Testing a new treatment for multiple sclerosis using a brain protein target

An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis

This study is testing if two new drugs can help change the way immune cells behave in people with secondary progressive multiple sclerosis by targeting a specific brain protein.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 35 Years to 65 Years
• Sex: All
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: Alemtuzumab
• Locations: 1 site (London, England)
• Trial ID: NCT03850301 on ClinicalTrials.gov

What this trial studies

This study aims to validate the 18 kiloDalton Translocator Protein (TSPO) as a novel target for neuroimmunomodulation in patients with secondary progressive multiple sclerosis (SPMS). Researchers will investigate the effects of two drugs, etifoxine and XBD173, which bind to TSPO, on immune responses in SPMS patients. The study will involve blood tests and comparisons with healthy volunteers to assess how these drugs influence immune cell behavior. The primary goal is to determine whether TSPO ligand binding can shift immune cells towards a reparative phenotype.

Who should consider this trial

Good fit: Ideal candidates are adults aged 35-65 with a diagnosis of secondary progressive multiple sclerosis and an Expanded Disability Status Scale (EDSS) score between 3.5 and 6.5.

Not a fit: Patients with active neurological diseases other than multiple sclerosis or those with significant abnormalities in routine blood tests may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new therapeutic options for managing secondary progressive multiple sclerosis.

How similar studies have performed: While the approach of targeting TSPO is novel, preclinical studies suggest potential benefits, but human trials specifically targeting this pathway in MS are limited.

Eligibility criteria

Inclusion Criteria:

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
2. Aged 35-65 years old
3. A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods listed below
4. Male subject must agree to use one of the contraception methods listed above.
5. Willing to abstain from alcohol for the duration of dosing.
6. Expanded Disability Status Scale (EDSS) \>3.5 \<6.5 (SPMS patients only)

Exclusion Criteria:

1. History of active neurological disease other than migraine or MS
2. Clinically meaningful abnormalities in routine bloods including:

   * eGFR \< 60ml/min
   * Elevation of liver enzymes/bilirubin
   * Prolonged prothrombin time
   * Thrombocytopenia
3. Use of the following medications or therapies:

   * Immunosuppressive or immunomodulatory drugs within the last 6 months
   * Alemtuzumab or haematopeotic stem cell therapy
   * Central nervous system depressants (including opioid analgesics, barbiturates, sleeping pills, antihistamines, antipsychotics)
   * P450 CY3A4 inducers or inhibitors
   * oral contraceptives
   * oral anticoagulants or antiplatelet agents other than low dose aspirin
   * levothyroxine
4. Currently breastfeeding
5. Any clinical significant medical conditions that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures.
6. History of any clinical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study, such as some chronic systemic diseases affecting blood, liver or kidneys or endocrine system
7. Unwillingness or inability to follow the procedures outlined in the protocol
8. Subject is mentally or legally incapacitated
9. Contraindication to XBD173 use:

   • Hypersensitivity to the active substance or to any of the excipients
10. Contraindication to etifoxine use:

    * Myasthenia gravis
    * syndromes of glucose and galactose malabsorption or lactose deficiency

Where this trial is running

London, England

• Imperial College Healthcare NHS Trust — London, England, United Kingdom (Recruiting)

Study contacts

• Study coordinator: David Owen, PhD

Conditions Multiple Sclerosis