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

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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

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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Improvements in angiofibroma

Secondary Outcome

 Improvements in angiofibroma

Condition

Tuberous Sclerosis

Intervention

NPC-12G gel

Study Arms / Comparison Groups

 NPC-12G gel
Description:  NPC-12G gel is containing 0.2% Sirolimus

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

62

Start Date

December 2015

Completion Date

October 2016

Primary Completion Date

October 2016

Eligibility 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
      

Gender

All

Ages

3 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mari Wataya-Kaneda, MD, PhD, , 

Location Countries

Japan

Location Countries

Japan

Administrative Informations


NCT ID

NCT02635789

Organization ID

NPC-12G-1


Responsible Party

Sponsor

Study Sponsor

Nobelpharma


Study Sponsor

Mari Wataya-Kaneda, MD, PhD, Principal Investigator, Department of Dermatology, Graduate School of Medicine, Osaka University


Verification Date

February 2017