Relapsing-remitting Multiple Sclerosis (RRMS)
Conditions
Brief summary
RED4MS is a clinical trial to assess the safety and tolerability of autologous peptide coupled red blood cells (CLS12311) in patients with relapsing remitting multiple sclerosis (RRMS). CLS12311 consists of autologous red blood cells (RBCs) coupled with antigenic peptides and aims to treat RRMS by induction of antigen-specific immune tolerance.
Detailed description
The RED4MS trial is designed as an open-label, dose-escalation phase Ib study, enrolling 9 RRMS patients in three ascending dose groups. The first patient (sentinel) in each dose group will receive one cycle of the therapy, while the remaining patients will receive two treatment cycles.
Interventions
DRUGCLS12311 low
Peptide-coupled Red Blood Cells (RBCs)
DRUGCLS12311 medium
Peptide-coupled Red Blood Cells (RBCs)
DRUGCLS12311 high
Peptide-coupled Red Blood Cells (RBCs)
DRUGuncoupled RBCs
autologous Red Blood Cells (RBCs)
Sponsors
Cellerys AG
Novartis
Scope International AG
Tetec AG
Jung Diagnostics GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Individual patients will be assigned to three dose groups. Patients will be allocated in the low, medium, high dose group according to the order of recruitment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. RRMS according to the 2017 McDonald criteria 2. Male or female patients (assigned at birth) aged 18-55 years inclusive 3. Disease duration (since diagnosis) \<10 years 4. Expanded Disability Status Scale (EDSS) at baseline 0-5.5 5. Untreated patients or patients being off therapy for the time-periods listed 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 6. Only for 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 throughout the treatment phase or at least for 4 weeks after the last dose of the study drug 7. Male patients willing to use contraception (such as a condoms) throughout the treatment phase or at least for 4 weeks after the last dose of the study drug, unless surgically steril
Exclusion criteria
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 specified in the protocol 3. History of HIV, chronic or active Hepatitis, chronic or active Hepatitis B or Syphilis 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 the International Society of Hypertension (ISH) 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. 16. 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) 17. Erythrocyte count \<4.0 E12/L in female and \<4.5 E12/L in male patients (may be repeated if \>3.8 E12/L in female and \>4.3 E12/L in male) 18. Lymphopenia with total lymphocyte counts ≤1000/µl (may be repeated if \>800/µl) 19. Positive HIV testing 20. Positive results of baseline period testing for serological markers for hepatitis B, C, and Syphilis indicating acute or chronic infection 21. Patient is not eligible for blood donation according to local regulations 22. Having one or more of the following laboratory results: 1. Estimated glomerular filtration rate (eGFR)\< 60 mL/min/1.73 m2 (may be repeated if eGFR 45-59 mL/min/1.73 m2) 2. ALT or AST \>3x upper limit of normal (ULN; may be repeated if 3.1-4x ULN) 3. Total bilirubin greater than 2x ULN (may be repeated if 2.1-3x ULN), with the exception for patients with Gilbert's disease 4. Platelet count ≤100x109/L (may be repeated if 80-100x 109/L) 5. Abnormalities in hepatic synthetic function tests as judged by the Investigator to be clinically significant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety of CLS12311] | From first blood donation for CLS12311 production through Week 48 (end of study) | Number of treatment-emergent adverse events (TEAEs) during the treatment and safety follow-up period. TEAEs were defined as adverse events with first onset or worsening after the first blood donation for CLS12311 production and were graded according to CTCAE v4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Related TEAEs in Each Dose Group [Safety of CLS12311] | From first blood donation for CLS12311 production through Week 48 (end of study) | Number of treatment-related treatment-emergent adverse events (TEAEs) during the treatment and safety follow-up period. TEAEs were defined as adverse events with first onset or worsening after the first blood donation for CLS12311 production, considered related to study treatment or blood donation, and graded according to CTCAE v4.0. |
| Number of Patients With Confirmed MS Relapse in Each Dose Group [Safety of CLS12311] | From baseline through Week 48 (end of study) | Number of patients with a centrally confirmed multiple sclerosis relapse in each dose group during the study period. Relapse was assessed according to protocol criteria as new or worsening neurological symptoms lasting at least 24 hours in the absence of fever or infection and confirmed by central neurological review. |
| Change in Number of New or Enlarging T2 Lesions on Brain MRI in Each Dose Group [Safety of CLS12311] | Baseline to Week 48 (end of study) | Change from baseline to Week 48 in the number of contrast-enhancing lesions (CEL) and new or enlarging T2 lesions on brain MRI in each dose group. |
| Change in EDSS Score in Each Dose Group [Safety of CLS12311] | Baseline to Week 48 (end of study) | Change from baseline to Week 48 in Expanded Disability Status Scale (EDSS) score in each dose group. The EDSS ranges from 0 to 10, with higher scores indicating greater disability. Negative values indicate improvement and positive values indicate worsening disability. |
| Change in T25-FW Performance in Each Dose Group [Safety of CLS12311] | Baseline to Week 48 (end of study) | Percent change from baseline to Week 48 in Timed 25-Foot Walk (T25-FW) performance in each dose group. Negative values indicate improvement (faster walking time). |
| Change in 9HPT Performance in Each Dose Group [Safety of CLS12311] | Baseline to Week 48 (end of study) | Percent change from baseline to Week 48 in 9-Hole Peg Test (9-HPT) performance in each dose group. Negative values indicate improvement (shorter completion time). |
| Change in SDMT Performance in Each Dose Group [Safety of CLS12311] | Baseline to Week 48 (end of study) | Change from baseline to Week 48 in Symbol Digit Modalities Test (SDMT) score. The SDMT is a cognitive processing speed test with scores ranging from 0 to approximately 110 points. Higher scores indicate better cognitive performance. |
Countries
Czechia, Germany, Italy, Switzerland
Participant flow
Recruitment details
Participants with relapsing-remitting multiple sclerosis were recruited at specialized clinical centers according to the protocol-defined inclusion and exclusion criteria between June 2024 and December 2025. A total of 11 participants underwent blood donation for CLS12311 manufacturing, of whom 9 received at least one treatment cycle.
Pre-assignment details
After enrollment, participants underwent blood donation for CLS12311 manufacturing and were assigned to the low-, medium-, or high-dose groups. Two participants discontinued after blood donation and did not receive treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 35.1 years STANDARD_DEVIATION 8.14 |
| Disease duration | 19.80 months STANDARD_DEVIATION 16.391 |
| EDSS score | 1.0 points STANDARD_DEVIATION 1.732 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 2 / 3 | 3 / 4 | 3 / 4 |
| serious Total, serious adverse events | 1 / 3 | 0 / 4 | 0 / 4 |
Outcome results
None listed