A Clinical Trial Examining the Effects of Temelimab Following Rituximab Treatment in Patients with Multiple Sclerosis

Phase 1

• Conditions: Multiple Sclerosis; MedDRA version: 21.0Level: PTClassification code 10080700Term: Relapsing multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-004822-15-SE
• Lead Sponsor: GeNeuro Innovation SAS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-01-17
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. The subject has given written informed consent to participate in the study
2. Current diagnosis of RMS, based on the McDonald 2017 criteria
3. Having received treatment with rituximab, as per local clinical routine for at least 12 months prior to the Screening Visit
4. Having received their last dose of rituximab not more than 8 weeks and not less than 4 weeks before Randomization (Study Day 1)
5. Having B-cell count < Lower limit of detection (LLOD) (<0.01*10-9 CD19+ cells/ L)
6. Having expanded disability status scale (EDSS) 2.5 – 5.5 inclusive at Baseline
7. Present clinical worsening in one or more neurological domains as assessed by EDSS, ambulatory function as assessed by 6MWT or T25FW, cognitive functioning as assessed by SDMT or increased need of walking aids or pharmacological/procedures for bowel and bladder functions over the last year.
8. Brain Magnetic resonance imaging (MRI), lesion burden with >9 T2 cerebral lesions (assessed within the last 24 months)
9. Stable clinical presentation of MS for 30 days prior to Screening e.g. no relapse, no acute neurological exacerbation.
10. Age range from 18 to 55 years (both inclusive)
11. Body weight between 40 – 100 kg (both ranges are inclusive)
12. No disease modifying therapies (DMTs) other than rituximab, within 12 months of Screening
13. No contraindication to Biomarker assessments: brain Magnetic resonance imaging (MRI), blood/serum collection and cerebrospinal fluid (CSF) collection
14. Agreeing to undergo two lumbar puncture
15. Be willing and able to follow all study procedures and assessments according to the study protocol
16. Female patients of childbearing potential (FPCBP) or procreative male patients (PMP), willing to use highly effective contraceptive methods throughout the study duration and at least until 5 months after the last study treatment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Current diagnosis of primary progressive MS (PPMS)
2. Any disease other than MS (e.g. myelitis and /or bilateral optic neuritis) that could better explain the patient’s signs and symptoms
3. Usage of any of the following medications prior to the Screening visit:
a) Any usage of interferon beta, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide within 12 months prior to Screening,
b) Any history of exposure to mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation at any time,
c) Any usage of natalizumab within 24 months prior to Screening,
d) Any usage of highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine within 12 months prior to Screening,
e) Any usage of any experimental treatment if not washed out for = 5 half-lives or = 12 months (whichever is longer), except rituximab which is allowed before the study.
4. CTCAE Grade 2 or greater lymphopenia
5. Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including:
a) Diagnosis or history of schizophrenia
b) Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation
c) Current or past (within the last 2 years) alcohol or drug abuse
6. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (NYHA class 3 or 4)
7. Known inability to undergo an MRI scan
8. Contraindications to the use of glucose 5% infusion
9. Inability to follow study instructions, or complete study assessments, as defined by the protocol
10. Any history of cancer with the exceptions of basal cell carcinoma and/or carcinoma in situ of the cervix, and only if successfully treated by complete surgical resection, with documented clean margins and any medically unstable condition as determined by the investigator
11. Legal incapacity or limited legal capacity
12. Pregnant or breastfeeding women
13. History of, or positive serology for viral hepatitis B not explained by vaccination
14. History of, or positive serology for viral hepatitis C or human immunodeficiency virus (HIV) at any time
15. Abnormal liver function tests: AST or ALT > 2 times upper limit of normal range (ULN), or conjugated bilirubin > 2 times ULN, or AP or GGT > 3 times ULN
16. Positive pregnancy test at any time

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified