Peptide-coupled Red Blood Cells for the Treatment of Multiple Sclerosis

RED4MS is a clinical trial to assess the safety, tolerability and efficacy of autologous peptide coupled red blood cells (CLS12311) in patients with relapsing remitting multiple sclerosis (RRMS). CLS12311 consists of autologous red blood cells (RBCs) chemically coupled with antigenic peptides and aims to treat RRMS by induction of antigen-specific immune tolerance.

The RED4MS trial is designed as a combination of a phase Ib (part A) and a phase IIa (part B) study.

Part A is an open-label, dose-escalation 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.

Part B is a baseline-to-treatment, dose-blinded, randomized study and is designed to test the safety and efficacy of three different doses of CLS12311. During baseline phase, a total of 45 patients with active disease on magnetic resonance imaging (MRI) will be selected for the treatment phase and randomized in a 1:1:1 ratio into one of three dosing groups. Each patient will receive two cycles of therapy.

Eligibility Criteria:
Inclusion Criteria (Part A and B):

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. ≥1 relapse or new CEL/T2 in previous 12 months (only Part B)
6. 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
7. 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
8. 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 (Part A and B):

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