NCT02967679

SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study

Completed Phase 2 Results posted Last updated 2 November 2020

What this trial tests

Phase 2 trial testing MD1003 in Chronic Inflammatory Demyelinating Polyneuropathy in 15 participants. Completed in 18 March 2019.

Timeline

5 December 2016

Primary endpoint
18 March 2019

18 March 2019

Quick facts

Lead sponsor	MedDay Pharmaceuticals SA
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	15
Start date	5 December 2016
Primary completion	18 March 2019
Estimated completion	18 March 2019
Sites	1 location across France

Drugs / interventions tested

• MD1003 — full drug profile →

Conditions studied

• Chronic Inflammatory Demyelinating Polyneuropathy — all drugs for Chronic Inflammatory Demyelinating Polyneuropathy →
• Peripheral Neuropathy — all drugs for Peripheral Neuropathy →
• Charcot-Marie-Tooth Disease — all drugs for Charcot-Marie-Tooth Disease →
• Charcot-Marie-Tooth Disease Type 1A — all drugs for Charcot-Marie-Tooth Disease Type 1A →

Sponsor

MedDay Pharmaceuticals SA — full company profile →

Who can join

Adults 20 to 85, any sex, with Chronic Inflammatory Demyelinating Polyneuropathy or Peripheral Neuropathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Motor Nerve Conduction Velocity (m/Sec) Primary · 48 weeks

Absolute change from baseline at Week 48.

Group	Value	95% CI
MD1003	1.67	± 11.45

Distal Latency (Msec) Primary · 48 weeks

Absolute change from baseline at Week 48.

Group	Value	95% CI
MD1003	0.20	± 8.89

F Wave Latency (Msec) Primary · 48 weeks

Absolute change from baseline at Week 48.

Group	Value	95% CI
MD1003	4.8	± 8.40

Length of Motor Nerve Potential Primary · 48 weeks

Absolute change from baseline at W48.

Group	Value	95% CI
MD1003	8.5	± 16.50

ONLS (Overall Neuropathy Limitations Scale) Secondary · 48 weeks

The ONLS focuses on upper and lower limb functions, and consists of a checklist for interviewing patients. It is scored from 0 to 5 on the upper limb section and from 0 to 7 on the lower limb section. A score of 0 indicates no limitations (the ceiling of the scale) and a score of 5 or 7 indicates no purposeful movement. Absolute change from baseline at week 48.

Group	Value	95% CI
MD1003	-0.5	± 1.4

Change From Baseline at Week 48 for Timed 10-meter Walk Test Secondary · 48 weeks

Absolute change from baseline at week 48. The patient is instructed to walk at normal pace for 10 meters. Start and stop of performance time coincides with the toes of the leading foot crossing the 2-m mark and the 8-m mark, respectively. From these data, the speed may be calculated by dividing the middle 6 m by the time (in seconds).

Group	Value	95% CI
MD1003	-0.6	± 1.2

Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score Secondary · 48 weeks

MRC score assessed in 19 muscles. The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle. The patient's effort is graded on a scale of 0-5: Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance. Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. As an example, the elbow can be moved from full extension to full flexion starting with the

Group	Value	95% CI
MD1003	4.5	± 8.2

INCAT Sensory Sum Score (ISS) Secondary · 48 weeks

This sensory scale comprises pin prick and vibration sense plus a two point discrimination value in the arms and legs, and ranges from 0 ("normal sensation") to 20 ("most severe sensory deficit"). Absolute change from baseline at week 48.

Group	Value	95% CI
MD1003	-2.2	± 2.9

6-minute Walk Test Secondary · 48 weeks

The 6MWT is a practical simple test that requires a 30 m (100-ft) hallway. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. Absolute change from baseline at week 48.

Group	Value	95% CI
MD1003	61.1	± 48.9

Posturography Score Secondary · 48 weeks

Computerized dynamic posturography (CDP) is a non-invasive specialized clinical assessment technique used to quantify the central nervous system adaptive mechanisms (sensory, motor and central) involved in the control of posture and balance, both in normal and abnormal conditions. Absolute change of speed in spontaneous speed condition from baseline at week 48.

Group	Value	95% CI
MD1003	0.111	± 0.201

Excitability Testing: Supernormality (%) Secondary · 48 weeks

Nerve excitability testing is a non-invasive approach in investigating the pathophysiology of peripheral nerve disorders, which determines the electrical properties of the nerve membrane at the site of stimulation. Absolute change from baseline at week 48. After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). During the 10-30 ms following the end of the

Group	Value	95% CI
MD1003	9.84	± 28.16

Strength-duration Time Constant (ms) Secondary · 48 weeks

This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48. Strength-duration Time Constant (ms) is a measurement of excitability, defined as the duration of the stimulus that has twice the strength of the rheobase current (see below). The lower the rheobase is, the higher is the Strenght duration time constant. Accordingly, higer values of SDTC are associated with better outcome.

Group	Value	95% CI
MD1003	0.068	± 0.112

Adverse events — posted to ClinicalTrials.gov

Time frame: 52 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MD1003

Serious: 2/15 (13%)

Deaths: 0/15

Serious adverse events (2 terms)

Reaction	System	MD1003
Clear cell renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Autoimmune encephalopathy	Nervous system disorders	—

Other adverse events (30 terms — click to expand)

Reaction	System	MD1003
Insomnia	Nervous system disorders	—
arthralgia	Musculoskeletal and connective tissue disorders	—
Fatigue	General disorders	—
Laboratory test interference	Investigations	—
Pruritus	Skin and subcutaneous tissue disorders	—
Gastric disorder	Gastrointestinal disorders	—
balance disorder	Nervous system disorders	—
Memory impairment	Nervous system disorders	—
Muscle contractions involuntary	Nervous system disorders	—
Neuralgia	Nervous system disorders	—
Restless legs syndrome	Nervous system disorders	—
Sciatica	Nervous system disorders	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Oedema peripheral	General disorders	—
Diarrhoea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Ankle fracture	Injury, poisoning and procedural complications	—
Burn oesophageal	Injury, poisoning and procedural complications	—
Foot fracture	Injury, poisoning and procedural complications	—
Haemoglobin decreased	Investigations	—
Alopecia	Skin and subcutaneous tissue disorders	—
Rash papular	Skin and subcutaneous tissue disorders	—
Urinary tract infection	Infections and infestations	—
Depression	Psychiatric disorders	—
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	—
Breast reconstruction	Surgical and medical procedures	—
Hypertension	Vascular disorders	—

Most-reported serious reactions: Clear cell renal cell carcinoma, Autoimmune encephalopathy.

Data from ClinicalTrials.gov NCT02967679 adverse events section.

Sponsor's own description

The single-center, open-label Phase II study has the objective of assess the effect of MD1003 on motor and sensory conduction in patients suffering from demyelinating polyneuropathies in 15 subjects.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Treating pediatric neuromuscular disorders: The future is now.
   Dowling JJ, D Gonorazky H, Cohn RD, Campbell C. · · 2018 · cited 83× · PMID 28889642 · DOI 10.1002/ajmg.a.38418
2. Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches.
   McCulloch MK, Mehryab F, Rashnonejad A. · · 2024 · cited 4× · PMID 39273178 · DOI 10.3390/ijms25179227
3. High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study.
   Créange A, Hutin E, Sedel F, Le Vigouroux L, et al · · 2023 · cited 4× · PMID 37899433 · DOI 10.1186/s12883-023-03440-y