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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cellerys AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 Apr 2024 → 24 Dec 2025

Decision date (initial)

2024-09-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis

External identifiers

EU CT number

2023-510127-30-00

EudraCT number

2022-000801-28

ClinicalTrials.gov

NCT06430671

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Safety objective: To assess the safety and tolerability of CLS12311 in patients with RRMS

Secondary objectives 2

1. Safety objectives: To assess the safety and tolerability of each dose group of CLS12311
2. Exploratory objective: To understand the mechanism/s of action of tolerance induction with peptide-coupled RBCs and to identify biomarkers for measuring immune tolerance induction

Conditions and MedDRA coding

Relapsing Remitting Multiple Sclerosis (RRMS)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. [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
2. [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
3. [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
4. [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
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
6. [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
7. [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
8. [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 22

1. [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)
2. [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
3. [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
4. [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Long-COVID19 Syndrome
5. [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
6. [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
7. [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: Current anticoagulation therapy
8. [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
9. [General exclusion criteria (to be assessed at the beginning of the baseline period based on patient interview and medical history)]: History of stroke
10. [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
11. [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
12. [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
13. [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)
14. [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
15. [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
16. [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)
17. [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)
18. [Specific exclusion criteria (to be assessed during the baseline period)]: Lymphopenia with total lymphocyte counts ≤ 1000/µl (may be repeated if >800/µl)
19. [Specific exclusion criteria (to be assessed during the baseline period)]: Positive HIV testing
20. [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
21. [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
22. [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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety endpoint: Safety and tolerability of CLS12311 measured by the number and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) and/or worsening of disease by clinical (relapses) and imaging (number and size of MRI brain lesions). MRIs will be assessed centrally by independent readers.

Secondary endpoints 5

1. [Safety endpoints]: Number and severity of TEAEs and TESAEs in each dose group
2. [Safety endpoints]: Number of confirmed relapses in the treatment phase in each dose group
3. [Safety endpoints]: Changes in clinical measures of disease severity (EDSS, 9-HPT, T25- FW, SDMT) following CLS12311 administration in each dose group
4. [Exploratory immunological and biomarker measures]: Percentage of patients in each dose group showing a reduction of antigen-specific T cells against the protein(s) they responded to at the study entry
5. [Exploratory immunological and biomarker measures]: Changes in predefined serum- and cellular biomarkers including autoantigen-specific T cell responses that would indicate proinflammatory activation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cellerys AG

Sponsor organisation

Cellerys AG

Address

Wagistrasse 21

City

Schlieren

Postcode

8952

Country

Switzerland

Scientific contact point

Organisation

Cellerys AG

Contact name

Administrative Office

Public contact point

Organisation

Cellerys AG

Contact name

Administrative Office

Third parties 42

Locations

3 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications