Effect of MD1003 in Amyotrophic Lateral Sclerosis

NCT03114215 | Completed Phase 2 DMC

• 1 other identifier: MD1003CT2015-02-ALS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 6-month double blind randomized 2:1 placebo-controlled study with two arms (placebo, biotin 300 mg/day). The study will be followed by a 6-month extension phase during which all patients will receive biotin 300 mg/day.

Conditions

ALS; Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Keywords

Biotin; MD1003; ALSFRS-R

Outcome Measures

Primary Outcomes (2)

• Recording of adverse events

  All adverse events in two groups will be recorded.

  6 months

• Laboratory testing (haematology and biochemistry panel)

  * RBC (red blood cell), WBC (white blood cell ), platelets * Ferritin, CPK (creatine phosphokinase ) * Electrolytes, creatinine, glycaemia * AST (aspartate aminotransferase ), ALT (alanine aminotransferase) , bilirubin, GGT (gamma-glutamyltransferase), alkaline phosphatase * Triglyceride, cholesterol * Haemostasis: APPT (activated partial thromboplastin time), PT (prothrombin time )

  6 months

Secondary Outcomes (6)

• Motor disability

  6 months

• Severity

  6 months

• Slow vital capacity (SVC)

  6 months

• Maximal inspiratory pressure (MIP)

  6 months

• Sniff nasal inspiratory pressure (SNIP)

  6 months

Study Arms (2)

MD1003

ACTIVE COMPARATOR

The investigational drug will consist in capsules of 100 mg biotin and excipients (lactose, magnesium stearate, croscarmellose sodium, Silica) tid during 12 months

Drug: MD1003

PLACEBO

PLACEBO COMPARATOR

This formulation consists in lactose powder and other excipients (magnesium stearate, croscarmellose sodium, Silica) as placebo, tid during 6 months and then switch to MD1003 tid during 6 additional months.

Drug: MD1003; Drug: Placebo oral capsule

Interventions

MD1003 DRUG

capsules 100mg 3 times per day

Also known as: BIOTIN

MD1003; PLACEBO

Placebo oral capsule DRUG

capsules 100mg lactose 3 times per day

PLACEBO

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 25 to 80 years, inclusive
• Male or female subjects with probable or confirmed ALS (revised international El Escorial criteria, Forbes et al., 2001).
• Patients presenting first motor deficits due to ALS for a maximum of three years at the first consultation in an ALS centre.
• Patients monitored for at least 6 months in an ALS centre or for whom the previous monitoring parameters are available (excepted for MIP and SNIP).
• Patients who have lost at least 5 points on the ALSFRS-R (ALS functional rating scale) during the last 12 months or at least 2 points during the preceding 6 months
• For patients with spinal form (onset of the disease affecting limbs) or respiratory form, slow vital capacity \> 60% of predicted value.
• Patients who are willing to give written consent (or oral consent in the presence of a trusted person if the patient is no longer able to write)
• Patients likely to be able to participate in all scheduled evaluation and complete all required study procedures (except for spirometry in bulbar patients with severe disability).

You may not qualify if:

• Patients on non-invasive ventilation for respiratory insufficiency due to ALS for more than 10 hours a day
• Patients who have lost less than 5 points on the ALSFRS-R during the last year or less than 2 points during the preceding 6 months
• Patients with a gastrostomy
• Patients who have lost more than 15% of their reference weight (defined as weight before disease onset)
• Patient with dyspnoea at rest or with the least effort (score \< 3 on the dyspnoea item of the ALSFRS-R)
• Patients with dementia
• Patient with severe or rapidly progressive form of ALS for whom the investigator estimates the life expectancy less than 3 months
• Patients with cancer, except basal cell carcinoma, for less than 5 years, or who require continuous treatment for cancer even if it is older
• Pregnant women.
• Subject who are not covered by a social security scheme.
• Subject under temporary or permanent Judicial Protection.
• Contraception: Both male subjects, 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.

Sponsors & Collaborators

• MedDay Pharmaceuticals SA: lead

Study Sites (1)

Hopital Gui De Chauliac

Montpellier, 34000, France

Location

Related Publications (1)

• Juntas-Morales R, Pageot N, Bendarraz A, Alphandery S, Sedel F, Seigle S, Camu W. High-dose pharmaceutical grade biotin (MD1003) in amyotrophic lateral sclerosis: A pilot study. EClinicalMedicine. 2020 Jan 27;19:100254. doi: 10.1016/j.eclinm.2019.100254. eCollection 2020 Feb.

  PMID: 32140672 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Biotin

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The primary objective of the study is to evaluate the safety of biotin at 300 mg/day over placebo in patients with amyotrophic lateral sclerosis. This is a 6-month double blind randomized 2:1 placebo-controlled study with two arms (placebo, biotin 300 mg/day). The study will be followed by a 6-month extension phase during which all patients will receive biotin 300 mg/day.

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 14, 2017
• Study Start: June 29, 2016
• Primary Completion: June 12, 2017
• Study Completion: December 1, 2017
• Last Updated: June 4, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)