Dose-Ranging Efficacy and Safety Study of Topical Rapamyc... | NCT03826628

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
0.5% Rapamycin cream, topical	Experimental	Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks	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	Drug: rapamycin
Placebo	Placebo Comparator	Placebo cream topical, applied once daily before bed on affected area for 26 weeks	Drug: placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
rapamycin	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	After 26 weeks treatment

Secondary Outcomes

Measure	Description	Time Frame
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

Eligibility Module

Name	Affiliation	Role
Ioana Stanescu	Dermatology Specialties Limited Partnership	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Phoenix Children's Hospital		Phoenix	Arizona	85016	United States
University of California San Diego

PubMed Identifier	Type	Citation	Retractions
37463422	Result	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	0.5% Rapamycin Cream, Topical	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
FG001	1.0% Rapamycin Cream, Topical

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 1, 2021

Arm/Group Information

ID	Title	Description
BG000	0.5% Rapamycin Cream, Topical	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
BG001	1.0% 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
BG002	Placebo	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
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00036 BG00133 BG00238 BG003107

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00027.8± 15 BG00125.5± 15 BG00226.3± 13.8 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Age group

Title	Measurements
6-11 years	BG0006 BG0014 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00021 BG00114 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0005 BG0014 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

Study Site

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Site #00 - ACRI Johns Hopkins	BG0000 BG0010 BG002

Height

Mean

Standard Deviation

centimeters

Title

Denominators

Categories

Title	Measurements
	BG000164± 17 BG001165± 16 BG002

Weight

Mean

Standard Deviation

kilograms

Title

Denominators

Categories

Title	Measurements
	BG00068.1± 22.8 BG00168.9± 24.3 BG002

BMI

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00024.7± 5.6 BG00124.8± 6.6 BG002

Rapamycin concentration

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Below limit of detection	BG00036 BG00133 BG002

Investigator's Global Assessment (IGA)

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

0 = Clear

= Almost Clear
= Mild
= Moderate
= Severe

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
2 - Mild	BG00013 BG001

Facial Angiofibroma Severity Index (FASI)

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

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
4	BG0007 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Posted

Count of Participants

Participants

After 26 weeks treatment

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Units	Counts
Participants	OG00036 OG00133 OG00238

Title

Denominators

Categories

Title	Measurements
	OG0004 OG0013 OG0022

Secondary

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

Posted

Mean

Standard Error

weeks

From first dose to 26 weeks (± 2 weeks)

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Secondary

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

Posted

Count of Participants

Participants

At baseline and after 26 weeks treatment

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Secondary

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

Posted

Count of Participants

Participants

At baseline and after 26 weeks treatment

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Secondary

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.

Posted

Mean

Standard Error

Percentage Change

After 26 weeks treatment

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Secondary

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.

Posted

Mean

Standard Error

Percentage Change

After 26 weeks treatment

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Secondary

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.

Posted

Count of Participants

Participants

After 26 weeks treatment

ID	Title	Description
OG000	0.5% Rapamycin Cream, Topical	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
OG001	1.0% 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
OG002	Placebo	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

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	0.5% Rapamycin Cream, Topical	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	36	2	36	29	36
EG001	1.0% 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	33	2	33	27	33
EG002	Placebo	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	38	2	38	27	38

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Seizure	Nervous system disorders	MedDRA (24.0)	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected33 at risk EG0022 events1 affected38 at risk
Constipation, nausea, malnutrition, diarrhea	Gastrointestinal disorders	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected33 at risk EG0022 events2 affected38 at risk
Chest pain	Cardiac disorders	MedDRA (24.0)	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected33 at risk EG0020 events0 affected38 at risk
Kidney bleeding	Renal and urinary disorders	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected33 at risk EG0020 events0 affected38 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected33 at risk EG0021 events1 affected38 at risk
Collapsed lung	Injury, poisoning and procedural complications	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected33 at risk EG0020 events0 affected38 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Skin burning sensation	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG00015 events13 affected36 at risk EG0017 events6 affected33 at risk EG0025 events5 affected38 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0009 events9 affected36 at risk EG00113 events12 affected33 at risk EG0022 events2 affected38 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0007 events7 affected36 at risk EG0017 events6 affected33 at risk EG0025 events4 affected38 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0007 events7 affected36 at risk EG0015 events5 affected33 at risk EG0020 events0 affected38 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0003 events3 affected36 at risk EG0014 events4 affected33 at risk EG0022 events2 affected38 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0004 events2 affected36 at risk EG0013 events3 affected33 at risk EG0022 events2 affected38 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected33 at risk EG0020 events0 affected38 at risk
Skin haemorrhage	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0004 events2 affected36 at risk EG0010 events0 affected33 at risk EG0022 events1 affected38 at risk
Skin tightness	Skin and subcutaneous tissue disorders	MedDRA (24.0)	Systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected33 at risk EG0020 events0 affected38 at risk
Folliculitis	Infections and infestations	MedDRA (24.0)	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected33 at risk EG0022 events2 affected38 at risk
Nasopharyngitis	Infections and infestations	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected33 at risk EG0022 events2 affected38 at risk
Rhinitis	Infections and infestations	MedDRA (24.0)	Systematic Assessment	EG0001 events1 affected36 at risk EG0012 events2 affected33 at risk EG0020 events0 affected38 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected33 at risk EG0023 events3 affected38 at risk
Influenza	Infections and infestations	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected33 at risk EG0022 events2 affected38 at risk
Urinary tract infection	Infections and infestations	MedDRA (24.0)	Systematic Assessment	EG0004 events2 affected36 at risk EG0010 events0 affected33 at risk EG0020 events0 affected38 at risk
Seizure	Nervous system disorders	MedDRA (24.0)	Systematic Assessment	EG0002 events2 affected36 at risk EG0015 events4 affected33 at risk EG0020 events0 affected38 at risk
Paraesthesia	Nervous system disorders	MedDRA (24.0)	Systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected33 at risk EG0021 events1 affected38 at risk
Headache	Nervous system disorders	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected33 at risk EG0023 events2 affected38 at risk
Fatigue	General disorders	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0012 events1 affected33 at risk EG0023 events2 affected38 at risk
Pyrexia	General disorders	MedDRA (24.0)	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected33 at risk EG0023 events2 affected38 at risk
Haemorrhage	Vascular disorders	MedDRA (24.0)	Systematic Assessment	EG0002 events2 affected36 at risk EG0015 events3 affected33 at risk EG0022 events2 affected38 at risk
Nausea	Gastrointestinal disorders	MedDRA (24.0)	Systematic Assessment	EG0002 events1 affected36 at risk EG0010 events0 affected33 at risk EG0022 events2 affected38 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (24.0)	Systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected33 at risk EG0022 events2 affected38 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.0)	Systematic Assessment	EG0002 events1 affected36 at risk EG0010 events0 affected33 at risk EG0024 events2 affected38 at risk

ID	Term
D006222	Hamartoma
D009369	Neoplasms
D009378	Neoplasms, Multiple Primary
D009386	Neoplastic Syndromes, Hereditary
D065703	Malformations of Cortical Development, Group I
D054220	Malformations of Cortical Development
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020752	Neurocutaneous Syndromes
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn

ID	Term
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals