## Protocol Section
### Identification Module
**NCT ID:** NCT06430671

**Acronym:** RED4MS

**Brief Title:** Peptide-coupled Red Blood Cells for the Treatment of Multiple Sclerosis

**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

#### Organization Study ID Info
**ID:** MSB-IG-H-2101
#### Organization
**Class:** INDUSTRY
**Full Name:** Cellerys AG
### Status Module
#### Completion Date
**Date:** 2027-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-08

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-06
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Novartis

**Class:** INDUSTRY

**Name:** Scope International AG

**Class:** INDUSTRY

**Name:** Tetec AG

**Class:** INDUSTRY

**Name:** Jung Diagnostics GmbH

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Cellerys AG

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief 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.

**Detailed 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.

### Conditions Module

**Conditions:**

- Relapsing-remitting Multiple Sclerosis (RRMS)

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Individual patients will be assigned to three parallel dose groups. In Part A patients will be allocated in the low, medium, high dose group according to the order of recruitment. In Part B patients will be randomized in a ratio 1:1:1 into one of the three dosing groups.

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** Part A is an open label Phase I trial Part B is randomized, dose-blinded Phase II trial

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 135

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Low dose CLS12311

**Intervention Names:**

- Drug: CLS12311 low

- Drug: uncoupled RBCs

**Label:** CLS12311 low

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Medium dose CLS12311

**Intervention Names:**

- Drug: CLS12311 medium

- Drug: uncoupled RBCs

**Label:** CLS12311 medium

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** High dose CLS12311

**Intervention Names:**

- Drug: CLS12311 high

**Label:** CLS12311 high

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- CLS12311 low

**Description:** Peptide-coupled Red Blood Cells (RBCs)

**Name:** CLS12311 low

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- CLS12311 medium

**Description:** Peptide-coupled Red Blood Cells (RBCs)

**Name:** CLS12311 medium

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- CLS12311 high

**Description:** Peptide-coupled Red Blood Cells (RBCs)

**Name:** CLS12311 high

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- CLS12311 low

- CLS12311 medium

**Description:** autologous Red Blood Cells (RBCs)

**Name:** uncoupled RBCs

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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)

**Measure:** Incidence of treatment-related adverse events as assessed by CTCAE v4.0 and worsening of MS [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** 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

**Measure:** Overall reduction in the number of new brain lesions in treatment phase vs. pre-treatment phase [Efficacy of CLS12311]

**Time Frame:** completion of treatment phase, on average 24 weeks

#### Secondary Outcomes

**Description:** Number and severity of treatment-emergent AEs (TEAEs) and treatment-emergent SAEs (TESAEs) in each dose group

**Measure:** Incidence of treatment-related adverse events as assessed by CTCAE v4.0 in each dose group [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** Number of confirmed relapses in the treatment phase in each dose group

**Measure:** Incidence of patients experiencing worsening of MS in each dose group [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** Change in Expanded Disability Status Scale (EDSS) in each dose group

**Measure:** Incidence of patients experiencing worsening of EDSS in each dose group [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** Change in Timed 25-Foot Walk (T25-FW) in each dose group

**Measure:** Incidence of patients experiencing worsening of T25-FW in each dose group [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** Change in 9-Hole Peg Test (9-HPT) in each dose group

**Measure:** Incidence of patients experiencing worsening of 9-HPT in each dose group [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** Change in Symbol Digit Modalities Test (SDMT) in each dose group

**Measure:** Incidence of patients experiencing worsening of SDMT in each dose group [Safety of CLS12311]

**Time Frame:** on average 48 weeks

**Description:** Number of new lesions on brain MRI in weeks 16-24 in each dose group

**Measure:** Efficacy of CLS12311 in reducing number of new brain lesions as a surogate for inflammatory disease activity

**Time Frame:** completion of treatment phase, on average 24 weeks

**Description:** Number of new brain lesions in defined subgroups, stratified for HLA or immunological parameters through the treatment phase

**Measure:** Efficacy of CLS12311 in reducing the number of new brain lesions in defined subgroups

**Time Frame:** completion of treatment phase, on average 24 weeks

### Eligibility Module

**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

**Maximum Age:** 55 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** alutterotti@cellerys.com

**Name:** Andreas Lutterotti, MD

**Phone:** +41 41 544 98 80

**Role:** CONTACT

**Contact 2:**

**Email:** nfournichot@cellerys.com

**Name:** Nathalie Fournichot

**Phone:** +41 41 544 98 80

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020278

- Term: Demyelinating Autoimmune Diseases, CNS

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000003711

- Term: Demyelinating Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC20

- Name: Immune System Diseases

### Condition Browse Module - Browse Leaves

- ID: M15415

- Name: Sclerosis

- Relevance: HIGH

- As Found: Sclerosis

- ID: M12060

- Name: Multiple Sclerosis

- Relevance: HIGH

- As Found: Multiple Sclerosis

- ID: M22314

- Name: Multiple Sclerosis, Relapsing-Remitting

- Relevance: HIGH

- As Found: Relapsing Remitting Multiple Sclerosis

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22098

- Name: Demyelinating Autoimmune Diseases, CNS

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M6909

- Name: Demyelinating Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009103

- Term: Multiple Sclerosis

- ID: D000020529

- Term: Multiple Sclerosis, Relapsing-Remitting

- ID: D000012598

- Term: Sclerosis

### Misc Info Module

- Version Holder: 2024-05-31
