UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase II/III Study of NPC-09 (N-acetylneuraminic acid) in Patients with GNE Myopathy (GNEM)
Title of the study (Brief title)	A Phase II/III Study of NPC-09 (N-acetylneuraminic acid) in Patients with GNE Myopathy (GNEM)
Region	Japan

Condition
Condition	GNE myopathy (Distal myopathy with rimmed vacuoles (DMRV), hereditary inclusion body myopathy (hIBM) or Nonaka disease)
Classification by specialty	Neurology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Evaluate the efficacy and safety of 6g/day for 48weeks SA-ER treatment in GNE myopathy patients with a randomised, double-blind, placebo-controlled study
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase II,III

Assessment
Primary outcomes	The amount of change in upper extremity muscle strength composite score (UEC score) between at the time before the start of administration and at the point of last evaluation
Key secondary outcomes	Analyses of secondary efficacy variables will follow the same methods as the primary analyses of the primary endpoint, where data are available. - GNEM-FAS mobility domain score - GNEM-FAS upper extremity domain score - Lower extremity muscle strength composite score (LEC score) - Sit-to-stand score calculated as the number of times a subject can rise from a sitting to a standing position in a 30-second period - Weighted arm lift score calculated as the number of times a subject can raise a 1kg weight overhead in a 30-second period - Muscle strength in the knee extensors: bilateral total force (in kg) and percent predicted using published normative data adjusted for age, gender, and weight - Walking ability as measured by distance walked in the six-minute walk test (6MWT), which will be reported as distance in meters and percent predicted based on normative data for age and gender <Tertiary outcomes> Analyses of tertiary variables will follow the same methods as the primary analyses of the primary endpoint, where data are available. - UEC score based on percent predicted bilateral strength recorded in the upper extremity muscle groups - LEC score based on percent predicted bilateral strength recorded in the upper extremity muscle groups - Muscle strength (total force in kg) for each individual muscle group comprising the UEC and LEC Percent predicted muscle strength for each individual muscle group comprising the UEC and LEC using published normative data adjusted for age, gender, and weight - GNEM-FAS total score - GNEM-FAS self-care domain score - Health-related quality of life as measured by the Individual Neuromuscular Quality of Life Questionnaire (INQoL) - Clinical Global Impression (CGI) scores - Creatine kinase (CK) levels in serum - Trough (pre-dose) SA levels in serum (free) and urine (free, total, and bound; corrected for creatinine)

Base
Study type	Interventional

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

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	SA-ER 2g 3 times oral dosing a day for 48 consecutive weeks
Interventions/Control_2	placebo 3 times oral dosing a day for 48 consecutive weeks
Interventions/Control_3
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	20 years-old <=
Age-upper limit	50 years-old >=
Gender	Male and Female
Key inclusion criteria	-Willing and able to provide written, signed informed consent after the nature of the study has been explained, and before any research-related procedures are conducted -Have a documented diagnosis of GNEM, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/MNK enzyme (genotyping will not be conducted in this study) -Able to provide reproducible force in elbow flexors (i.e. two dynamometry force values with no more than 15% variability in the dominant arm) at Screening -Patients who are able to walk a minimum of 200 meters during the 6MWT at Screening, are able to walk without the use of assistive devices, including a cane, crutch(es), walker, wheelchair or scooter (ankle foot orthoses [AFOs] are permitted) -Willing and able to comply with all study procedures -Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a bilateral sapling-oophorectomy and are sexually active must consent to use an effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation or true abstinence) from the period following the signing of the informed consent through 3 months after last dose of study drug -Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause for at least two years, have had tubal ligation at least one year prior to Screening, or who have had a total hysterectomy or bilateral salpingo-oophorectomy
Key exclusion criteria	-Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites; intravenous immunoglobulin (IVIG); or anything that can be metabolized to produce SA in the body within 60 days prior to the Screening Visit -History of more than 30 days treatment with SA-ER and/or SA-IR in prior clinical trials in the past year -Has had any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects -Has serum transaminase (i.e. aspartate aminotransferase [AST] or gamma-glutamyl transpeptidase [GGT]) levels greater than 3X the upper limit of normal (ULN) for age/gender, or serum creatinine of greater than 2X ULN at Screening -Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study -Use of any investigational product or investigational medical device within 30 days prior to Screening, or anticipated requirement for any investigational agent prior to completion of all scheduled study assessments -Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment or may not allow safe participation in the study -Has a concurrent disease, active suicidal ideation, or other condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety -More than 400 mL blood donation within 16 weeks -Presence of alcohol or drug dependency -Patients whom the investigator judges not to be appropriate for the subject
Target sample size	20

Research contact person
Name of lead principal investigator	Masashi Aoki, MD, PhD
Organization	Tohoku University School of Medicine
Division name	Neurology
Address	1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574 Japan
TEL	022-717-7189
Email	aokim@med.tohoku.ac.jp

Public contact
Name of contact person	Akifumi Suzuki
Organization	Clinical Research, Innovation, and Education Center, Tohoku University Hospital (CRIETO)
Division name	Department of Development Promotion
Address	1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
TEL	022-717-7136
Homepage URL
Email	aksuzuki@hosp.tohoku.ac.jp

Sponsor
Institute	Tohoku University Hospital, Department of Neurology
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Government offices of other countries
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Nobelpharma Co., Ltd.
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW	2016.1.6.,3回

Institutions
Institutions	東北大学病院（宮城県）、国立精神・神経医療研究センター病院（東京都）、名古屋大学医学部附属病院（愛知県）、大阪大学医学部附属病院（大阪府）、熊本大学医学部附属病院（熊本県）

Other administrative information
Date of disclosure of the study information	2016 Year 01 Month 25 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 11 Month 27 Day
Anticipated trial start date	2016 Year 02 Month 01 Day
Last follow-up date	2017 Year 09 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 01 Month 21 Day
Last modified on	2017 Year 12 Month 18 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023425