UMIN-CTR Clinical Trial

Basic information
Public title	A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy and Safety of NPC-12G for Skin Lesions in Patients with Neurofibromatosis type 1
Acronym	NEDOC-2 Study
Scientific Title	A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy and Safety of NPC-12G for Skin Lesions in Patients with Neurofibromatosis type 1
Scientific Title:Acronym	NEDOC-2 Study
Region	Japan

Condition
Condition	Neurofibromatosis type 1
Classification by specialty	Dermatology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate efficacy and safety of NPC-12G at doses of 0.2% and 0.4% compared with placebo based on the changes in the volume of cutaneous tumor in patients with Neurofibromatosis type 1
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II,III

Assessment
Primary outcomes	Response rate on the changes from baseline in the volume of cutaneous tumor (measured with 3D camera) after 52 week treatment
Key secondary outcomes	1) Time course of changes from baseline in the volume of cutaneous tumor (measured with 3D camera) 2) Response rate on the changes from baseline in the volume of cutaneous tumor (measured with 3D camera) after 16 week, 28 week and 40 week treatment 3) Time course of changes from baseline in the area of cutaneous tumor (measured with ruler) 4) Improvement of cutaneous lesions after 28 and 52 week treatment judged by physician in charge

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	No need to know

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	0.2% NPC-12G gel topically administered twice a day for 52 weeks
Interventions/Control_2	0.4% NPC-12G gel topically administered twice a day for 52 weeks
Interventions/Control_3	Placebo gel topically administered twice a day for 52 weeks
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	3 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Patients diagnosed as neurofibromatosis type 1 according to the clinical diagnostic criteria in guideline of Japanese Dermatological Association 2) Patients with 10 skin lesions (at least 5 lesions) that can be selected from those of the maximum size. The skin lesions can be taken pictures by 3D camera and must satisfy all of the following conditions. a)Tumors of 3 mm or longer in longest diameter measured by ruler. b)Tumors located solitary c)Skin lesions without hair d)Tumors of mountain-like shape with no shadows when taken pictures from above (bulb shape or gourd shape tumor should not be selected) e)Tumors not located on the skin with large expansion and contraction such as inside of the elbow or the scruff. 3) Patients who is 3 years old or elder 4) Patients who provide written informed consent by themselves or legally acceptable representatives
Key exclusion criteria	1) Patients who treated with mTOR inhibitors (sirolimus, everolimus or temsirolimus), within 12 months prior to enrollment. 2) Patients who treated with RAS-MAPK inhibitors (sorafenib, regorafenib or lenvatinib), within 12 months prior to enrollment. 3) Patients who have active infectious lesions. 4) Patients who have abnormal findings (pneumonic lesions) by chest X-ray inspection. 5) Patients with creatinine clearance less than 50ml/min. 6) Patients with uncontrolled dyslipidemia (serum triglyceride is 500mg / dL or more, or LDL cholesterol is 190mg / dL or more even treated) 7) Patients who have severe complications such as cardiac disease, liver disease, pulmonary disease, hematological disorder or malignant tumor . 8) Patients who have previously experienced alcoholic sensitivity or allergy to sirolimus. 9) Patients who are pregnant or lactating. 10) Patients who cannot agree to use effective contraceptive methods during the study period and until 8 weeks after treatment. 11) Patients who have entered another clinical trial within 6 months prior to enrollment.
Target sample size	63

Research contact person
Name of lead principal investigator	1st name Mari Middle name Last name Kaneda
Organization	Osaka University Hospital
Division name	Department of Dermatology
Zip code	565-0871
Address	2-15 Yamadaoka, Suita, Osaka, Japan
TEL	06-6879-3031
Email	mkaneda@derma.med.osaka-u.ac.jp

Public contact
Name of contact person	1st name Mari Middle name Last name Kaneda
Organization	Osaka University Hospital
Division name	Department of Dermatology
Zip code	565-0871
Address	2-15 Yamadaoka, Suita, Osaka, Japan
TEL	06-6879-3031
Homepage URL
Email	mkaneda@derma.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Institutional Review Board of Osaka University hospital
Address	2-2 Yamadaoka, Suita, Osaka, Japan
Tel	06-6210-8290
Email	shiken@hp-crc.med.osaka-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	大阪大学医学部附属病院（大阪府）、東京慈恵会医科大学附属病院（東京都）、 鳥取大学医学部附属病院（鳥取県）、福岡大学病院（福岡県）

Other administrative information
Date of disclosure of the study information	2019 Year 04 Month 22 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	76
Results	0.2% NPC-12G, 0.4% NPC12-G and placebo were topically administered to the skin lesion of the patients with neurofibromatosis type 1 for 52 weeks. There were no statistical differences between the NPC12-G group and the placebo group regarding the efficacy evaluation. There were no serious side effects observed and there were no special concerns regarding the safety of 0.2% NPC-12G and 0.4% NPC12-G when topically administered to the skin lesion of the patients with neurofibromatosis type 1 for 52 weeks.
Results date posted	2021 Year 07 Month 05 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Male: 22 cases, Female: 54 cases Mean age: 48.3, Minimum age: 19, Maximum age: 78
Participant flow	Informed consent obtained: 84 cases Enrolled: 76 cases 0.2% group: 25 cases, 0.4% group: 24 cases, Placebo group: 27 cases
Adverse events	Adverse events observed were at 92.0% (23/25) of the cases in the 0.2% group, 87.5% (21/24) in the 0.4% group and 70.4% (19/27) in the placebo group. Side effects observed were at 52.0% (13/25) of the cases in the 0.2% group, 45.8% (11/24) in the 0.4% group and 37.0% (10/27) in the placebo group. No serious side effects were observed.
Outcome measures	Primary outcome measures showed there were no responders in any of the groups with the evaluation of the response rate after 52 weeks administration and there were no statistical differences observed between the NPC12-G group and the placebo group.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2019 Year 03 Month 22 Day
Date of IRB	2019 Year 03 Month 22 Day
Anticipated trial start date	2019 Year 05 Month 10 Day
Last follow-up date	2021 Year 02 Month 28 Day
Date of closure to data entry	2021 Year 03 Month 31 Day
Date trial data considered complete	2021 Year 03 Month 31 Day
Date analysis concluded

Other
Other related information

Management information
Registered date	2019 Year 04 Month 16 Day
Last modified on	2021 Year 10 Month 19 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041614