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

AstraZeneca

Status and phase: Begins enrollment in 1 month; Phase 1

Conditions: Multiple Sclerosis

Treatments: Biological: AZD0120 - Regimen 2; Biological: AZD0120 - Regimen 1

Study type: Interventional

Funder types: Industry

Identifiers

NCT07224373

29707 (Registry Identifier)

D831DC00001

Details and patient eligibility

About

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.

Full 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 evaulated per disease cohort.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 ≤ 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

18 participants in 2 patient groups

Arm/Group 1: AZD0120 RMS

Experimental group

Description:

AZD0120 RMS

Treatment:

Biological: AZD0120 - Regimen 1

Biological: AZD0120 - Regimen 2

Arm/Group 2: AZD0120 PMS

Experimental group

Description:

AZD0120 PMS

Treatment:

Biological: AZD0120 - Regimen 1

Biological: AZD0120 - Regimen 2