Efficacy Confirmation Study of NPC-09

NCT04671472 | Completed Phase 3

• 1 other identifier: NPC-09-1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

GNE myopathy is a distal myopathy that is thought to be caused by a mutation in the GNE gene that encodes an enzyme in the biosynthetic process of aceneuramic acid (typical sialic acid). The investigators will examine the efficacy and safety of aceneuramic acid (SA-ER tablets) 6g daily for 48 weeks in patients with GNE myopathy in a placebo-controlled, double-blind, controlled trial.

Conditions

GNE Myopathy; Distal Myopathy With Rimmed Vacuoles (DMRV); Hereditary Inclusion Body Myopathy (hIBM); Nonaka Disease

Keywords

GNE myopathy; Distal myopathy with rimmed vacuoles (DMRV); Hereditary inclusion body myopathy (hIBM); Nonaka disease; sialic acid; aceneuramic acid; N-acetylneuraminic acid

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in the upper extremity composite score (the sum of the average of the right and left muscle strength measured by HHD (Hand held dynamometer) (kg) for grip, shoulder abductors, elbow flexors and elbow extensors)

  Muscle strength based on the maximum voluntary isometric contraction (MVIC) is measured.

  Week 48

Secondary Outcomes (6)

• The effective rate in comprehensive judgement by the investigator

  Week 48

• Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) upper extremity domain score

  Week 48

• Changes from Baseline in Individual muscle strength: Grip, shoulder abductors, elbow flexors, and elbow extensors comprising the upper extremity composite score (kg)

  Week 48

• Change from baseline in knee extensors muscle strength (kg)

  Week 48

• Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) mobility domain score

  Week 48

Study Arms (2)

Aceneuramic acid tablets

EXPERIMENTAL

Aceneuramic acid tablets 6 g/day, divided 3 times a day for 48 weeks

Drug: NPC-09

Aceneuramic acid placebo tablets

PLACEBO COMPARATOR

Matching placebo 3 times a day for 48 weeks

Drug: NPC-09 placebo

Interventions

NPC-09 DRUG

The drug will be administered by the oral route with the same manner

Also known as: Aceneuramic acid tablets

Aceneuramic acid tablets

NPC-09 placebo DRUG

The drug will be administered by the oral route with the same manner

Also known as: Aceneuramic acid matching placebo

Aceneuramic acid placebo tablets

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nobelpharma: lead

Study Sites (5)

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, Japan

Location

Osaka University Hospital

Suita, Osaka, Japan

Location

National Center Hospital of Neurology and Psychiatry Hospita

Kodaira, Tokyo, Japan

Location

Kumamoto University Hospital

Kumamoto, Japan

Location

Related Publications (1)

• Mori-Yoshimura M, Suzuki N, Katsuno M, Takahashi MP, Yamashita S, Oya Y, Hashizume A, Yamada S, Nakamori M, Izumi R, Kato M, Warita H, Tateyama M, Kuroda H, Asada R, Yamaguchi T, Nishino I, Aoki M. Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan. Orphanet J Rare Dis. 2023 Aug 11;18(1):241. doi: 10.1186/s13023-023-02850-y.

  PMID: 37568154 DERIVED

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 17, 2020
• Study Start: February 8, 2021
• Primary Completion: March 29, 2022
• Study Completion: March 29, 2022
• Last Updated: May 16, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5)