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Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)

Primary Purpose

Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule

Status

Completed

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

NPC-12G gel

Placebo gel

About this trial

This is an interventional treatment trial for Tuberous Sclerosis focused on measuring Sirolimus, Skin lesions, TSC, Tuberous Sclerosis Complex, NPC-12G, Angiofibroma, Hypomelanotic macule, Plaque

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female patients 3 years old or greater at the time of informed consent
Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012)
Patients with three or more papules of angiofibroma ( >= 2 mm in diameter with redness in each) on the face at screening tests
Patients who are not suitable for therapy with laser or surgery, or who do not want therapy with laser or surgery
Patients or his/her guardian who give a written informed consent in understanding and willingness after having received enough explanation of the test drug and the current trial plan

Exclusion Criteria:

Patients who are hard to apply the test drug topically with keeping compliance
Patients with clinical findings such as erosion, ulcer and eruption on or around the lesion of angiofibroma, which may affect assessment of safety or efficacy
Patients who are hard to be taken pictures of their lesions adequately in such cases that they may not follow instruction of stillness
Patients with a history of hypersensitivity to alcohol or allergy to sirolimus
Patients who have complications such as malignant tumor, infection, serious heart disease, hepatic function disorder, renal function disorder or blood disorders which severity are considered by investigator as grade 2 or more severe with reference to ''Concerning classification criteria for seriousness of adverse drug reactions of medical agents''
Patients who have complications such as diseases unsuitable for the trial participation, for examples, uncontrolled diabetes (fasting blood glucose level >140 mg/dL or postprandial blood glucose level > 200 mg/dL), dyslipidemia (cholesterol level > 300 mg/dL or > 7.75 mmol/L, triglycerides level > 300 mg/dL or > 3.42 mmol/L), etc.
Patients who have taken drugs with mTOR inhibitory action including sirolimus, everolimus or temsirolimus within 12 months before the initial registration
Patients who have applied topical tacrolimus on the lesion of angiofibroma within 3 months before the initial registration
Patients who have received therapy with laser or surgery to the lesion of angiofibroma within 6 months before the initial registration
Female patients who may be pregnancy or are lactating
Patients who cannot agree to take appropriate measures of contraception until completion of post-treatment phase or follow-up period after discontinuation from informed consent
Patients who have participated in other clinical trial and have taken a trial drug within 6 months before the initial registration
Others, patients who are considered by the investigator as unsuitable for participation in the trial

Sites / Locations

Graduate School of Medicine, Osaka University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NPC-12G gel

Placebo gel

Arm Description

NPC-12G gel is containing 0.2% Sirolimus

Placebo gel is matched ingredient with NPC-12G gel

Outcomes

Primary Outcome Measures

Improvements in angiofibroma

Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee

Secondary Outcome Measures

Improvements in angiofibroma

Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee

Improvements in angiofibroma

Improvements comparing with baseline is assessed by the investigator

Improvements in redness of angiofibroma

Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator

Improvements in hypomelanotic macule and plaque of upper neck

Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator

The rate of patients who are evaluated as ''improvement'' or more (improvement rate) in primary outcome measure and in secondary outcome measures above outcome 1 to 5

Change in total score from baseline for DLQI and CDLQI

DLQI for subjects 16 years old and greater, or CDLQI for children of less than 16 years old is assessed by patients

Adverse events

Adverse events during the study period

Serious adverse events

Serious adverse events during the study period

Laboratory findings

Laboratory findings during the study period

Vital sign

Vital sign during the study period

Sirolimus blood concentration

Blood concentration of Sirolimus is assessed by drug monitoring

Full Information

NCT ID

NCT02635789

First Posted

December 15, 2015

Last Updated

February 1, 2017

Sponsor

Nobelpharma

1. Study Identification

Unique Protocol Identification Number

NCT02635789

Brief Title

Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)

Official Title

A Double-blind, Randomized, Placebo-controlled Phase III Trial to Investigate the Efficacy and Safety of NPC-12G Gel (Topical Formulation of Sirolimus) to Angiofibroma and Other Skin Lesions in Patients With Tuberous Sclerosis Complex

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

December 2015 (Actual)

Primary Completion Date

October 2016 (Actual)

Study Completion Date

October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nobelpharma

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this trial is to evaluate the efficacy and safety of NPC-12G gel (topical formulation of sirolimus) versus placebo gel to facial angiofibroma and other skin lesions in patients with tuberous sclerosis complex (TSC)

Detailed Description

Tuberous Sclerosis Complex (TSC) is an autosomal dominant hereditary disease that causes benign tumors on the almost whole body (including skin, brain, kidney, lung and heart), behavior disorder as autism, mental retardation and neurologic symptom as epilepsy. Angiofibroma is TSC-specific facial skin lesions, and hamartoma caused by increase of the component of skin connective tissues and blood vessels. Other skin lesions due to TSC are white macule(hypomelanotic macule), plaque, shagreen patch and ungual fibromas. Current therapeutic methods for angiofibroma are laser or surgical treatments, but there are problems as many relapses, deficiency of evidence, change of pigment, scar and risk of infection. This will be a multicenter, double-blind, randomized, placebo-controlled parallel group trial. The trial has three phases; the screening phase, double-blinded treatment phase, and post-treatment phase. The screening phase comprises a screening visit where subject's initial eligibility will be evaluated. During double-blinded treatment phase, patients who meet all entry criteria for the trial will be randomized into two groups, and they will apply 0.2% NPC-12G gel or placebo gel topically twice a day for 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule, Plaque

Keywords

Sirolimus, Skin lesions, TSC, Tuberous Sclerosis Complex, NPC-12G, Angiofibroma, Hypomelanotic macule, Plaque

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NPC-12G gel

Arm Type

Experimental

Arm Description

NPC-12G gel is containing 0.2% Sirolimus

Arm Title

Placebo gel

Arm Type

Placebo Comparator

Arm Description

Placebo gel is matched ingredient with NPC-12G gel

Intervention Type

Drug

Intervention Name(s)

NPC-12G gel

Intervention Description

NPC-12G gel is administered topically twice a day for 12 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo gel

Intervention Description

NPC-12G gel placebo is administered topically twice a day for 12 weeks

Primary Outcome Measure Information:

Title

Improvements in angiofibroma

Description

Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Improvements in angiofibroma

Description

Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee

Time Frame

Week 4 and 8 and follow-up Week 16

Title

Improvements in angiofibroma

Description

Improvements comparing with baseline is assessed by the investigator

Time Frame