Evaluation of Safety and Efficacy of CLS12311 in Patients with Relapsing Remitting Multiple Sclerosis: A Phase Ib/IIa Multicenter Study
- Trial ID
- 2023-510127-30-00
- Protocol
- MSB-IG-H-2101
- Sponsor
- Cellerys AG
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicenter, Phase Ib/IIa study is to evaluate the **safety** and tolerability of CLS12311 in patients with **Relapsing Remitting Multiple Sclerosis (RRMS)**. Additionally, the study aims to provide proof-of-concept for the efficacy of CLS12311 in reducing the number of new lesions on brain magnetic resonance imaging (MRI), which serves as a measure of inflammatory disease activity in RRMS patients. This is clinically relevant as it addresses both the safety profile and potential therapeutic benefits of CLS12311, which could lead to improved management of RRMS.
Secondary objectives include:
- Assessing the safety and tolerability of each dose group of CLS12311.
- Defining the optimal dose of CLS12311 to reduce new disease activity on brain MRI in RRMS patients.
- Exploring the mechanisms of action of tolerance induction with peptide-coupled red blood cells (RBCs) and identifying biomarkers for measuring immune tolerance induction.
Participants
The clinical trial involves a total of **16 participants** diagnosed with **Relapsing Remitting Multiple Sclerosis (RRMS)**. The study population comprises both male and female subjects, aged between **18 to 55 years**, who meet the 2017 McDonald criteria for RRMS. Participants were selected based on specific inclusion criteria, including a disease duration of less than 10 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 5.5 at baseline. The trial includes individuals who have experienced at least one relapse or new contrast-enhancing lesion in the previous 12 months. Participants are either untreated or have been off therapy for specified periods and have chosen not to receive approved therapies after being informed by investigators. Lifestyle considerations include the requirement for sexually active female participants of childbearing potential to use a highly effective method of contraception, and male participants to use condoms unless surgically sterile. All participants must have basic immunization against SARS-CoV-2. The trial does not specifically exclude vulnerable populations, indicating a broad inclusion approach within the defined criteria.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and **efficacy** of the investigational product, CLS12311, in patients with **Relapsing Remitting Multiple Sclerosis (RRMS)**. This study is structured as a multicenter, Phase Ib/IIa trial, employing a randomized, double-blind, controlled design. The trial is expected to commence recruitment in June 2024 and conclude by March 2027, with the overall duration of participant involvement estimated to span several months, depending on individual response and adherence to the protocol.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, disease duration, and baseline **Expanded Disability Status Scale (EDSS)** scores. Following successful screening, participants will enter the baseline period, during which specific qualification criteria, including the presence of new brain lesions on MRI, will be evaluated. The treatment phase will involve regular follow-up visits to monitor safety and efficacy endpoints, including the number and severity of treatment-emergent adverse events (TEAEs) and the cumulative number of new brain lesions on MRI scans. The end-of-study visit will occur after the completion of the treatment phase, where final assessments will be conducted to evaluate the overall impact of the investigational product.
Participants are expected to remain in the study for the entire duration unless specific conditions necessitate early termination. Such conditions may include the occurrence of severe adverse events, non-compliance with study procedures, or withdrawal of consent. The trial's integrated design allows for a seamless transition from Phase I, focusing on safety and tolerability, to Phase II, which aims to gather additional safety and efficacy data. This approach enhances the efficiency of the investigational product's development, providing valuable insights into its potential therapeutic benefits for patients with RRMS.
Treatment
The clinical trial involves the administration of **CLS12311**, an experimental medication developed by CELLERYS AG. This investigational product is a **dispersion for infusion** and is administered via the **intravenous** route. The active substance, also named CLS12311, is classified as a structurally diverse substance used in **cell therapy**. The primary objective of the trial is to assess the safety and efficacy of CLS12311 in patients with **Relapsing Remitting Multiple Sclerosis (RRMS)**. The dosing schedule and frequency of administration are determined by the study protocol, and participant compliance is monitored throughout the trial to ensure adherence to the treatment regimen.
In addition to the experimental treatment, the study also involves the use of **autologous uncoupled red blood cells (RBCs)**. This component is not associated with a specific pharmaceutical form or active substance name, and it serves as a comparator treatment within the trial. The role of the autologous uncoupled RBCs is to provide a baseline for evaluating the effects of the experimental medication. The administration details and monitoring procedures for this component are aligned with the study's design to ensure the integrity of the trial results.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the impact of the investigational product, **CLS12311**, on reducing the number of new brain lesions in patients with Relapsing Remitting Multiple Sclerosis (RRMS). The primary efficacy endpoint for Part B of the study is the cumulative number of new brain lesions observed on magnetic resonance imaging (MRI) scans during the treatment phase, specifically between weeks 16 and 24, compared to the pre-treatment phase from weeks -8 to 0. New lesions are defined as contrast-enhancing lesions on the reference scan at weeks -8 and 16 or new/enlarging T2 lesions on scans at week 0 compared to week -8, and at week 24 compared to week 16. MRI assessments will be conducted centrally by independent readers to ensure objectivity and consistency.
Secondary efficacy endpoints include the number of new lesions on brain MRI in weeks 16-24 across three dose groups and the efficacy of **CLS12311** in reducing new brain MRI lesions in defined subgroups, such as those stratified by HLA or immunological parameters. Exploratory endpoints will involve immunological and biomarker measures, including the percentage of patients in each dose group showing a reduction of antigen-specific T cells and changes in predefined serum biomarkers of disease activity. Mechanistic profiling of serum and blood cells will also be performed, utilizing broad-based methods such as multi-analyte measurements, transcriptomics, and proteomics to assess biomarkers of tolerance, tissue damage, and inflammation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: RRMS according to the 2017 McDonald criteria
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Male or female patients (assigned at birth) aged 18-55 years
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Disease duration (since diagnosis) <10 years
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: EDSS at baseline 0-5.5
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Untreated patients or patients being off therapy for the time periods mentioned under exclusion criterion No. 2. Patients are either not eligible to receive approved therapies or have explicitly chosen not to receive such therapies after being adequately informed by the investigators
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Only for sexually active female patients of childbearing potential (sexually mature, pre-menopausal and not surgically sterile): the patient is willing to use a highly effective method of contraception (defined in the study protocol) throughout the complete treatment phase or at least for 4 weeks after the last dose of CLS12311
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Male patients willing to use contraception (condoms) throughout the complete treatment phase or at least for 4 weeks after the last dose of CLS12311 unless surgically sterile
- [General inclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Basic immunization against SARS-CoV-2, i.e. both doses of two-dose vaccines (or one dose of a vaccine and a SARS-CoV-2 infection before or after vaccination) OR a dose of a single-dose vaccine
Exclusion Criteria
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: 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)
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: 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 exclusion criterion No. 18); e. siponimod, ponesimod within 8 weeks prior to screening visit 1, provided normal lymphocyte counts (see exclusion criterion No. 18); 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
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of HIV, chronic or active Hepatitis C, chronic or active Hepatitis B or prior Syphilis, which has not been sufficiently treated
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Long-COVID19 Syndrome
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of splenectomy or chronic liver disease
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of coronary artery disease, chronic heart failure, aortic stenosis
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Current anticoagulation therapy
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Uncontrolled grade II hypertension (≥160 systolic and/or ≥100 diastolic blood pressure; according to ISH global practice guidelines) despite treatment or without treatment
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of stroke
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Pregnant female confirmed by a positive pregnancy test or breastfeeding
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of alcohol or drug abuse within the 1 year prior to screening visit 1
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of or existing malignancy within the last 5 years prior to enrolment except history of basal cell carcinoma and melanoma in situ
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of or existing relevant central nervous system disorder (other than MS)
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Allergy to gadolinium-based contrast agents
- [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: 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 baseline period)]: Anemia, defined as hemoglobin levels ≤12.5 g/dl (7.25 mmol/l) for female and ≤13.5 g/dl (8.37 mmol/l) for male participants (may be repeated if 11.5 -12.5 g/dl in females and 12.5 - 13.5 g/dl in males)
- [Specific exclusion criteria (to be assessed during the baseline period)]: Erythrocyte count 3.8 E12/L in female and >4.3 E12/L in male)
- [Specific exclusion criteria (to be assessed during the baseline period)]: Lymphopenia with total lymphocyte counts ≤ 1000/µl (may be repeated if >800/µl)
- [Specific exclusion criteria (to be assessed during the baseline period)]: Positive HIV testing
- [Specific exclusion criteria (to be assessed during the baseline period)]: Positive results of screening period testing for serological markers for hepatitis B, C, and Syphilis indicating acute or chronic infection
- [Specific exclusion criteria (to be assessed during the baseline period)]: Positive results of screening period testing for serological markers for hepatitis B, C, and Syphilis indicating acute or chronic infection
- [Specific exclusion criteria (to be assessed during the baseline period)]: Having one or more of the following laboratory results: a. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (may be repeated if eGFR is 45-59 mL/min/1.73 m2); b. ALT or AST > 3 x upper limit of normal (ULN; may be repeated if 3.1-4 x ULN); c. Total bilirubin greater than 2 x ULN (may be repeated if 2.1 - 3 x ULN), with the exception for patients with Gilbert's disease; d. Platelet count ≤ 100E9/L (may be repeated if 80-100E9/L); e. Abnormalities in hepatic synthetic function tests (PT time, INR, PTT, albumin) as judged by the Investigator to be clinically significant
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 01 Jun 2024 | 4 |
 Germany | Not Recruiting | 01 Jun 2024 | 4 |
 Italy | Not Recruiting | 01 Jun 2024 | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Autologous uncoupled red blood cellsRBCs | Placebo | N/A | — | — | — | N/A |