Tuberous SclerosisPhase 3NCT02635789
Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)
A Phase 3 study testing NPC-12G gel in people with Tuberous Sclerosis and Angiofibroma, run by Nobelpharma at 1 site in Japan.
Trial 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) Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule
- What is being tested?
- NPC-12G gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteJapan
- Study dates
- Dec 2015to Oct 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Japan1 site
Graduate School of Medicine, Osaka University
Suita, Osaka, 565-0871
About this study
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
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)
Read the 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.
- Conditions
- Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule, Plaque
- Being tested
- NPC-12G gel, Placebo gel
- Keywords
- Sirolimus, Skin lesions, TSC, Tuberous Sclerosis Complex, NPC-12G, Angiofibroma, Hypomelanotic macule, Plaque
- Medical subject headings
- Tuberous Sclerosis, Angiofibroma, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPC-12G gelDrug
NPC-12G gel is administered topically twice a day for 12 weeks
Placebo gelDrug
NPC-12G gel placebo is administered topically twice a day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| NPC-12G gel | Experimental | NPC-12G gel is containing 0.2% Sirolimus Receives: Drug: NPC-12G gel |
| Placebo gel | Placebo comparator | Placebo gel is matched ingredient with NPC-12G gel Receives: Drug: Placebo gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvements in angiofibroma
Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee
Measured: 12 weeks
Secondary outcomes (11)
Improvements in angiofibroma
Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee
Measured: Week 4 and 8 and follow-up Week 16
Improvements in angiofibroma
Improvements comparing with baseline is assessed by the investigator
Measured: Week 4, 8, 12 and follow-up Week 16
Improvements in redness of angiofibroma
Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator
Measured: Week 4, 8, 12 and follow-up Week 16
Improvements in hypomelanotic macule and plaque of upper neck
Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator
Measured: Week 4, 8, 12 and follow-up Week 16
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
Measured: Week 4, 8, 12 and follow-up Week 16
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
Measured: Week 4, 8, 12 and follow-up Week 16
Adverse events
Adverse events during the study period
Measured: 16 weeks
Serious adverse events
Serious adverse events during the study period
Measured: 16 weeks
Laboratory findings
Laboratory findings during the study period
Measured: 16 weeks
Vital sign
Vital sign during the study period
Measured: 16 weeks
Sirolimus blood concentration
Blood concentration of Sirolimus is assessed by drug monitoring
Measured: Baseline, Week 4 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberous SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nobelpharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mari Wataya-Kaneda, MD, PhD, Principal investigator, Department of Dermatology, Graduate School of Medicine, Osaka University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02635789
- Sponsor's protocol ID
- NPC-12G-1
- Status last verified
- Feb 2017
- First submitted
- 15 Dec 2015
- Last updated
- 2 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Wataya-Kaneda M, Ohno Y, Fujita Y, Yokozeki H, Niizeki H, Ogai M, Fukai K, Nagai H, Yoshida Y, Hamada I, Hio T, Shimizu K, Murota H. Sirolimus Gel Treatment vs Placebo for Facial Angiofibromas in Patients With Tuberous Sclerosis Complex: A Randomized Clinical Trial. JAMA Dermatol. 2018 Jul 1;154(7):781-788. doi: 10.1001/jamadermatol.2018.1408.
PubMed 29800026
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02635789
- Acronym / sponsor ID
- NPC-12G-1
- Conditions
- Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule, Plaque
- Keywords
- Sirolimus, Skin lesions, TSC, Tuberous Sclerosis Complex, NPC-12G, Angiofibroma, Hypomelanotic macule, Plaque
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- NobelpharmaIndustry (pharma, biotech, devices)
- Study start
- Dec 2015 (actual)
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 21 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NPC-12G gel | Experimental | Drug: NPC-12G gelNPC-12G gel is containing 0.2% Sirolimus |
| Placebo gel | Placebo comparator | Drug: Placebo gelPlacebo gel is matched ingredient with NPC-12G gel |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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''
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NPC-12G gelNPC-12G gel is administered topically twice a day for 12 weeks | Drug | NPC-12G gel |
| Placebo gelNPC-12G gel placebo is administered topically twice a day for 12 weeks | Drug | Placebo gel |
Primary outcome
Improvements in angiofibroma
Time frame: 12 weeks
Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee
11 secondary outcomes
Improvements in angiofibroma
Time frame: Week 4 and 8 and follow-up Week 16
Improvements in angiofibroma
Time frame: Week 4, 8, 12 and follow-up Week 16
Improvements in redness of angiofibroma
Time frame: Week 4, 8, 12 and follow-up Week 16
Improvements in hypomelanotic macule and plaque of upper neck
Time frame: Week 4, 8, 12 and follow-up Week 16
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
Change in total score from baseline for DLQI and CDLQI
Time frame: Week 4, 8, 12 and follow-up Week 16
Adverse events
Time frame: 16 weeks
Serious adverse events
Time frame: 16 weeks
Laboratory findings
Time frame: 16 weeks
Vital sign
Time frame: 16 weeks
Sirolimus blood concentration
Time frame: Baseline, Week 4 and Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2017.
- Derived from this study: PubMed 29800026Wataya-Kaneda M, Ohno Y, Fujita Y, Yokozeki H, Niizeki H, Ogai M, Fukai K, Nagai H, Yoshida Y, Hamada I, Hio T, Shimizu K, Murota H. Sirolimus Gel Treatment vs Placebo for Facial Angiofibromas in Patients With Tuberous Sclerosis Complex: A Randomized Clinical Trial. JAMA Dermatol. 2018 Jul 1;154(7):781-788. doi: 10.1001/jamadermatol.2018.1408.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mari Wataya-Kaneda, MD, PhD principal investigator
Department of Dermatology, Graduate School of Medicine, Osaka University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NPC-12G gel in people with Tuberous Sclerosis and Angiofibroma, run by Nobelpharma at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvements in angiofibroma (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02635789, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2017.