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

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ClinicalTrials.gov Identifier: NCT02635789
Recruitment Status : Completed
First Posted : December 21, 2015
Last Update Posted : February 2, 2017
Sponsor:
Information provided by (Responsible Party):
Nobelpharma

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)

Condition or disease Intervention/treatment Phase
Tuberous Sclerosis Angiofibroma Hypomelanotic Macule Plaque Drug: NPC-12G gel Drug: Placebo gel Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 2015
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016


Arm Intervention/treatment
Experimental: NPC-12G gel
NPC-12G gel is containing 0.2% Sirolimus
Drug: NPC-12G gel
NPC-12G gel is administered topically twice a day for 12 weeks

Placebo Comparator: Placebo gel
Placebo gel is matched ingredient with NPC-12G gel
Drug: Placebo gel
NPC-12G gel placebo is administered topically twice a day for 12 weeks




Primary Outcome Measures :
  1. Improvements in angiofibroma [ Time Frame: 12 weeks ]
    Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee


Secondary Outcome Measures :
  1. Improvements in angiofibroma [ Time Frame: Week 4 and 8 and follow-up Week 16 ]
    Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee

  2. Improvements in angiofibroma [ Time Frame: Week 4, 8, 12 and follow-up Week 16 ]
    Improvements comparing with baseline is assessed by the investigator

  3. Improvements in redness of angiofibroma [ Time Frame: Week 4, 8, 12 and follow-up Week 16 ]
    Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator

  4. Improvements in hypomelanotic macule and plaque of upper neck [ Time Frame: Week 4, 8, 12 and follow-up Week 16 ]
    Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator

  5. 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 [ Time Frame: Week 4, 8, 12 and follow-up Week 16 ]
  6. Change in total score from baseline for DLQI and CDLQI [ Time Frame: Week 4, 8, 12 and follow-up Week 16 ]
    DLQI for subjects 16 years old and greater, or CDLQI for children of less than 16 years old is assessed by patients

  7. Adverse events [ Time Frame: 16 weeks ]
    Adverse events during the study period

  8. Serious adverse events [ Time Frame: 16 weeks ]
    Serious adverse events during the study period

  9. Laboratory findings [ Time Frame: 16 weeks ]
    Laboratory findings during the study period

  10. Vital sign [ Time Frame: 16 weeks ]
    Vital sign during the study period

  11. Sirolimus blood concentration [ Time Frame: Baseline, Week 4 and Week 12 ]
    Blood concentration of Sirolimus is assessed by drug monitoring



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients 3 years old or greater at the time of informed consent
  2. Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012)
  3. Patients with three or more papules of angiofibroma ( >= 2 mm in diameter with redness in each) on the face at screening tests
  4. Patients who are not suitable for therapy with laser or surgery, or who do not want therapy with laser or surgery
  5. 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:

  1. Patients who are hard to apply the test drug topically with keeping compliance
  2. 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
  3. Patients who are hard to be taken pictures of their lesions adequately in such cases that they may not follow instruction of stillness
  4. Patients with a history of hypersensitivity to alcohol or allergy to sirolimus
  5. 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''
  6. 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.
  7. Patients who have taken drugs with mTOR inhibitory action including sirolimus, everolimus or temsirolimus within 12 months before the initial registration
  8. Patients who have applied topical tacrolimus on the lesion of angiofibroma within 3 months before the initial registration
  9. Patients who have received therapy with laser or surgery to the lesion of angiofibroma within 6 months before the initial registration
  10. Female patients who may be pregnancy or are lactating
  11. 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
  12. Patients who have participated in other clinical trial and have taken a trial drug within 6 months before the initial registration
  13. Others, patients who are considered by the investigator as unsuitable for participation in the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02635789


Locations
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Japan
Graduate School of Medicine, Osaka University
Suita, Osaka, Japan, 565-0871
Sponsors and Collaborators
Nobelpharma
Investigators
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Principal Investigator: Mari Wataya-Kaneda, MD, PhD Department of Dermatology, Graduate School of Medicine, Osaka University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nobelpharma
ClinicalTrials.gov Identifier: NCT02635789    
Other Study ID Numbers: NPC-12G-1
First Posted: December 21, 2015    Key Record Dates
Last Update Posted: February 2, 2017
Last Verified: February 2017
Keywords provided by Nobelpharma:
Sirolimus
Skin lesions
TSC
Tuberous Sclerosis Complex
NPC-12G
Angiofibroma
Hypomelanotic macule
Plaque
Additional relevant MeSH terms:
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Tuberous Sclerosis
Angiofibroma
Sclerosis
Pathologic Processes
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type