An Open-label Study of AZD0120 in Adults With Multiple Sclerosis

Phase 1RecruitingNCT07224373

AstraZeneca24 enrolled

Overview

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.

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 evaulated per disease cohort.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Sclerosis

Interventions

AZD0120 - Regimen 1BIOLOGICAL

Regimen 1, infusion of AZD0120

AZD0120 - Regimen 2BIOLOGICAL

Regimen 2, infusion of AZD0120

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Age ≥ 18-years-old to ≤ 75-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 2017 McDonald Criteria (Thompson et al 2018) 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 2017 McDonald Criteria (Thompson et al 2018) and/or diagnosis of not active progressive 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. 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.

Locations (13)

Research Site

Tucson, Arizona, United States

NOT_YET_RECRUITING

Research Site

Aurora, Colorado, United States

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS)

Incidence and severity of Dose Limiting Toxicity (DLT) over 104 weeks following AZD0120 administration.

Time frame: Day 1 to day 29, and over 104 weeks

Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS)

Incidence and severity of Adverse Events (AE) over 104 weeks following AZD0120 administration.

Time frame: Day 1 to day 29, and over 104 weeks

Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS)

Incidence and severity of Serious Adverse Events (SAE) over 104 weeks following AZD0120 administration.

Time frame: Day 1 to day 29, and over 104 weeks

Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS)

Incidence and severity of Treatment Emergent Adverse Events (TEAE) over 104 weeks following AZD0120 administration.

Time frame: Day 1 to day 29, and over 104 weeks

Secondary Outcomes

Evaluate the optimum regimen with AZD0120 in MS participants to determine the RP2D in each disease cohort

Change from baseline in peripheral B-cell counts following AZD0120 administration

Time frame: Over 104 weeks

Evaluate the optimum regimen with AZD0120 in MS participants to determine the RP2D in each disease cohort

CK parameters in peripheral B-cell counts following AZD0120 administration

Time frame: Over 104 weeks

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Washington D.C., District of Columbia, United States

NOT_YET_RECRUITING

Research Site

St Louis, Missouri, United States

RECRUITING

Research Site

New York, New York, United States

NOT_YET_RECRUITING

Research Site

New York, New York, United States

RECRUITING

Research Site

Cleveland, Ohio, United States

NOT_YET_RECRUITING

Research Site

Seattle, Washington, United States

NOT_YET_RECRUITING

Research Site

Milwaukee, Wisconsin, United States

NOT_YET_RECRUITING

Research Site

Liverpool, Australia

NOT_YET_RECRUITING

...and 3 more locations