Tuberous SclerosisPhase 3NCT02634931
Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex
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 safety and efficacy of long-term treatment with NPC-12G gel (0.2% sirolimus gel) to angiofibroma and other skin lesions in patients with tuberous sclerosis complex in the open-label trial. 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?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteJapan
- Study dates
- Dec 2015to Oct 2018
- 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 skin lesions such as angiofibroma, white macules or plaque upper neck associated with tuberous sclerosis complex at the screening visit or the baseline visit
- Patients or his/her guardian who agree to use the test drug (NPC-12G gel) or who want to participate in the trial again following participation in Phase III trial (NPC-12G-1)
- Patient who are considered to be an appropriate patient to participate in the trial by investigator
- 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 have offered to withdraw from Phase III trial (NPC-12G-1) and have been discontinued
- Patients who have not applied the test drug topically more than 25% of whole applications without appropriate reason for Phase III trial (NPC-12G-1)
- 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 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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- Female patients who may be pregnancy or are lactating
- Patients who cannot agree to take appropriate measures of contraception until completion of the trial or follow-up period after discontinuation from informed consent
- Patients who have participated in other clinical trial other than Phase III trial (NPC-12G-1) and have taken a trial drug within 6 months before informed consent
- 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 Long-term, Single-arm, Open-label Trial of NPC-12G (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 safety and efficacy of long-term treatment with NPC-12G gel (0.2% sirolimus gel) to angiofibroma and other skin lesions in patients with tuberous sclerosis complex in the open-label trial.
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 a TSC-specific facial skin lesion, 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 and surgical treatments, but there are problems as many relapses, deficiency of evidence, change of pigment, scar and risk of infection.
This is a multicenter and open-label trial. The trial consists of two phase. In the first trial phase for 52 weeks, the efficacy as well as the safety is evaluated. For the second trial phase the trial will be continued until the date of approval of NDA for NPC-12G. The safety is evaluated during the second trial phase, but not the efficacy. Patients who meet all entry criteria for the trial apply 0.2% NPC-12G gel twice a day. Patients will visit at 4 to 5-week intervals for the first 6 months of the first trial phase, and then 3 months intervals thereafter.
- Conditions
- Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule, Plaque
- Being tested
- NPC-12G 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 52 weeks or longer
| Study group | Role | What they receive |
|---|---|---|
| NPC-12G gel | Experimental | NPC-12G gel is containing 0.2% Sirolimus Receives: Drug: NPC-12G gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
The discontinuation rate due to adverse events
The first discontinuation in each patient due to adverse events is assessed.Completion of week 26 and 52 are cut-off points for interim-analyses by Kaplan-Meier method
Measured: 52 weeks and longer
Secondary outcomes (14)
Adverse events and adverse events related to the test drug
The number of discontinuation/ resume due to adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Measured: 52 weeks and longer
Adverse events related to the test drug leading to the discontinuation permanently
The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Measured: 52 weeks and longer
Serious adverse events and serious adverse events related to the test drug
The incidence of serious adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Measured: 52 weeks and longer
Adverse events and adverse events related to the test drug leading to modification of dosage and administration
The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Measured: 52 weeks and longer
Significant adverse events and significant adverse events related to the test drug
The incidence of significant adverse events such as local irritation are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Measured: 52 weeks and longer
Laboratory tests, vital signs
Completion of week 26 and 52 are cut-off points for interim-analyses
Measured: Baseline and every 3 months for laboratory tests, every scheduled visit for vital sign]
Blood level of sirolimus
Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit
Measured: Baseline and every 3 months only for the first trial phase
Improvements in angiofibroma
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 4, 8, 12, 26, 39 and 52
Improvements in sizes of angiofibroma
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 4, 8, 12, 26, 39 and 52
Improvements in redness of angiofibroma
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 4, 8, 12, 26, 39 and 52
Improvements in white macule and plaque upper neck
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 4, 8, 12, 26, 39 and 52
The rate of patients evaluated ''improvement'' or more (improvement rate) in above the efficacy measures.
Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 4, 8, 12, 26, 39 and 52
Change in total score of DLQI and CDLQI from baseline
DLQI for subjects 16 years old and greater, or CDLQI for children of less than 16 years old is assessed by patients. Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 4, 8, 12, 26, 39 and 52
Degree of patient's satisfaction
Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.
Measured: Week 12, 26, 39 and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionOct 2018
- Study completionOct 2018
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 94 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
- NCT02634931
- Sponsor's protocol ID
- NPC-12G-2
- Status last verified
- Dec 2015
- First submitted
- 16 Dec 2015
- Last updated
- 20 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Wataya-Kaneda M, Nagai H, Ohno Y, Yokozeki H, Fujita Y, Niizeki H, Yoshida K, Ogai M, Yoshida Y, Asahina A, Fukai K, Tateishi C, Hamada I, Takahata T, Shimizu K, Shimasaki S, Murota H. Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial. Dermatol Ther (Heidelb). 2020 Aug;10(4):635-650. doi: 10.1007/s13555-020-00387-7. Epub 2020 May 8.
PubMed 32385845
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Long-term, Single-arm, Open-label Trial of NPC-12G (Topical Formulation of Sirolimus) to Angiofibroma and Other Skin Lesions in Patients With Tuberous Sclerosis Complex
- ClinicalTrials.gov ID
- NCT02634931
- Acronym / sponsor ID
- NPC-12G-2
- 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
- 94 participants (actual)
- Lead sponsor
- NobelpharmaIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 18 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 safety and efficacy of long-term treatment with NPC-12G gel (0.2% sirolimus gel) to angiofibroma and other skin lesions in patients with tuberous sclerosis complex in the open-label trial.
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 a TSC-specific facial skin lesion, 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 and surgical treatments, but there are problems as many relapses, deficiency of evidence, change of pigment, scar and risk of infection.
This is a multicenter and open-label trial. The trial consists of two phase. In the first trial phase for 52 weeks, the efficacy as well as the safety is evaluated. For the second trial phase the trial will be continued until the date of approval of NDA for NPC-12G. The safety is evaluated during the second trial phase, but not the efficacy. Patients who meet all entry criteria for the trial apply 0.2% NPC-12G gel twice a day. Patients will visit at 4 to 5-week intervals for the first 6 months of the first trial phase, and then 3 months intervals thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NPC-12G gel | Experimental | Drug: NPC-12G gelNPC-12G gel is containing 0.2% Sirolimus |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 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 skin lesions such as angiofibroma, white macules or plaque upper neck associated with tuberous sclerosis complex at the screening visit or the baseline visit
- Patients or his/her guardian who agree to use the test drug (NPC-12G gel) or who want to participate in the trial again following participation in Phase III trial (NPC-12G-1)
- Patient who are considered to be an appropriate patient to participate in the trial by investigator
Key exclusion criteria (10 listed)
- Patients who have offered to withdraw from Phase III trial (NPC-12G-1) and have been discontinued
- Patients who have not applied the test drug topically more than 25% of whole applications without appropriate reason for Phase III trial (NPC-12G-1)
- 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 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 52 weeks or longer | Drug | NPC-12G gel |
Primary outcome
The discontinuation rate due to adverse events
Time frame: 52 weeks and longer
The first discontinuation in each patient due to adverse events is assessed.Completion of week 26 and 52 are cut-off points for interim-analyses by Kaplan-Meier method
14 secondary outcomes
Adverse events and adverse events related to the test drug
Time frame: 52 weeks and longer
Adverse events related to the test drug leading to the discontinuation permanently
Time frame: 52 weeks and longer
Serious adverse events and serious adverse events related to the test drug
Time frame: 52 weeks and longer
Adverse events and adverse events related to the test drug leading to modification of dosage and administration
Time frame: 52 weeks and longer
Significant adverse events and significant adverse events related to the test drug
Time frame: 52 weeks and longer
Laboratory tests, vital signs
Time frame: Baseline and every 3 months for laboratory tests, every scheduled visit for vital sign]
Blood level of sirolimus
Time frame: Baseline and every 3 months only for the first trial phase
Improvements in angiofibroma
Time frame: Week 4, 8, 12, 26, 39 and 52
Improvements in sizes of angiofibroma
Time frame: Week 4, 8, 12, 26, 39 and 52
Improvements in redness of angiofibroma
Time frame: Week 4, 8, 12, 26, 39 and 52
Improvements in white macule and plaque upper neck
Time frame: Week 4, 8, 12, 26, 39 and 52
The rate of patients evaluated ''improvement'' or more (improvement rate) in above the efficacy measures.
Time frame: Week 4, 8, 12, 26, 39 and 52
Change in total score of DLQI and CDLQI from baseline
Time frame: Week 4, 8, 12, 26, 39 and 52
Degree of patient's satisfaction
Time frame: Week 12, 26, 39 and 52
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 20 Feb 2019.
- Derived from this study: PubMed 32385845Wataya-Kaneda M, Nagai H, Ohno Y, Yokozeki H, Fujita Y, Niizeki H, Yoshida K, Ogai M, Yoshida Y, Asahina A, Fukai K, Tateishi C, Hamada I, Takahata T, Shimizu K, Shimasaki S, Murota H. Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial. Dermatol Ther (Heidelb). 2020 Aug;10(4):635-650. doi: 10.1007/s13555-020-00387-7. Epub 2020 May 8.
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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 6 inclusion and 10 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 20 Feb 2019. 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. 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?
The discontinuation rate due to adverse events (time frame: 52 weeks and longer). 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 NCT02634931, 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 20 Feb 2019.