Multicenter Phase Ib/IIa Study on the Safety and Efficacy of Autologous Peptide-Coupled Red Blood Cells in Patients with Relapsing-Remitting Multiple Sclerosis
Zusammenfassung der Studie
Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS = brain and spinal cord). As a result of the inflammation, demyelination occurs in the nerve pathways, which in turn, depending on the location of the inflammation, triggers the corresponding disease symptoms. It is believed that the damage in the CNS is caused by an immune system reaction against the body's own tissue (=autoimmune). Although there have been significant advances in the treatment of MS over the last 20 years, there remains an unmet medical need for therapies that specifically target the pathogenic immune response. This study aims to investigate the efficacy and safety of peptide-coupled red blood cells (CLS12311) in patients with RRMS. The treatment goal is to stop the inflammation in the brain and prevent the occurrence of new symptoms, known as relapses. This is a two-part study consisting of Part A (Phase Ib study) and Part B (Phase IIa study). With this clinical study, we aim to investigate in Part A, where the dose is continuously increased (so-called dose escalation), as well as in Part B, where three dosages of CLS12311 are tested (so-called blinded treatment), how well tolerated CLS12311 is and whether efficacy effects can be measured. A total of 54 patients will be treated at approximately 20 study centers in various European countries.
(BASEC)
Untersuchte Intervention
Part A of the study: A total of 9 patients will be treated in three different dosage groups. Patients will be assigned to the low (n=2), medium (n=3), or high (n=4) dosage group according to the order of recruitment. Each dosage group starts with a sentinel patient (n=3) who receives only one treatment cycle in weeks 2 and 3, i.e., a total of 3x10^11, 6x10^11, or 12x10^11 of CLS12311. The remaining patients (n=6) will receive two treatment cycles with the corresponding dosage in weeks 2 and 3 and then 12 and 13, i.e., a total of 6x10^11, 12x10^11, or 24x10^11 of CLS12311. A transition from the first to the second treatment cycle or an increase in dosage to the next higher group is only recommended when the medical experts of the sponsor have confirmed safety based on (S)AEs and relapses at week 4 or week 7. All patients qualifying for Part A of the study will be observed for at least 48 weeks, of which 17 weeks in the treatment phase and 31 weeks in the safety observation. Part B of the study will involve 45 patients. After an 8-week pre-examination phase, patients will be randomly assigned to one of three treatment groups: 1: CLS12311 low dose (6x10^11), 2: CLS12311 medium dose (12x10^11), 3: CLS12311 high dose (24x10^11). Each patient will receive two cycles of study treatment... All patients qualifying for participation in Part B of the study will be monitored for at least 48 weeks, of which 24 weeks in the treatment phase and 24 weeks in the safety observation. In both parts of the study, a treatment cycle consists of two infusions within one week (a total of 4 infusion bags, each 150 ml). Patients will be asked to donate approximately 450-500 ml of blood for the production of the therapy, which will be processed into peptide-coupled red blood cells (CLS12311) or placebo. The following examinations may be performed once or multiple times during the study: physical and neurological examination, blood and urine tests, magnetic resonance imaging (MRI), electrocardiogram (ECG), assessment of the severity of MS-related disability, as well as attention and concentration.
(BASEC)
Untersuchte Krankheit(en)
Relapsing-Remitting Multiple Sclerosis
(BASEC)
- RRMS according to the McDonald criteria 2017 - Duration of disease (since diagnosis) < 10 years - Untreated patients or patients who have not been treated since the periods mentioned in exclusion criterion no. 2 (BASEC)
Ausschlusskriterien
- Previous treatment with any of the medications listed below within the specified time frame: a. Glatiramer acetate, Interferon-beta within 4 weeks prior to screening visit 1 b. Dimethyl fumarate, Diroximel fumarate within 4 weeks prior to screening visit 1 c. Teriflunomide within 4 weeks prior to screening visit 1, provided that an accelerated elimination procedure (e.g., cholestyramine) has been performed, and the teriflunomide plasma concentration is less than 0.02 mg/l prior to randomization d. Fingolimod, Ozanimod within 12 weeks prior to screening visit 1, provided that lymphocyte counts are normal (see exclusion criterion no. 18) e. Siponimod, Ponesimod within 8 weeks prior to screening visit 1, provided that lymphocyte counts are normal (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 therapy with immunosuppressants within 24 weeks prior to screening visit 1 j. any other treatment with immunosuppressive monoclonal antibodies within 24 weeks prior to screening visit 1 k. Previous autologous hematopoietic stem cell transplantation l. Treatment with corticosteroids for MS relapses within 4 weeks prior to screening visit 1 m. Patients who have participated in the ETIMSred study - Pregnant women whose pregnancy has been confirmed by a positive pregnancy test, or breastfeeding women - Relevant central nervous system disease (other than MS) in the medical history or currently predominant (BASEC)
Studienstandort
Bern, Zürich
(BASEC)
Sponsor
not applicable
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Dr. Nikolai Pfender
+41 (0)44 295 30 49
nikolai.pfender@clutterbmg-swiss.chBellevue Medical Group, Neurozentrum Bellevue
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
27.01.2023
(BASEC)
ICTRP Studien-ID
CTIS2023-510127-30-00 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
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)
Wissenschaftlicher Titel
Multicenter, Phase Ib/IIa Study on the Safety and Efficacy of Autologous Peptide-coupled Red Blood Cells in Patients with Relapsing Remitting Multiple Sclerosis - MSB-IG-H-2101 (ICTRP)
Öffentlicher Titel
Peptide-coupled Red Blood Cells for the Treatment of Multiple Sclerosis (ICTRP)
Untersuchte Krankheit(en)
Relapsing Remitting Multiple Sclerosis (RRMS)
MedDRA version: 21.1Level: PTClassification code: 10063399Term: Relapsing-remitting multiple sclerosis Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)
Untersuchte Intervention
Product Name: Autologous uncoupled red blood cells (RBCs), Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A , Product Name: , Product Code:PRD10364988, Pharmaceutical Form: DISPERSION FOR INFUSION, Other descriptive name: , Strength: (ICTRP)
Studientyp
Interventional clinical trial of medicinal product (ICTRP)
Studiendesign
Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Number of treatment arms in the trial: 3 (ICTRP)
Ein-/Ausschlusskriterien
Inclusion criteria: [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, [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, [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, [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, [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, [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, [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, [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 (ICTRP)
Exclusion criteria: [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), [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, [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, [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, [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), [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, [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, [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), [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), [Specific exclusion criteria (to be assessed during the baseline period)]: Lymphopenia with total lymphocyte counts = 1000/l (may be repeated if >800/l), [Specific exclusion criteria (to be assessed during the baseline period)]: Positive HIV testing, [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. ocr
Primäre und sekundäre Endpunkte
Main Objective: Safety objective: To assess the safety and tolerability of CLS12311 in patients with RRMS;Secondary Objective: Safety objectives: To assess the safety and tolerability of each dose group of CLS12311, 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;Primary end point(s): 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. (ICTRP)
Secondary end point(s):[Safety endpoints]: Number and severity of TEAEs and TESAEs in each dose group;Secondary end point(s):[Safety endpoints]: Number of confirmed relapses in the treatment phase in each dose group;Secondary end point(s):[Safety endpoints]: Changes in clinical measures of disease severity (EDSS, 9-HPT, T25- FW, SDMT) following CLS12311 administration in each dose group;Secondary end point(s):[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;Secondary end point(s):[Exploratory immunological and biomarker measures]: Changes in predefined serum- and cellular biomarkers including autoantigen-specific T cell responses that would indicate proinflammatory activation (ICTRP)
Registrierungsdatum
26.08.2024 (ICTRP)
Einschluss des ersten Teilnehmers
18.06.2024 (ICTRP)
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Administrative Office, info@cellerys.com, +41415449880, Cellerys AG (ICTRP)
Sekundäre IDs
NCT06430671, 2022-000801-28, NCT06430671 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
No (ICTRP)
Weitere Informationen zur Studie
https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-510127-30-00 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar