NMF Kayabacho Bldg., 1-17-24, Shinkawa, Chuo-ku, Tokyo
+81-3-6670-3812
r-suzuki@nobelpharma.co.jp
Uchino Kuniyasu
Nobelpharma Co., Ltd.
NMF Kayabacho Bldg., 1-17-24, Shinkawa, Chuo-ku, Tokyo
+81-3-6670-3812
uchino.kuniyasu@nobelpharma.co.jp
Not Recruiting
Jan. 11, 2021
Feb. 08, 2021
10
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
- 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)
- Male or female, aged 18 - 50 years at Screening.
- Those who have a score of 24 points or more on the upper limbs of GNEM-FAS (GNE Myopathy Functional Activity Scale) and a disease period of 5 years or more and 15 years or less.
- Those whose upper limb muscle weakness has been confirmed from the results of manual muscle testing or grip strength measurements over the past few years, or if he/she has participated in the previous clinical ..trial, those who could confirm the upper extremity composite score decreased during the investigational drug is not administered.
- 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.
- 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.
- 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.
-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
- Has had any hypersensitivity to the investigational drug (SA-ER or its excipients) that, in the judgment of the investigator, places the subject at increased risk for adverse effects
-History of more than 30 days treatment with SA-ER and/or SA-IR in prior clinical trials in the past year
-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 adherence 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
-Those whom the investigator judges not to be appropriate for the subject
20age old over
50age old under
Both
Distal myopathy with rimmed vacuoles (DMRV), hereditary inclusion body myopathy (hIBM)
Oral administration of NPC-09 (Aceneuramic acid) for 48 weeks as compared with placebo
The primary endpoint is a comparison of changes in the upper extremity composite score (UEC score) from baseline to 48 weeks. Time-course analysis using a mixed-effects model is performed to estimate the change, the difference between the groups, and the 95% confidence interval at each time point in each administration group.
The presence or absence of outliers and the handling of missing values will be examined in a blinded review.
Comprehensive judgment by an investigator
Regarding (1) to (4) below, judge by any of improvement, immutability, deterioration, and undecidable (not applicable), and specify the reason for the judgment.
Then, the comprehensive efficacy in each patient is judged as effective, no effect, or undecidable by integrating them, and the reason for the judgment is specified.
(1) Whether to suppress the progression of the disease during the trial comparing before based on the manual muscle testing or grip strength?
(2) Whether to suppress the progression of the disease during the trial by comparing before based on the change in the upper extremity composite score?
(3) In the change in the upper extremity composite score, is the decrease smaller than the average value of the transition of non-active drug administered GNE myopathy patients** in domestic and overseas clinical trials who have the same background as this trial?
(4) Were there any improvements in the other secondary endpoints?
The validity of the judgment of the investigator will be examined at the case review meeting or a blinded review before opening the key and the problematic case should be reconfirmed with the investigator.
The effective rate and its confidence interval are shown for each administration group.
Other secondary endpoints
The other secondary endpoints are the changes from baseline to 48 weeks in the following items.
- GNE Myopathy Functional Activity Scale (GNEM-FAS) upper extremity domain score
- Individual muscle strength: Grip, shoulder abductors, elbow flexors, and elbow extensors comprising the upper extremity composite score: bilateral average muscle strength (kg)
- Knee extensor muscle strength: bilateral average muscle strength (kg)
- GNEM-FAS mobility domain score
- GNEM-FAS self-care domain score
- GNEM-FAS total score
Of these, for the scores of the upper extremity domain of the GNE Myopathy Functional Activity Scale (GNEM-FAS), the examination of outliers and the handling of missing values will be analyzed in the same manner as the above-mentioned primary endpoints.
Nobelpharma Co., Ltd.
Tohoku University Hospital Clinical Trial Review Committee
