Back to resultsSERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
Primary Purpose
Chronic Inflammatory Demyelinating Polyneuropathy, Peripheral Neuropathy, Charcot-Marie-Tooth Disease
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
MD1003
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Inflammatory Demyelinating Polyneuropathy focused on measuring Neuropathy, Demyelinating polyradiculoneuropathy
Eligibility Criteria
Inclusion Criteria:
- Male and female aged between 20 and 85 years.
- Patients fulfilling one of the following diagnosis:
- Five patients with chronic inflammatory demyelinating polyneuropathy on both clinical and neurophysiological grounds.
- Five patients with proven genetic diagnosis of CMT1a or CMT1b
- Five patients with anti-MAG polyneuropathy.
- Electrophysiological parameters worsening for the past 3 years
- Available EMG record, performed during the past 6 months to assess variability of NCV parameters
- Signed and dated written informed consent to participate in the study in accordance with local regulations
- Likely to be able to participate in all scheduled evaluation and complete all required study procedures,
- In the opinion of the investigator, the patient will be compliant and have a high probability of completing the study.
- Both male and female subjects who are not either surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year confirmed by a negative hormone panel) must commit to using TWO highly effective method of birth control for the duration of the study and for two months after the treatment termination.
Exclusion Criteria:
- Any general chronic handicapping disease other than peripheral neuropathy
- Impossibility to perform the 10 meters walking test
- Impossibility to assess electrophysiological parameters
- Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or cancer,
- Patients with hypersensitivity to MD1003 excipients (lactose)
- Laboratory tests out of normal range according to the reference laboratory values. Deviations may be accepted if considered by the investigator as not clinically significant with regards to the study continuation,
- Patients with history or presence of alcohol abuse or drug addiction,
- Patients likely to be non-compliant to the study procedures or for whom a long-term follow-up seems to be difficult to achieve.
- Any new medication for neuropathy initiated less than 3 months prior to inclusion. For CIDP patients, relapse in the past 3 months before inclusion.
- Not easily contactable by the investigator in case of emergency or not capable to call the investigator
- Subjects without effective contraception
Sites / Locations
- Hôpital Henri Mondor, Créteil, France
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MD1003
Arm Description
MD1003 100mg capsules, 1 capsule tid for 48 weeks
Outcomes
Primary Outcome Measures
Motor Nerve Conduction Velocity (m/Sec)
Absolute change from baseline at Week 48.
Distal Latency (Msec)
Absolute change from baseline at Week 48.
F Wave Latency (Msec)
Absolute change from baseline at Week 48.
Length of Motor Nerve Potential
Absolute change from baseline at W48.
Secondary Outcome Measures
ONLS (Overall Neuropathy Limitations Scale)
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.
Change From Baseline at Week 48 for Timed 10-meter Walk Test
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).
Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score
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 arm hanging down at the side.
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.
Grade 0: No movement is observed.
INCAT Sensory Sum Score (ISS)
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.
6-minute Walk Test
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.
Posturography Score
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.
Excitability Testing: Supernormality (%)
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 refractory period, the axon increases its excitability and the nerve fiber is more easily excited (the supernormal period). Depolarization of the node of Ranvier excites the adjacent internodes, which then charge with electric current as capacitors. Supernormality depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Strength-duration Time Constant (ms)
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.
Rheobase (mA)
This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.
Rheobase is the minimal strength of an electrical stimulus of infinitely long duration that is able to cause excitation. Low values are associated with better outcome (the nerve becomes more excitable).
Refractoriness (%)
This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline to 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'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Minimum Absolute Refractory Period (ms).
This secondary outcome measure is an electrophysiological testing endpoint. 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'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Maximum Absolute Refractory Period (ms).
This secondary outcome measure is an electrophysiological testing endpoint. 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'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Full Information
NCT ID
NCT02967679
First Posted
November 8, 2016
Last Updated
October 29, 2020
Sponsor
MedDay Pharmaceuticals SA
1. Study Identification
Unique Protocol Identification Number
NCT02967679
Brief Title
SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
Official Title
SERENDEM Study: MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 5, 2016 (Actual)
Primary Completion Date
March 18, 2019 (Actual)
Study Completion Date
March 18, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedDay Pharmaceuticals SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Inflammatory Demyelinating Polyneuropathy, Peripheral Neuropathy, Charcot-Marie-Tooth Disease, Charcot-Marie-Tooth Disease Type 1A, Charcot-Marie-Tooth Disease, Type 1B, Anti-MAG Neuropathy
Keywords
Neuropathy, Demyelinating polyradiculoneuropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MD1003
Arm Type
Experimental
Arm Description
MD1003 100mg capsules, 1 capsule tid for 48 weeks
Intervention Type
Drug
Intervention Name(s)
MD1003
Other Intervention Name(s)
High Dose Biotin
Primary Outcome Measure Information:
Title
Motor Nerve Conduction Velocity (m/Sec)
Description
Absolute change from baseline at Week 48.
Time Frame
48 weeks
Title
Distal Latency (Msec)
Description
Absolute change from baseline at Week 48.
Time Frame
48 weeks
Title
F Wave Latency (Msec)
Description
Absolute change from baseline at Week 48.
Time Frame
48 weeks
Title
Length of Motor Nerve Potential
Description
Absolute change from baseline at W48.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
ONLS (Overall Neuropathy Limitations Scale)
Description
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.
Time Frame
48 weeks
Title
Change From Baseline at Week 48 for Timed 10-meter Walk Test
Description
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).
Time Frame
48 weeks
Title
Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score
Description
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 arm hanging down at the side.
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.
Grade 0: No movement is observed.
Time Frame
48 weeks
Title
INCAT Sensory Sum Score (ISS)
Description
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.
Time Frame
48 weeks
Title
6-minute Walk Test
Description
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.
Time Frame
48 weeks
Title
Posturography Score
Description
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.
Time Frame
48 weeks
Title
Excitability Testing: Supernormality (%)
Description
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 refractory period, the axon increases its excitability and the nerve fiber is more easily excited (the supernormal period). Depolarization of the node of Ranvier excites the adjacent internodes, which then charge with electric current as capacitors. Supernormality depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Time Frame
48 weeks
Title
Strength-duration Time Constant (ms)
Description
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.
Time Frame
48 weeks
Title
Rheobase (mA)
Description
This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.
Rheobase is the minimal strength of an electrical stimulus of infinitely long duration that is able to cause excitation. Low values are associated with better outcome (the nerve becomes more excitable).
Time Frame
48 weeks
Title
Refractoriness (%)
Description
This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline to 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'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Time Frame
48 weeks
Title
Minimum Absolute Refractory Period (ms).
Description
This secondary outcome measure is an electrophysiological testing endpoint. 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'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Time Frame
48 weeks
Title
Maximum Absolute Refractory Period (ms).
Description
This secondary outcome measure is an electrophysiological testing endpoint. 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'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
Time Frame
Week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female aged between 20 and 85 years.
Patients fulfilling one of the following diagnosis:
Five patients with chronic inflammatory demyelinating polyneuropathy on both clinical and neurophysiological grounds.
Five patients with proven genetic diagnosis of CMT1a or CMT1b
Five patients with anti-MAG polyneuropathy.
Electrophysiological parameters worsening for the past 3 years
Available EMG record, performed during the past 6 months to assess variability of NCV parameters
Signed and dated written informed consent to participate in the study in accordance with local regulations
Likely to be able to participate in all scheduled evaluation and complete all required study procedures,
In the opinion of the investigator, the patient will be compliant and have a high probability of completing the study.
Both male and female subjects who are not either surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year confirmed by a negative hormone panel) must commit to using TWO highly effective method of birth control for the duration of the study and for two months after the treatment termination.
Exclusion Criteria:
Any general chronic handicapping disease other than peripheral neuropathy
Impossibility to perform the 10 meters walking test
Impossibility to assess electrophysiological parameters
Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or cancer,
Patients with hypersensitivity to MD1003 excipients (lactose)
Laboratory tests out of normal range according to the reference laboratory values. Deviations may be accepted if considered by the investigator as not clinically significant with regards to the study continuation,
Patients with history or presence of alcohol abuse or drug addiction,
Patients likely to be non-compliant to the study procedures or for whom a long-term follow-up seems to be difficult to achieve.
Any new medication for neuropathy initiated less than 3 months prior to inclusion. For CIDP patients, relapse in the past 3 months before inclusion.
Not easily contactable by the investigator in case of emergency or not capable to call the investigator
Subjects without effective contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alain CREANGE, MD
Organizational Affiliation
Hôpital Henri Mondor, Créteil, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frederic Sedel, MD
Organizational Affiliation
Medday Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital Henri Mondor, Créteil, France
City
Creteil
ZIP/Postal Code
94010
Country
France
12. IPD Sharing Statement
Links:
URL
http://www.medday-pharma.com
Description
Sponsor
Learn more about this trial
SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
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