weeks

Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

rapamycin

placebo

Ioana Stanescu

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).

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).

Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex

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

Individual Participant Data is not planned to be shared with other researchers

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

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

1. Almost Clear
2. Mild
3. Moderate
4. Severe

The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.

IGA scores range from 0-4:

0=Clear

1. Almost Clear
2. Mild
3. Moderate
4. Severe

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

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.

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.

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.

Dermatology Specialties Limited Partnership

Adverse events were collected during each clinical visit and follow-up visit. Patients or their parents/guardians were questioned by the investigator regarding any adverse events experienced since the previous clinical visit.

Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

0.5% Rapamycin Cream, Topical

Rapamycin cream topical, 1.0% w/w, applied once daily before bed on affected area for 26 weeks

rapamycin: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

1.0% Rapamycin Cream, Topical

Placebo cream topical, applied once daily before bed on affected area for 26 weeks

placebo: Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

Placebo

Total

Age, Continuous

Age group

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Site

Height

Weight

Rapamycin concentration

The Investigator's Global Assessment (IGA) measures the severity of facial angiofibroma, with scores between 0 (clear) and 4 (severe).

0 = Clear

1. = Almost Clear
2. = Mild
3. = Moderate
4. = Severe

Investigator's Global Assessment (IGA)

Facial Angiofibroma Severity Index (FASI) grades lesions according to their erythema, size and extent. Scores range between 2 and 9. Scores are summed from the following measures:

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

Facial Angiofibroma Severity Index (FASI)

Covid-19 pandemic halted recruitment, leading to a smaller number of patients recruited than intended (107/120).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis	NCT03140449	Facial Angiofib...	Rapamycin Calcitriol Rapamycin-calci...	7 Years - 65 Years	National Taiwan University Hospital
Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)	NCT02654340	Hypomelanotic M... Facial Angiofib... Shagreen Patche... Ungual Fibromas Cortical Dyspla... Cardiac Rhabdom... Lymphangioleiom... Renal Angiomyol... Subependymal Gi...		2 Years - 50 Years	CENTOGENE GmbH Rostock
Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex	NCT03826628	Facial Angiofib... Tuberous Sclero...	rapamycin placebo	6 Years - 65 Years	Dermatology Specialties Limited Partnership
Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)	NCT02654340	Hypomelanotic M... Facial Angiofib... Shagreen Patche... Ungual Fibromas Cortical Dyspla... Cardiac Rhabdom... Lymphangioleiom... Renal Angiomyol... Subependymal Gi...		2 Years - 50 Years	CENTOGENE GmbH Rostock
Topical Rapamycin and Calcitriol for Angiofibroma of Tuberous Sclerosis	NCT03140449	Facial Angiofib...	Rapamycin Calcitriol Rapamycin-calci...	7 Years - 65 Years	National Taiwan University Hospital
Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)	NCT02654340	Hypomelanotic M... Facial Angiofib... Shagreen Patche... Ungual Fibromas Cortical Dyspla... Cardiac Rhabdom... Lymphangioleiom... Renal Angiomyol... Subependymal Gi...		2 Years - 50 Years	CENTOGENE GmbH Rostock

Spots Global Cancer Trial Database for facial angiofibroma