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

Relapsing-remitting Multiple Sclerosis (RRMS) Clinical Trial

— RED4MS  

Official title:

Multicenter, Phase Ib/IIa Study on the Safety and Efficacy of Autologous Peptide-coupled Red Blood Cells in Patients With Relapsing Remitting Multiple Sclerosis - RED4MS Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06430671
• Other study ID #: MSB-IG-H-2101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 18, 2024
• Est. completion date: March 2027

Study information

• Verified date: June 2024
• Source: Cellerys AG
• Contact: Andreas Lutterotti, MD
• Phone: +41 41 544 98 80
• Email: alutterotti[@]cellerys.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: March 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-remitting Multiple Sclerosis (RRMS)
• Sclerosis

Intervention

Drug:
• CLS12311 low
Peptide-coupled Red Blood Cells (RBCs)
• CLS12311 medium
Peptide-coupled Red Blood Cells (RBCs)
• CLS12311 high
Peptide-coupled Red Blood Cells (RBCs)
• uncoupled RBCs
autologous Red Blood Cells (RBCs)

Locations

Country	Name	City	State
Czechia	RS Centrum - Neurologická klinika	Praha
Czechia	Neurologická klinika 2. LF UK a FN Motol	Praha 5
Germany	Universitätsklinikum Carl Gustav Carus, Klinik für Neurologie	Dresden	Sachsen
Germany	Fraunhofer Institut fürTranslationale Medizin und Pharmakologie (ITMP)	Göttingen	Niedersachsen
Germany	Universitätsklinikum Hamburg-Eppendorf (UKE), Klinik für Neurologie	Hamburg
Germany	Universitätsklinikum Mannheim, Klinik für Neurologie	Mannheim	Baden-Württemberg
Germany	Klinikum rechts der Isar Technische Universität München, Klinik für Neurologie	München	Bayern
Germany	Universitätsklinikum Münster (UKM), Klinik für Neurologie	Münster	Nordrhein-Westfalen
Germany	Universitätsklinikum Ulm, Klinik für Neurologie	Ulm
Switzerland	Bellevue Medical Group (BMG), Neurozentrum	Zürich
Switzerland	UniversitätsSpital Zürich (USZ), Klinik für Neurologie	Zürich

Sponsors (5)

Lead Sponsor	Collaborator
Cellerys AG	Jung Diagnostics GmbH, Novartis, Scope International AG, Tetec AG

Countries where clinical trial is conducted

Czechia,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-related adverse events as assessed by CTCAE v4.0 and worsening of MS [Safety of CLS12311]	Number and severity of adverse events (AEs) and serious adverse events (SAEs) and worsening of disease measured by clinical (relapses) and imaging (number & size of brain MRI lesions)	on average 48 weeks
Primary	Overall reduction in the number of new brain lesions in treatment phase vs. pre-treatment phase [Efficacy of CLS12311]	The cumulative number of new brain lesions on the MRI scans developed in the post-treatment phase during weeks 16-24 compared to pre-treatment number of new brain lesions developed during weeks -8 and 0 for any dose	completion of treatment phase, on average 24 weeks
Secondary	Incidence of treatment-related adverse events as assessed by CTCAE v4.0 in each dose group [Safety of CLS12311]	Number and severity of treatment-emergent AEs (TEAEs) and treatment-emergent SAEs (TESAEs) in each dose group	on average 48 weeks
Secondary	Incidence of patients experiencing worsening of MS in each dose group [Safety of CLS12311]	Number of confirmed relapses in the treatment phase in each dose group	on average 48 weeks
Secondary	Incidence of patients experiencing worsening of EDSS in each dose group [Safety of CLS12311]	Change in Expanded Disability Status Scale (EDSS) in each dose group	on average 48 weeks
Secondary	Incidence of patients experiencing worsening of T25-FW in each dose group [Safety of CLS12311]	Change in Timed 25-Foot Walk (T25-FW) in each dose group	on average 48 weeks
Secondary	Incidence of patients experiencing worsening of 9-HPT in each dose group [Safety of CLS12311]	Change in 9-Hole Peg Test (9-HPT) in each dose group	on average 48 weeks
Secondary	Incidence of patients experiencing worsening of SDMT in each dose group [Safety of CLS12311]	Change in Symbol Digit Modalities Test (SDMT) in each dose group	on average 48 weeks
Secondary	Efficacy of CLS12311 in reducing number of new brain lesions as a surogate for inflammatory disease activity	Number of new lesions on brain MRI in weeks 16-24 in each dose group	completion of treatment phase, on average 24 weeks
Secondary	Efficacy of CLS12311 in reducing the number of new brain lesions in defined subgroups	Number of new brain lesions in defined subgroups, stratified for HLA or immunological parameters through the treatment phase	completion of treatment phase, on average 24 weeks