FT819 in Moderate to Severe Active Systemic Lupus Erythematosus

A Phase 1 Study of FT819 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus

This is a phase 1 study designed to evaluate the safety, pharmacokinetics (PK), and anti-B-cell activity of FT819 following conditioning chemotherapy in participants with moderate to severe active systemic lupus erythematosus (SLE). The study will consist of a dose-escalation stage, followed by an expansion stage to further evaluate the safety and activity of FT819.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Bendamustine; Drug: FT819

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fate Trial Disclosure; Phone Number: 866-875-1800; Email: FateTrialDisclosure@fatetherapeutics.com

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Medical School
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female adults ≥18 years and <40 years of age at the time of signing the informed consent form (ICF).
• Diagnosed with SLE by the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria.
• Positivity for antinuclear antibody, anti-ds-DNA antibody, and/or anti-Smith antibody at screening.
• Active SLE at screening, as defined by SLEDAI ≥8 points (with a clinical SLEDAI ≥4 points, excluding alopecia, mucosal ulcers, and fever); AND one or more major organ systems with British Isles Lupus Assessment Group (BILAG) A score, excluding musculoskeletal, mucocutaneous, and/or constitutional organ systems.
• Failure to respond to glucocorticoids and ≥2 of the following treatments for at least 3 months: cyclophosphamide (CY), mycophenolic acid or its derivatives, belimumab, methotrexate, azathioprine, anifrolumab, rituximab, obinutuzumab, cyclosporin, tacrolimus, or voclosporin.

Exclusion Criteria:

• Active neurological symptoms of SLE at screening.
• Potentially irreversible organ damage related to SLE, where in the opinion of the investigator, CD19 CAR T-cell therapy would be unlikely to benefit the participant.
• Non-malignant CNS disease such as stroke, epilepsy, or neurodegenerative disease or receipt of medications for these conditions within 2 years prior to study enrollment.
• Prior treatment with CAR T-cell therapy, allograft organ transplant, or hematopoietic stem cell transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FT819; Participants with moderate to severe active SLE.

Drug: Fludarabine; Fludarabine will be administered as an IV infusion at planned dose levels.; Other Names: FLUDARA; Drug: Cyclophosphamide; Cyclophosphamide will be administered as an IV infusion at planned dose levels.; Other Names: CYTOXAN; Drug: Bendamustine; Bendamustine will be administered as an IV infusion at planned dose levels.; Drug: FT819; FT819 will be administered as a single-dose intravenous (IV) infusion at planned dose levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs)	The number of participants with TEAEs will be reported.	Up to approximately 2 years
Number of participants with serious TEAEs	The number of participants with serious TEAEs will be reported.	Up to approximately 2 years
Number of participants with adverse events of special interest (AESI)	The number of participants with AESIs will be reported.	Up to approximately 2 years
Number of participants with TEAEs by severity	The number of participants with TEAEs by severity will be reported. The severity of TEAEs will be determined according to appropriate rating scales for the type of event reported.	Up to approximately 2 years
Number of participants with dose-limiting toxicities (DLTs)	The number of participants with DLTs will be reported.	Up to approximately 29 days
Recommend Phase 2 dose (RP2D) of FT819	The RP2D will be determined.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving definition of remission in SLE (DORIS) complete remission over time	Percentage of participants fulfilling DORIS complete remission at each scheduled assessment and overall will be reported.	Up to approximately 2 years
Percentage of participants achieving DORIS clinical remission over time	Percentage of participants fulfilling DORIS clinical remission at each scheduled assessment and overall will be reported.	Up to approximately 2 years
Percentage of participants achieving lupus low disease activity state (LLDS) over time	Percentage of participants fulfilling LLDS at each scheduled assessment and overall will be reported.	Up to approximately 2 years
Change in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) over time	Change from baseline at each scheduled assessment in SLEDAI-2K will be reported.	Up to approximately 2 years
Change in Physician Global Assessment (PGA) over time	Change from baseline at each scheduled assessment in PGA will be reported.	Up to approximately 2 years
Change in Functional Assessment of Chronic Illness Therapy (FACIT) over time	Change from baseline at each scheduled assessment in FACIT will be reported.	Up to approximately 2 years
Change in estimated glomerular filtration rate (eGFR) over time	Change from baseline at each scheduled assessment in eGFR will be reported.	Up to approximately 2 years
Change in urine creatinine over time	Change from baseline at each scheduled assessment in urine creatinine will be reported.	Up to approximately 2 years
Change in urine protein over time	Change from baseline at each scheduled assessment in urine protein will be reported.	Up to approximately 2 years
Change in protein to creatinine ratio over time	Change from baseline at each scheduled assessment in protein to creatinine ratio will be reported.	Up to approximately 2 years
Concomitant lupus therapies prior to and following study intervention	Incidence of the use of concomitant lupus therapies prior to and following the start of study intervention will be reported.	Up to approximately 2 years
Plasma concentration of FT819	The plasma concentration of FT819 will be determined.	At designated time points up to approximately 29 days

Collaborators and Investigators

• Sponsor: Fate Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2042

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Bendamustine Hydrochloride; Fludarabine
• Other Study ID Numbers: FT819-102

Drug and device information, study documents

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