NA

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2017-004158-40-FR
• Date of registration: 04/07/2018
• Prospective Registration: Yes
• Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
• Public title: NA
• Scientific title: A Prospective study evaluating the effect of ocrelizumab on brain innate immune Microglial cells Activation in Multiple Sclerosis using PET-MRI with 18F-DPA714 - INN-MS
• Date of first enrolment: 11/09/2018
• Target sample size: 71
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004158-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Longitudinal study; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: DRCI Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

• Name: DRCI Hôpital St Louis
• Affiliation: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria for all MS subgroups:
1. Signed informed consent form
2. Able to comply with the study protocol, in the investigator's judgment
3. Social security registration
4. Age 18 - 60 years, inclusive
5. For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 12 months after the last dose of study drug.
- Inclusion criteria specific for the RMS subgroups:
RMS patients with a remitting-relapsing course (n=17)
1. Have a definite diagnosis of RMS, confirmed as per the revised McDonald 2010 criteria ;
2. Absence of history of Secondary Progressive Multiple Sclerosis (SPMS) or history of Primary Progressive Multiple Sclerosis (PPMS)
3. Have an active disease: Activity determined by clinical relapses and/or MRI activity
4. Neurological stability for >/= 30 days prior to both screening and baseline
5. EDSS of 0.0 to 5.5, inclusive, at screening
6. Have a length of disease duration, from first symptom, of < 15 years
7. Have received no more than first line injectable treatments (i.e. IFNs and GA, possible switchs within this class) + 1 other treatment (e.g. teriflunomide, DMF, fingolimod, natalizumab, no switch allowed within this group).
8. Have a suboptimal response to the last received DMT: a suboptimal response is defined by having at least one of the following events while being on a stable dose of the same DMT for at least 6 months:
a. One or more clinically reported relapse(s)
b. OR one or more T1 Gd-enhanced lesion(s)
c. OR one or more new and/or enlarging T2 lesions on MRI
9. In addition, in patients receiving stable doses of the same approved DMT for more than a year, at least one of the above events must have occurred within the last 12 months of treatment with this DMT.
RMS patients having reached a secondary progressive phase (n=17)
1. Diagnosis of SPMS according to Lublin et al. 2014 criteria
2. Prior history of RRMS (Have a definite diagnosis of RRMS, confirmed as per the revised McDonald 2010 criteria)
3. Evidence of any disability progression unrelated to relapse within the 2 year period prior to study baseline. Progression in the last year will be reported by the treating physician and documented using a disease progression rating system checklist
4. Progression is defined as steadily increasing objectively documented neurologic dysfunction/disability without unequivocal recovery
5. Absence of history of Primary Progressive Multiple Sclerosis or Progressive Relapsing Multiple Sclerosis at screening
6. EDSS at screening 7. Score of >/= 2.0 on the Functional Systems (FS) scale for the pyramidal system that is due to lower extremity findings
8. Disease duration from the onset of Secondary Progressive MS symptoms of less than 10 years if baseline EDSS 9. Disease duration from the onset of Secondary Progressive MS symptoms of less than 15 years if baseline EDSS > 5
10. Have received no more than
Exclusion criteria:
- For all MS subgroups:
1. Inability to complete an MRI
2. Impossibility to complete a PET scan
3. Known presence of other neurological disorders, including but not limited to, the following:
a. History of ischemic cerebrovascular disorders or ischemia of the spinal cord
b. History or known presence of CNS or spinal cord tumor
c. History or known presence of potential metabolic causes of myelopathy
d. History or known presence of infectious causes of myelopathy
e. History of genetically inherited progressive CNS degenerative disorder
f. Neuromyelitis optica
g. History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease
h. History or known presence of sarcoidosis
i. History of severe, clinically significant brain or spinal cord trauma
- General Health:
1. Pregnancy or lactation
2. Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressant drugs during the course of the study
3. History or currently active primary or secondary immunodeficiency
4. Lack of peripheral venous access
5. Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal or any other significant disease that may preclude patient from participating in the study
6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
7. Congestive heart failure
8. Known active bacterial, viral, fungal, mycobacterial infection or other infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit
9. History or known presence of recurrent or chronic infection
10. History of malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been previously completely excised
11. History of alcohol or drug abuse within 24 weeks prior to baseline
12. History or laboratory evidence of coagulation disorders
13. History of major opportunistic infections
14. History of recurrent aspiration pneumonia requiring antibiotic therapy
15. Hypersensitivity to the active substance or to any of the excipients
- Laboratory Findings:
1. TSPO polymorphism indicating a low affinity profile
2. Positive serum B human chorionic gonadotropin measured at screening and before each PET-Scan procedure
3. Positive screening tests for hepatitis B or hepatitis C
4. Lymphocyte count below lower limit of normal
5. CD4 count <300/µL
6. Absolute neutrophil count <1.0×103/µL
- Medications:
1. Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit
2. Treatment with any

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Relapsing MS or primary progressive MS
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Ocrevus
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
Other descriptive name: ocrelizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Main Objective: Determine if ocrelizumab treatment is associated with a decrease in the extent of brain white matter microglial activation.

Secondary Objective: Secondary objectives will assess the decrease of microglial activation as measured by [18F]DPA-714 PET expressed as percentage of activated voxels in key regions of interest relevant for MS progression.

Primary end point(s): Percent change in the extent of 18FDPA714 positive voxels in the total white matter from baseline to month 24 in the whole cohort of MS patients.

Timepoint(s) of evaluation of this end point: 24 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 6 and 24 months

Secondary end point(s): - Percent change in extent of 18FDPA714 positive voxels in normal appearing white matter between baseline and months 6 (short-term) and 24 (long-term) in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort
- Percent change in extent of 18FDPA714 positive voxels in the total white matter from baseline to month 6 in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.
- Percent change in extent of [18F]-DPA-714 positive voxels in the total white matter from baseline to month 24, in PPMS cohort and in RMS cohort (whole cohort and subgroups of RRMS and SPMS patients).
- Percent change in extent of 18FDPA714 positive voxels in white matter lesions between baseline to months 6 and 24, in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.
- Percent change in extent of 18FDPA714 positive voxels in white matter perilesional areas between baseline to months 6 and 24 in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.
- Percent change in number of plaques classified as chronic active from baseline to month 6 and month 24 in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.
- Percent change in number of plaques classified as smoldering plaques from baseline to month 6 and month 24 in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.
- Percent change in extent of 18FDPA714 positive voxels in deep grey matter between baseline to months 6 and 24 in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.
- Percent change in extent of 18FDPA714 positive voxels in cortical grey matter between baseline to months 6 and 24 in the whole cohort, in RMS cohort (global and splitted in RRMS and RMS having reached the SPMS phase) and in PPMS cohort.

Secondary ID(s)

P170702J

Source(s) of Monetary Support

ROCHE

Ethics review

Status: Approved
Approval date:
Contact: