Multiple Sclerosis
Conditions
Keywords
AZD0120, Multiple Sclerosis, MS, RMS, PMS
Brief summary
This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with Multiple Sclerosis.
Detailed description
This study will evaluate AZD0120 for safety, including DLTs and TEAEs, by the SRC for determination of the Recommended Phase 2 dose for each disease cohort. Approximately 9-12 participants will be evaluated per disease cohort.
Interventions
BIOLOGICALAZD0120 - Regimen 1
Regimen 1, infusion of AZD0120
BIOLOGICALAZD0120 - Regimen 2
Regimen 2, infusion of AZD0120
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Age ≥ 18-years-old to ≤ 60-years-old at the time of consent Type of Participant and Disease Characteristics 2. Written informed consent in accordance with federal, local, and institutional guidelines 3. Adequate physiological function and reserve at screening RMS Cohort Specific Inclusion Criteria 4. Diagnosis of RMS according to the 2024 McDonald Criteria (Montalban et al 2025) or diagnosis of relapsing, active SPMS according to Lublin et al 2014. 5. Participants should have an EDSS of ≤ 6.5 at screening. 6. Evidence of active disease (clinical relapses and MRI activities within 2 years prior to screening), or intolerance, while on a high efficacy disease-modifying therapy for ≥ 6 months. PMS Cohort Specific Inclusion Criteria 7. Diagnosis of PPMS according to the 2024 McDonald Criteria (Montalban et al 2025) or non-relapsing SPMS according to Lublin et al 2014. 8. Participants must have an EDSS of ≥ 3.0 and ≤ 6.5 at screening. 9. Inadequate response ≥ 1 heDMT with ≥ 6 months treatment or intolerance.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: 1. Any prior CAR-T or CAR-NK cell exposure. 2. Underwent splenectomy within 12 months prior to signing the ICF. 3. Received a solid organ transplant at any time or on an active transplant waiting list. 4. Prior treatment with autologous hematopoietic stem cell transplantation or total lymphoid irradiation. 5. Cardiac conditions or any other significant cardiac condition that would present undue risk to the participant in the investigator's opinion: 6. Any other central nervous system disease including epilepsy, convulsive seizures, organic encephalopathy syndrome, non-MS related paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease or associated movement disorder, psychosis, CNS vasculitis, or any other neurological disease that may impact the ability to evaluate neurotoxicity. History of a seizure disorder even if the seizure disorder is well controlled with anti-epileptics. 7. Participant has significant psychiatric condition (active or history of). 8. History of other immune-mediated disease that required continued systemic immunosuppression/systemic disease-modifying agents. 9. Evidence of clinically significant bleeding or active bleeding diathesis within 90 days before screening 10. History of malignancy or ongoing treatment for prior malignancy. 11. Inborn error of immunity and/or primary immunodeficiency. 12. Seropositive for HIV or HTLV (including any history of HIV or HTLV). 13. Active viral (any etiology, HBV, HCV) hepatitis are excluded. 14. Major surgery within 4 weeks prior to apheresis or lymphodepletion or has surgery planned during the study or within 4 weeks after study treatment administration. 15. Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment, whichever is longer. 16. Unwilling or unsafe to proceed with CSF exams based on coagulopathy or anatomy or other considerations in the judgment of the study investigator. 17. Any contraindications to LP. 18. Participants not willing, able, or are unsafe to take MRI scans as per protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS) | Day 1 to day 29, and over 104 weeks | Incidence and severity of Dose Limiting Toxicity (DLT) over 104 weeks following AZD0120 administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the optimum regimen with AZD0120 in MS participants to determine the RP2D in each disease cohort | Over 104 weeks | Change from baseline in peripheral B-cell counts following AZD0120 administration |
| Evaluate the preliminary efficacy of AZD0120 in RMS and PMS | Over 104 weeks | Annualized Relapse Rate (ARR) over 104 weeks (RMS cohort only) |
| Investigate the effects of AZD0120 on the function and quality of life of participants with MS | Over 104 weeks | Change in SF-36v2 from baseline |
| Characterize the CK and PD of AZD0120 in participants with MS | Over 104 weeks | Quantification of CAR transgene levels of AZD0120 in blood and CSF. |
| To monitor the incidence of vector-derived RCL | Over 104 weeks | Proportion of participants with detectable RCL at pre-specified post infusion timepoints |
| To assess the immunogenicity of AZD0120 in participants. | over 104 weeks | Proportion of participants who develop anti- AZD0120 antibodies |
Countries
Australia, Canada, Germany, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed