Multicenter Phase Ib/IIa Study on the Safety and Efficacy of Autologous Peptide-Coupled Red Blood Cells in Patients with Relapsing-Remitting Multiple Sclerosis

Czech Republic, Czechia, Germany, Italy, Switzerland (ICTRP)

ID di studio ICTRP
EUCTR2022-000801-28 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
Multicenter, Phase Ib/IIa Study on the Safety and Efficacy of Autologous Peptide-coupled Red Blood Cells in Patients with Relapsing Remitting Multiple Sclerosis (BASEC)

Titolo accademico
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 (ICTRP)

Titolo pubblico
Peptide-coupled Red Blood Cells for the Treatment of Multiple Sclerosis (ICTRP)

Malattie studiate
Relapsing Remitting Multiple Sclerosis (RRMS)
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)

Intervento studiato

Product Name: CLS12311
Product Code: [CLS12311]
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Eritrociti accoppiati a peptidi
Current Sponsor code: CLS12311
Other descriptive name: Peptide coupled red blood cells
Concentration unit: Other
Concentration type: range
Concentration number: 3-12
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use

Product Name: CLS12311
Product Code: [CLS12311]
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Eritrociti accoppiati a peptidi
Current Sponsor code: CLS12311
Other descriptive name: Peptide coupled red blood cells
Concentration unit: Other
Concentration type: range
Concentration number: 6-24
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Part A: open-label, ascending dose Part B: randomized, dose-blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

Inclusion criteria:
Part A and Part B
General inclusion criteria (to be assessed at the beginning of the screening period based on patient interview and medical history):
1. RRMS according to the 2017 McDonald criteria
2. Age 18-55 years
3. Disease duration (since diagnosis) <10 years
4. EDSS 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 mentioned under exclusion criterion No. 2
7. Only for sexually active female patients of childbearing potential (sexually mature, pre-menopausal and not surgically sterile): the patient is willing to use a medically accepted method of contraception (defined in the study protocol) from the first (V1) to the last study visit in Part A and up to V11 (week 24) in Part B
8. Male patients willing to use contraception (condoms) from the first to the last study visit in Part A and from the V3 (week 1) to the V11 (week 24) in Part B unless surgically sterile
9. 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

Part B
Specific qualification criteria (to be assessed during the baseline period):
10. = 2 cumulative new brain lesions (as defined above) on two MRI scans performed during baseline phase
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 142
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)

Exclusion criteria:
Part A and B
General exclusion criteria (to be assessed at the beginning of the screening period based on patient interview and medical history):
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 below within the specified time-frame (please refer to the section 8.1.2 of protocol)
3. History of HIV, chronic or active Hepatitis C, chronic or active Hepatitis B or prior Syphilis, which has not been sufficiently treated
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 ISH global practice guidelines) despite treatment or without treatment
9. History of stroke
10. Pregnant female confirmed by a positive pregnancy test or breastfeeding
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

Specific exclusion criteria (to be assessed during the screening period):
16. Anemia, defined as hemoglobin levels =125 g/dl (7.25 mmol/l) for female and =135 g/dl (8.37 mmol/l) for male participants (may be repeated if 115 -125 g/dl in females and 125 - 135 g/dl in males)
17. Erythrocyte count <4.0 G/l in female and <4.5 G/l in male patients (may be repeated if >3.8 G/l in female and >4.3 G/l in male)
18. Lymphopenia with total lymphocyte counts = 1000/?l (may be repeated if >800/?l)
19. Positive HIV testing
20. Positive results of screening 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 regulation
22. Having one or more of the following laboratory results (please refer to the section 8.1.2 of protocol)


Endpoint primari e secondari
Main Objective: Safety objective (Part A and B)
To assess the safety and tolerability of CLS12311 in patients with RRMS

Efficacy objective (Part B)
To provide proof-of-concept for the efficacy of CLS12311 in reducing the number of new lesions on brain magnetic resonance imaging (MRI) as a measure for inflammatory disease activity in patients with RRMS;Secondary Objective: Safety objectives (Part A and B)
To assess the safety and tolerability of each dose group of CLS12311

Efficacy objective (Part B)
To define the optimal dose of CLS12311 to reduce new disease activity on brain MRI in RRMS patients

Exploratory objective (Part A and B)
To understand the mechanism/s of action of tolerance induction with peptide-coupled RBCs and to identify biomarkers for measuring immune tolerance induction;Primary end point(s): Safety (Part A and B)
? 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 brain lesions)

Efficacy (Part B only)
? The cumulative number of new brain lesions on the MRI scans developed in the post-treatment phase between weeks 16 and 24 compared to the pre-treatment number of new brain MRI lesions developed between weeks -8 and 0 for any dose.

New lesions on brain MRI are defined as being:
? Contrast enhancing lesions on the reference scan at weeks -8 and 16
or
? new/enlarging T2 lesions on scan at:
? week 0 compared to scan at week -8
? week 24 compared to scan at week 16

MRIs will be assessed centrally by independent readers.;Timepoint(s) of evaluation of this end point: At the end of the trial (ICTRP)

Secondary end point(s): Safety endpoints (Part A and B):
? Number and severity of TEAEs and TESAEs in each dose group
? Number of confirmed relapses in the treatment phase in each dose group
? Changes in clinical measures of disease severity (EDSS, 9-HPT, T25FWT, SDMT) following CLS12311 administration in each dose group (Part A only EDSS)

Efficacy endpoints (Part B):
? Number of new lesions on brain MRI (as defined above) in weeks 16-24 in the three dose groups
? Efficacy of CLS12311 in reducing the number of new brain MRI lesions (as defined above) in defined subgroups, e.g. stratified for HLA or immunological parameters

Exploratory immunological and biomarker measures (Part A and B):
? Percentage of patients in each dose group showing a reduction of antigen-specific T cells against the protein(s) they responded to at study entry
? Changes in predefined serum biomarkers of disease activity and in other markers related to tolerance induction

Mechanistic profiling of serum and blood cells will be performed by measuring specific biomarkers of tolerance, tissue damage and inflammation as well as broad-based methods including but not limited to multi-analyte measurements, transcriptomics and proteomics.;Timepoint(s) of evaluation of this end point: At the end of the trial (ICTRP)

Data di registrazione
15.03.2023 (ICTRP)

Inclusione del primo partecipante
08.11.2023 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Administrative Office, info@cellerys.com, +41415449880, Cellerys AG (ICTRP)

ID secondari
MSB-IG-H-2101, 2022-000801-28-DE (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2022-000801-28 (ICTRP)