Relapsing Remitting Multiple Sclerosis (RRMS) MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: CLS12311
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: not applicable
Current Sponsor code: CLS12311
Other descriptive name: Peptid coupled red blood cells
Concentrat
Sponsors
Cellerys AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A and Part B General inclusion criteria (to be assessed at the beginning of the screening period based on patient interview and medical history): 1. RRMS according to the 2017 McDonald criteria 2. Age 18-55 years 3. Disease duration (since diagnosis) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Part A and B General exclusion criteria (to be assessed at the beginning of the screening period based on patient interview and medical history): 1. Patients with an active chronic disease (or stable but treated with immunomodulatory/-suppressive therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Crohn’s disease, ulcerative colitis, etc.) or with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug-induced immune deficiency) 2. Prior treatment with any of the medications below within the specified time-frame: a. glatiramer acetate, interferon-beta within 4 weeks prior to screening visit 1 b. dimethylfumarate, diroximel-fumarate within 4 weeks prior to screening visit 1 c. teriflunomide within 4 weeks prior to screening visit 1, provided accelerated elimination procedure (eg. cholestyramine) was performed and teriflunomide plasma level are below 0.02 mg/L before randomization d. fingolimod, ozanimod within 12 weeks prior to screening visit 1, provided normal lymphocyte counts (see inclusion criterion No. 16) e. siponimod, ponesimod within 4 weeks prior to screening visit 1, provided normal lymphocyte counts (see inclusion criterion No. 16) f. natalizumab within 12 weeks prior to screening visit 1 g. ocrelizumab, ofatumumab, rituximab, alemtuzumab, cladribine, mitoxantrone within 52 weeks prior to screening visit 1 h. plasma exchange, intravenous immunoglobulin within 8 weeks prior to screening visit 1 i. azathioprine, methotrexate, cyclophosphamide or any other continuous immunosuppressive therapy within 24 weeks prior to screening visit 1 j. any other immunosuppressive monoclonal antibody treatment within 24 weeks prior to screening visit 1 k. Prior autologous hematopoietic stem cell transplantation l. Corticosteroid treatment for MS relapse within 4 weeks prior to screening visit 1 m. Patients who participated in the ETIMSred trial (patients who have participated in the ETIMSred trial may be incuded in Part A) 3. History of HIV, chronic or active Hepatitis C, chronic or active Hepatitis B or prior Syphilis, which has not been sufficiently treated 4. Long-COVID19 Syndrome 5. History of splenectomy or chronic liver disease 6. History of coronary artery disease, chronic heart failure, aortic stenosis 7. Current anticoagulation therapy 8. Uncontrolled grade II hypertension (=160 systolic and/or =100 diastolic blood pressure; according to ISH global practice guidelines) despite treatment or without treatment 9. History of stroke 10. Pregnant female confirmed by a positive pregnancy test or breast-feeding 11. History of alcohol or drug abuse within the 1 year prior to screening visit 1 12. History of or existing malignancy within the last 5 years prior to enrolment except history of basal cell carcinoma and melanoma in situ 13. History of or existing relevant central nervous system disorder (other than MS) 14. Allergy to gadolinium-based contrast agents 15. Any other disease or condition, which could interfere with the participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures Specific exclusion criteria (to be assessed during the screening period): 16. Anemia, defined as hemoglobin levels =125 g/dl (7.25 mmol/l) for female and =135 g/dl (8.37 mmol/l) for male participants (may be repeated if 115 -125 g/dl in females and 125 - 135 g/dl in males) 17. Erythrocyte count <4.0 G/l in female and <4.5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety objective (Part A and B) To assess the safety and tolerability of CLS12311 in patients with RRMS Efficacy objective (Part B) To provide proof-of-concept for the efficacy of CLS12311 in reducing the number of new lesions on brain magnetic resonance imaging (MRI) as a measure for inflammatory disease activity in patients with RRMS;Secondary Objective: Safety objectives (Part A and B) To assess the safety and tolerability of each dose group of CLS12311 Efficacy objective (Part B) To define the optimal dose of CLS12311 to reduce new disease activity on brain MRI in RRMS patients Exploratory objective (Part A and B) To understand the mechanism/s of action of tolerance induction with peptide-coupled RBCs and to identify biomarkers for measuring immune tolerance induction;Primary end point(s): Safety (Part A and B) • Safety and tolerability of CLS12311 measured by the number and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) and/or worsening of disease by clinical (relapses) and imaging (number and size of brain lesions) Efficacy (Part B only) • The cumulative number of new brain lesions on the MRI scans developed in the post-treatment phase between weeks 16 and 24 compared to the pre-treatment number of new brain MRI lesions developed between weeks -8 and 0 for any dose. New lesions on brain MRI are defined as being: • Contrast enhancing lesions on the reference scan at weeks -8 and 16 or • new/enlarging T2 lesions on scan at: • week 0 compared to scan at week -8 • week 24 compared to scan at week 16 MRIs will be assessed centrally by independent readers.;Timepoint(s) of evaluation of this end point: At the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety endpoints (Part A and B): • Number and severity of TEAEs and TESAEs in each dose group • Number of confirmed relapses in the treatment phase in each dose group • Changes in clinical measures of disease severity (EDSS, 9-HPT, T25FWT, SDMT) following CLS12311 administration in each dose group (Part A only EDSS) Efficacy endpoints (Part B): • Number of new lesions on brain MRI (as defined above) in weeks 16-24 in the three dose groups • Efficacy of CLS12311 in reducing the number of new brain MRI lesions (as defined above) in defined subgroups, e.g. stratified for HLA or immunological parameters Exploratory immunological and biomarker measures (Part A and B): • Percentage of patients in each dose group showing a reduction of antigen-specific T cells against the protein(s) they responded to at study entry • Changes in predefined serum biomarkers of disease activity and in other markers related to tolerance induction • Mechanistic profiling of serum and blood cells will be performed by measuring specific biomarkers of tolerance, tissue damage and inflammation as well as broad-based methods including but not limited to multi-analyte measurements, transcriptomics and proteomics.;Timepoint(s) of evaluation of this end point: At the end of the trial | — |
Countries
Czechia, Czech Republic, Germany, Italy, Switzerland
Contacts
Public ContactAdministrative Office
Cellerys AG
Outcome results
None listed