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

A Phase 1b, Open-label, Multi-center, Randomized Study Evaluating the Safety and Tolerability of AZD0120, an Autologous CD19/BCMA Targeting Chimeric Antigen Receptor T-cells, in Adults With Refractory Relapsing or Progressive Multiple Sclerosis

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: AZD0120 - Regimen 1; Biological: AZD0120 - Regimen 2

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Liverpool, Australia, 2170
    • Not yet recruiting
    • Research Site
  • Melbourne, Australia, 3000
    • Recruiting
    • Research Site
  • Melbourne, Australia, 3004
    • Not yet recruiting
    • Research Site
  • Waratah, Australia, 2298
    • Not yet recruiting
    • Research Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Not yet recruiting
      • Research Site
• Germany
  • Leipzig, Germany, 04103
    • Withdrawn
    • Research Site
  • Magdeburg, Germany, 39120
    • Withdrawn
    • Research Site
  • Würzburg, Germany, DE-97072
    • Withdrawn
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • Withdrawn
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Withdrawn
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Withdrawn
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • Research Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Not yet recruiting
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Research Site
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Research Site
    • New York, New York, United States, 10016
      • Recruiting
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Recruiting
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm/Group 1: AZD0120 RMS; AZD0120 RMS	Biological: AZD0120 - Regimen 1; Regimen 1, infusion of AZD0120; Biological: AZD0120 - Regimen 2; Regimen 2, infusion of AZD0120
Experimental: Arm/Group 2: AZD0120 PMS; AZD0120 PMS	Biological: AZD0120 - Regimen 1; Regimen 1, infusion of AZD0120; Biological: AZD0120 - Regimen 2; Regimen 2, infusion of AZD0120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Day 1 to day 29, and over 104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Annualized Relapse Rate (ARR) over 104 weeks (RMS cohort only)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Time to onset participants with CDP-12 over 104 weeks	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Proportion of participants with CDP-12 over 104 weeks	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Time to onset participants with CDP-24 over 104 weeks	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Proportion of participants with CDP-24 over 104 weeks	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Proportion of participants achieving CDI	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from baseline in 9HPT (9-Hole Peg Test)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from baseline in T25FW (Timed 25-Foot Walk)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from baseline in EDSS (Expanded Disability Status Scale)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from baseline in SDMT (Symbol Digit Modalities Test)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Proportion of participants with NEDA-3 (No Evidence of Disease Activity)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Proportion of participants with PIRA (Progression Independent of Relapse Activity)	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from screening in MRI parameters including: mean number of Gd+ T1 lesions over time	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from screening in MRI parameters including: mean number of new or enlarging T2 hyperintense lesions	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change from screening in MRI parameters including brain volume	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change in MRI parameters including: mean number of Gd+ T1 lesions over time.	Over 104 weeks
Evaluate the preliminary efficacy of AZD0120 in RMS and PMS	Change in MRI parameters including: mean number of new or enlarging T2 hyperintense lesions	Over 104 weeks
Investigate the effects of AZD0120 on the function and quality of life of participants with MS	Change in SF-36v2 from baseline	Over 104 weeks
Investigate the effects of AZD0120 on the function and quality of life of participants with MS	Change in Neuro-QoL-fatigue from baseline	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	Quantification of CAR transgene levels of AZD0120 in blood and CSF.	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	Cmax	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	AUC(0-28).	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	AUClast.	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	Clast.	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	Tmax.	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	Tlast.	Over 104 weeks
Characterize the CK and PD of AZD0120 in participants with MS	B-cell counts	Over 104 weeks
To monitor the incidence of vector-derived RCL	Proportion of participants with detectable RCL at pre-specified post infusion timepoints	Over 104 weeks
To assess the immunogenicity of AZD0120 in participants.	Proportion of participants who develop anti- AZD0120 antibodies	over 104 weeks
To assess the immunogenicity of AZD0120 in participants.	Time to development of anti-AZD0120 antibodies	over 104 weeks
To assess the immunogenicity of AZD0120 in participants.	Changes in anti-AZD0120 antibody titers over 104 weeks	over 104 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2025
• Primary Completion (Estimated): December 7, 2028
• Study Completion (Estimated): December 7, 2028

Study Registration Dates

• First Submitted: October 21, 2025
• First Submitted That Met QC Criteria: October 31, 2025
• First Posted (Actual): November 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; MS; PMS; RMS; AZD0120
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis
• Other Study ID Numbers: D831DC00001; 29707 (Other Identifier: IND)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No