GNE MyopathyPhase 3NCT04671472
Efficacy Confirmation Study of NPC-09
A Phase 3 study testing NPC-09 in people with GNE Myopathy and Distal Myopathy With Rimmed Vacuoles (DMRV), run by Nobelpharma at 5 sites in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 to 50 years
- Conditions the study is for
- GNE Myopathy, Distal Myopathy With Rimmed Vacuoles (DMRV), Hereditary Inclusion Body Myopathy (hIBM)
- What is being tested?
- NPC-09
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 5 sitesJapan
- Study dates
- 8 Feb 2021to 29 Mar 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Japan5 sites
National Center Hospital of Neurology and Psychiatry Hospita
Kodaira, Tokyo
Kumamoto University Hospital
Kumamoto
Nagoya University Hospital
Nagoya, Aichi-ken
Tohoku University Hospital
Sendai, Miyagi
Osaka University Hospital
Suita, Osaka
About this study
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.
Read the detailed description
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). It is an extremely rare progressive muscle disease, often occurring in the late teens to 30s, usually affecting the distal lower leg, especially the extensor muscles such as the tibialis anterior muscle, first, and weakness in both upper and lower limbs. However, the weakness of the quadriceps femoris is usually gradual. Although there are large individual differences, health management and deterioration of QOL will eventually become a problem, and in severe cases, constant assistance is required in daily life.
A double-blind comparative study conducted in Japan provided results suggesting efficacy, but the efficacy could not be confirmed in a large-scale international clinical trial, so this study is decided to be conducted. Oral administration of aceneuramic acid tablets 500 mg (SA-ER tablets) or placebo tablets of the same appearance, 4 tablets at a time, 3 times a day for 48 weeks will be examined for differences in efficacy. The target was a total of 10 cases, 7 cases in the active drug group, and 3 in the placebo group. The amount of change in upper extremity composite score (the sum of the average of the right and left HHD scores for grip, shoulder abductors, elbow flexors and elbow extensors) was used, and the secondary endpoints were the doctor's comprehensive evaluation and the GNE myopathy functional activity scale.
- Conditions
- GNE Myopathy, Distal Myopathy With Rimmed Vacuoles (DMRV), Hereditary Inclusion Body Myopathy (hIBM), Nonaka Disease
- Being tested
- NPC-09, NPC-09 placebo
- Keywords
- GNE myopathy, Distal myopathy with rimmed vacuoles (DMRV), Hereditary inclusion body myopathy (hIBM), Nonaka disease, sialic acid, aceneuramic acid, N-acetylneuraminic acid
- Medical subject headings
- Distal myopathy, Nonaka type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPC-09Drug
Also called Aceneuramic acid tablets
The drug will be administered by the oral route with the same manner
NPC-09 placeboDrug
Also called Aceneuramic acid matching placebo
The drug will be administered by the oral route with the same manner
| Study group | Role | What they receive |
|---|---|---|
| Aceneuramic acid tablets | Experimental | Aceneuramic acid tablets 6 g/day, divided 3 times a day for 48 weeks Receives: Drug: NPC-09 |
| Aceneuramic acid placebo tablets | Placebo comparator | Matching placebo 3 times a day for 48 weeks Receives: Drug: NPC-09 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 48
Secondary outcomes (6)
The effective rate in comprehensive judgement by the investigator
The investigator judges based on below 1 ~ 4 items.
- The manual muscle testing (0 - 5) or grip strength (kg)
- the upper extremity composite score (kg)
- the change in the upper extremity composite score (kg) compared with the transition of non-active drug administered GNE myopathy patients
- the other secondary endpoints
Measured: Week 48
Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) upper extremity domain score
Upper extremity functional activity is assessed using the upper extremity domain sore of the GNEM-FAS instrument. It consists of 8 items (score 0-4 for each item), total domain score is 0 to 32 with higher scores representing greater activity.
Measured: Week 48
Changes from Baseline in Individual muscle strength: Grip, shoulder abductors, elbow flexors, and elbow extensors comprising the upper extremity composite score (kg)
Muscle strength based on the maximum voluntary isometric contraction (MVIC) is measured.
Measured: Week 48
Change from baseline in knee extensors muscle strength (kg)
Muscle strength based on the maximum voluntary isometric contraction (MVIC) is measured.
Measured: Week 48
Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) mobility domain score
Mobility functional activity is assessed using the mobility domain sore of the GNEM-FAS instrument. It consists of 10 items (score 0-4 for each item), total domain score is 0 to 40 with higher scores representing greater activity.
Measured: Week 48
Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) self-care domain score
Self-care functional activity is assessed using the self-care domain sore of the GNEM-FAS instrument. It consists of 7 items (score 0-4 for each item), total domain score is 0 to 28 with higher scores representing greater activity.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start8 Feb 2021
- Primary completion29 Mar 2022
- Study completion29 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GNE MyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nobelpharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04671472
- Sponsor's protocol ID
- NPC-09-1
- Status last verified
- May 2022
- First submitted
- 30 Nov 2020
- Last updated
- 16 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37568154
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy Confirmation Study of NPC-09
- ClinicalTrials.gov ID
- NCT04671472
- Acronym / sponsor ID
- NPC-09-1
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- NobelpharmaIndustry (pharma, biotech, devices)
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- 29 Mar 2022 (actual)
- Study completion
- 29 Mar 2022 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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). It is an extremely rare progressive muscle disease, often occurring in the late teens to 30s, usually affecting the distal lower leg, especially the extensor muscles such as the tibialis anterior muscle, first, and weakness in both upper and lower limbs. However, the weakness of the quadriceps femoris is usually gradual. Although there are large individual differences, health management and deterioration of QOL will eventually become a problem, and in severe cases, constant assistance is required in daily life.
A double-blind comparative study conducted in Japan provided results suggesting efficacy, but the efficacy could not be confirmed in a large-scale international clinical trial, so this study is decided to be conducted. Oral administration of aceneuramic acid tablets 500 mg (SA-ER tablets) or placebo tablets of the same appearance, 4 tablets at a time, 3 times a day for 48 weeks will be examined for differences in efficacy. The target was a total of 10 cases, 7 cases in the active drug group, and 3 in the placebo group. The amount of change in upper extremity composite score (the sum of the average of the right and left HHD scores for grip, shoulder abductors, elbow flexors and elbow extensors) was used, and the secondary endpoints were the doctor's comprehensive evaluation and the GNE myopathy functional activity scale.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aceneuramic acid tablets | Experimental | Drug: NPC-09Aceneuramic acid tablets 6 g/day, divided 3 times a day for 48 weeks |
| Aceneuramic acid placebo tablets | Placebo comparator | Drug: NPC-09 placeboMatching placebo 3 times a day for 48 weeks |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NPC-09Also: Aceneuramic acid tabletsThe drug will be administered by the oral route with the same manner | Drug | Aceneuramic acid tablets |
| NPC-09 placeboAlso: Aceneuramic acid matching placeboThe drug will be administered by the oral route with the same manner | Drug | Aceneuramic acid placebo tablets |
Primary outcome
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)
Time frame: Week 48
Muscle strength based on the maximum voluntary isometric contraction (MVIC) is measured.
6 secondary outcomes
The effective rate in comprehensive judgement by the investigator
Time frame: Week 48
Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) upper extremity domain score
Time frame: Week 48
Changes from Baseline in Individual muscle strength: Grip, shoulder abductors, elbow flexors, and elbow extensors comprising the upper extremity composite score (kg)
Time frame: Week 48
Change from baseline in knee extensors muscle strength (kg)
Time frame: Week 48
Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) mobility domain score
Time frame: Week 48
Change from Baseline in GNE Myopathy Functional Activity Scale (GNEM-FAS) self-care domain score
Time frame: Week 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2022.
- Derived from this study: PubMed 37568154Mori-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.
- Individual participant dataSharing planned: No
Related trials for GNE Myopathy
RecruitingPhase 1/2
First-in-human Study of UX016 in GNEM
GNE Myopathy
Active, not recruitingPhase 2
Multi-Center Study of ManNAc for GNE Myopathy
GNE Myopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NPC-09 in people with GNE Myopathy and Distal Myopathy With Rimmed Vacuoles (DMRV), run by Nobelpharma at 5 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04671472, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2022.