Safety and Efficacy of NMD670 in Adult Patients with Type 1 and Type 2 Charcot-Marie-Tooth Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NMD Pharma A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

30 Aug 2024 → 5 Nov 2025

Decision date (initial)

2024-07-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

NMD Pharma A/S

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Others, Safety

To assess the clinical efficacy of NMD670 as rated by clinicians.

Conditions and MedDRA coding

Charcot-Marie-Tooth Disease Type 1 and Type 2

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female participants must be 18 to 70 years inclusive at the time of signing the ICF.
2. Diagnosis of CMT type 1 or 2 confirmed by genetic testing.
3. The following physical capabilities must be met without assistive devices such as AFOs (orthopaedic inserts are allowed) at screening (both must apply): a. 6MWT total distance within 1 standard deviation of the mean adjusted by age and sex from the provided CMT norm. b. Bilateral ankle dorsiflexion strength of 4 (inclusive) or less on the manual muscle testing scale.
4. Participants already receiving physical or occupational therapy or following a prescribed training regimen for more than 30 days prior to screening should continue their current treatment regimen throughout the study. Participants are not allowed to start physical or occupational therapy or a prescribed training regimen within 30 days of screening or during the study.
5. Participants taking medication for muscle cramps (e.g., magnesium) and/or pain (e.g., nonsteroidal anti-inflammatory drug [NSAID], neuropathic pain medication, or opiates) should be on a stable dose for at least 30 days prior to screening and should maintain a stable dose for the duration of the study.
6. Body mass index between 18 and 35 kg/m2 inclusive at screening and a minimum weight of 40 kg.
7. Female participants who are women of childbearing potential (WOCBP) and male participants with partners who are WOCBP must agree to use a highly effective contraception method during the study. Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (refer to Section 10.4, Appendix 4 for additional information).
8. Participant is capable of giving signed informed consent.
9. Participants willing and albe to comply with Syde(R)-related procedures (training on the device, daily use throughout from screening until the end of the study, and device return at the end of the study)

Exclusion criteria 23

1. Participants with other significant disease that may interfere with the interpretation of study data (e.g., other neuromuscular diseases) and/or ability to complete the tests, in the opinion of the Investigator.
2. Participants unable to undergo the ophthalmologic evaluation at screening.
3. Participants who require prohibited medication within 30 days of screening (or 5 half-lives of the medication, whichever is shorter) and/or are likely to require them during the study; prohibited medications include drugs showing relevant effects on NMJ transmission and drugs where the effect might be affected by potential metabolic drug-drug interactions with NMD670. Other current and recent (within 1 month prior to screening) treatments will be allowed if judged by the Investigator to be of no relevance for the study.
4. Use of daily assistive devices such as AFOs (orthopaedic inserts are allowed) for 4 weeks prior to screening and for the entire duration of the study. Daily AFO use is defined as individuals with CMT disesas who rely on assistive devices such as AFOs for regular functional support in daily activities. Patients who use an AFO but do not rely on it for regular activities and home activities or who use it only in specific situations, such as during outdoor activities, travelling, or work-related tasks, are not considered daily AFO users.
5. Participants who have received treatment with another IMP within 30 days (or 5 half-lives of the medication, whichever is longer) prior to day 1.
6. Participants with history of poor compliance with relevant therapy in the opinion of the Investigator.
7. Female participants who plan to become pregnant during the study or are currently pregnant or breastfeeding.
8. Severe deformity or ankle contracture that in the opinion of the Investigator would limit passive range of motion to interfere with performance of the tests.
9. Ankle surgery or other limb-surgery procedures related to CMT within 9 months of screening.
10. Moderate-to-severe neuropathic or inflammatory/musculoskeletal pain that in the opinion of the Investigator would interfere with performance of the tests.
11. Participants with a clinical diagnosis of gout or with serum uric acid greater than the upper limit of normal (ULN) at screening.
12. Participants with breast cancer, lymphoma, leukaemia, or any malignancy within the past 5 years. An exception of this 5-year requirement is basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease.
13. Study participants with a centrally read 12-lead ECG with findings considered to be clinically significant upon medical review. The clinical significance of the findings needs to be assessed by the Investigator to determine eligibility.
14. Participants with any of the following: a. Abnormal liver function test result defined as total bilirubin >1.5×ULN (participants with Gilbert’s syndrome can be included with total bilirubin >1.5×ULN if direct bilirubin is ≤1.5×ULN and ≤35% of total bilirubin). b. Abnormal liver transaminase levels at baseline and confirmed current or chronic history of liver disease including (but not limited to) hepatitis virus infections, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the Investigator. c. Known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). d. Abnormal renal function with estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiaology Collaboration (CKD-EPI) equation based on cystatin C24: <40 years: eGFR <75mL/min/1.73m2 40 to 65 years: eGFR <60mL/min/1.73m2 >65 years: eGFR <45mL/min/1.73m2, provided there is no proteinuria
15. Participants with laboratory test result abnormalities at screening considered clinically significant by the Investigator.
16. Participants with an ongoing significant psychiatric disorder (e.g., unstable and newly diagnosed major depressive disorder or unstable and newly diagnosed anxiety disorders).
17. Participants with alcohol abuse as judged by the Investigator or with positive drug screen results (cocaine, heroin, opiates, or marijuana) at screening. a. If positive for marijuana, criteria for drug abuse (as determined by the Investigator) is also needed to meet this exclusion criterion. b. If positive for opiates, the exclusion criterion is not met if opiates have been medically prescribed for the treatment of pain in CMT.
18. Participants with a positive HIV antibody test result.
19. Participants with positive serology test results for hepatitis B (unless due to vaccination, resolved natural infection, or passive immunisation, as confirmed with the Medical Monitor).
20. Participants positive for hepatitis C antibody.
21. Participants with a clinically significant history of allergic conditions (including drug allergies and anaphylactic reactions) or hypersensitivity to any component of the IMP.
22. Participant with myotonic disorders or those on drugs that induce or mask myotonia.
23. Paticipants with any of the following abnormalities at screening QT interval corrected for heart rate using Fridericias's correction (QTcF) a . greater than 450 msec for males and 460 msec for females b. PR interval greater than 220 msec c. Complete bundle branch block (QRS interval ≥120 msec) NOTE: This exclusion criterion is assessed by a central reader

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to day 21 in the total distance walked during the 6MWT for NMD670 vs placebo.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NMD Pharma A/S

Sponsor organisation

NMD Pharma A/S

Address

Palle Juul-Jensens Boulevard 82

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

NMD Pharma A/S

Contact name

Teresa Gidaro

Public contact point

Organisation

NMD Pharma A/S

Contact name

Caitlin Cornwall

Third parties 2

Locations

4 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 114 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications