NCT03691077

Effect of Ocrelizumab on Brain Innate Immune Microglial Cells Activation in MS Using PET-MRI With 18F-DPA714

A Prospective Study Evaluating the Effect of Ocrelizumab on Brain Innate Immune Microglial Cells Activation in Multiple Sclerosis Using PET-MRI With 18F-DPA714

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 51 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Ocrelizumab is a humanized anti-CD20 monoclonal antibody that showed in phase III trials a powerful effect on relapse rate and lesion load accumulation in the relapsing form of multiple sclerosis (RMS). This therapeutic agent also showed for the first time a significant reduction of disability progression in Primary Progressive Multiple Sclerosis (PPMS) patients, whereas all other anti-inflammatory drugs had failed to do so in well-conducted studies. This raises the possibility that ocrelizumab, beyond its effects on the adaptive immune system activation underlying white matter lesions and clinical relapses, could beneficially influence other mechanisms involved in the progressive phase of the disease, such as the innate immune microglial cells activation, that has been described to persist in a diffuse manner in the Central Nervous system (CNS). To date the activation of these cells is not accessible to classical Magnetic Resonance Imaging (MRI) techniques, impeding the full investigation of the therapeutic efficacy of drugs such as ocrelizumab.

Detailed description

The first dose of ocrelizumab will be administered as two 300-mg IV infusions (600 mg total) in 250 mL 0.9% sodium chloride each separated by 14 days (i.e., Days 1 and 15), followed by one 600-mg IV infusion in 500 mL 0.9% sodium chloride every subsequent doses (i.e., every 24 weeks) for 72 weeks. Premedication with 100 mg of methylprednisolone (or an equivalent) approximately 30 minutes prior to each ocrelizumab infusion and additional premedication with an antihistaminic drug (e.g., diphenhydramine) approximately 30 - 60 minutes before each infusion of ocrelizumab to reduce the frequency and severity of infusion-related reactions (IRRs). The addition of an antipyretic (e.g., acetaminophen/ paracetamol) may also be considered. Patients will undergo PET scan with 18F-DPA714 and MRI exams at different time points as mentioned in the assessment table. Disease will be clinically monitored at different time points with classical tests including EDSS, MSFC, BICAMS. Laboratory analyses on complete blood count, lymphocytes subsets count, neurofilament will be done. Analyses will not be limited to the above mentioned list. Pregnancy tests and genetics will be done. An optional lumbar puncture will be performed at baseline to assess cytokinic profile predictive of disease evolution and cortical pathology. Patients who refuse to have a lumbar puncture can be included in the clinical trial if they have eligibility criteria. TSPO polymorphism will be checked at baseline with other screening lab tests.

Conditions

• Multiple Sclerosis
• Relapse
• Primary Progressive Multiple Sclerosis

Interventions

Type	Name	Description
DRUG	Ocrelizumab	The first dose of ocrelizumab will be administered as two 300-mg IV infusions (600 mg total) in 250 mL 0.9% sodium chloride each separated by 14 days (i.e., Days 1 and 15), followed by one 600-mg IV infusion in 500 mL 0.9% sodium chloride every subsequent doses (i.e., every 24 weeks) for 72 weeks.

Timeline

• Start date: 2018-11-11
• Primary completion: 2024-05-01
• Completion: 2024-09-01
• First posted: 2018-10-01
• Last updated: 2023-09-06

Locations

1 site across 1 country: France