Ulipristal Acetate In Disease Charcot-Marie-Tooth Type of 1A (UPACOMT)

LONG-TERM EFFECTS TOLERANCE AND THE Ulipristal Acetate IN DISEASE Charcot-MARIE-TOOTH TYPE OF 1A

The disease Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy, for which no treatment has proved its effectiveness. It is autosomal dominant, associated with a duplication of the chromosome 17p11.2 region which leads to overexpression of the gene and the protein-peripheral myelin protein-22 (PMP22), a major component of peripheral myelin.

In animals and humans, PMP22 mRNA level of glutathione S-transferase theta 2 and Cathepsin A (markers of oxidative stress), detected in a skin biopsy are markers that may play a role in the prognosis evolution of the disease. Furthermore, several studies have shown that the administration of progesterone increased the expression of PMP22 gene (measured in a skin biopsy) and worsening symptoms. In contrast, anti-progestins reduce the synthesis of PMP22 and improve symptoms in rat CMT1A.

The long-term safety of anti-progesterone was evaluated for mifepristone (RU486) ulipristal acetate and (EllaOne®). Few side effects have been reported including a few cases of endometrial hyperplasia reversible upon discontinuation of treatment. With the RU486, rare cases of adrenal androgen and failure have been observed. However, EllaOne® has low antagonistic action on the glucocorticoid receptor and no action on androgen receptors. The investigators therefore believe that it will be well tolerated in humans and will reduce the synthesis of PMP22 and the action of oxidative stress by improving disability of patients.

Study Overview

• Status: Terminated
• Conditions: CMT1A
• Intervention / Treatment: Drug: EllaOne; Drug: EllaOne placebo

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25030
    • Service d'Explorations et pathologies neuro- musculaires
  • Dijon, France, 21079
    • Département de Neurologie
  • Nancy, France, 54035
    • Département de Neurologie
  • Paris, France, 75561
    • Unité de pathologie neuro-musculaire
  • Strasbourg, France, 67098
    • Département de Neurologie Centre de Référence des Maladies Neuromusculaires Grand Est (CERNEST) Hôpital de Hautepierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male 18-70 years
• CMT1A proven genetically (17p11.2 duplication)
• symptomatic CMT1A (MRC score <5 in at least one muscle group)
• Non severe axonal impairment (amplitude of the motor evoked potential on the median nerve and / or ulnar than 50% of normal)
• Subject contacted with a valid phone number
• Subject affiliated to a social security scheme
• Subject has been informed of the results of the medical examination prior

Exclusion Criteria:

• Another cause of neuropathy: Chronic alcohol intoxication, chemotherapy, diabetes, kidney failure, monoclonal gammopathy, cryoglobulin, B12 deficiency, hepatitis B / C, HIV, Lyme or poliomyelitis
• Liver failure
• Lapp lactase deficiency, malabsoprtion syndrome glucose / galactose
• Support long-term drug interacting with the CYP3A4
• Patients with indication against xylocaine adrenaline
• In the biopsy site: surgery, skin disease or local infection
• Immunosuppression innate or acquired
• Hypersensitivity to the active substance / excipient
• uncontrolled severe asthma
• Treatment with vitamin C or vitamin B3 in the four weeks preceding randomization
• Orthopaedic surgery of the lower limbs in the 6 months prior to randomization or planned
• Against indication xylocaine adrenaline
• Malfunction of the innate or acquired coagulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Arm (1) will be randomised to receive either : 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.	Drug: EllaOne; 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.; Other Names: 1: Experimental; 2: Experimental; 3: Experimental; Drug: EllaOne placebo; 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.; Other Names: 1: Experimental; 2: Experimental; 3: Experimental
Experimental: 2; Arm (2) will be randomised to receive either : 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.	Drug: EllaOne; 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.; Other Names: 1: Experimental; 2: Experimental; 3: Experimental; Drug: EllaOne placebo; 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.; Other Names: 1: Experimental; 2: Experimental; 3: Experimental
Experimental: 3; Arm (3) will be randomised to receive either : 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.	Drug: EllaOne; 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.; Other Names: 1: Experimental; 2: Experimental; 3: Experimental; Drug: EllaOne placebo; 5 mg/per os of EllaOne every day through 12 months.; 10 mg/per os of EllaOne every day through 12 months.; EllaOne placebo/per os every day through 12 months.; Other Names: 1: Experimental; 2: Experimental; 3: Experimental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Analysis of the effectiveness of Ellaone. This will be assessed by the production of RNA PMP22 using skin biopsy.	12 months after treatment with EllaOne

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Study Director: Andoni Echaniz-Laguna, MD, University Hospital, Strasbourg, france

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2015
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 2, 2017

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 9, 2015

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Neurology; Physical medicine and rehabilitation
• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Nerve Compression Syndromes; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy
• Other Study ID Numbers: 6100

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No