UMIN-CTR Clinical Trial

Public title

A Phase II/III Study of NPC-09 (N-acetylneuraminic acid) in Patients with GNE Myopathy (GNEM)

Acronym

A Phase II/III Study of NPC-09 (N-acetylneuraminic acid) in Patients with GNE Myopathy (GNEM)

Scientific Title

A Phase II/III Study of NPC-09 (N-acetylneuraminic acid) in Patients with GNE Myopathy (GNEM)

Scientific Title:Acronym

A Phase II/III Study of NPC-09 (N-acetylneuraminic acid) in Patients with GNE Myopathy (GNEM)

Region

Japan

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

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

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)

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Masashi Aoki, MD, PhD

Organization

Tohoku University School of Medicine

Division name

Neurology

Zip code

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574 Japan

TEL

022-717-7189

Email

aokim@med.tohoku.ac.jp

Name of contact person

1st name
Middle name
Last name	Akifumi Suzuki

Organization

Clinical Research, Innovation, and Education Center, Tohoku University Hospital (CRIETO)

Division name

Department of Development Promotion

Zip code

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

TEL

022-717-7136

Homepage URL

Email

aksuzuki@hosp.tohoku.ac.jp

Institute

Tohoku University Hospital, Department of Neurology

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Japan

Co-sponsor

Nobelpharma Co., Ltd.

Name of secondary funder(s)

Organization

Address

Tel

Email

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

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）

Date of disclosure of the study information

2016

Year

01

Month

25

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

11

Month

27

Day

Date of IRB

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

Other related information

Registered date

2016

Year

01

Month

21

Day

Last modified on

2017

Year

12

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023425