ANCA-Associated Vasculitis (AAV), Idiopathic Inflammatory Myositis (IIM), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc)
Conditions
Keywords
FT839, Fate Therapeutics, Allogenic CAR T, CD19 - targeted therapy, CD38 - targeted therapy, ANCA-associated vasculitis, Rheumatoid arthritis, Systemic sclerosis, Idiopathic inflammatory myositis, Dermatomyositis, Polymyositis
Brief summary
The primary objectives of this trial are to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose of FT839 with or without rituximab and/or background therapy and/or conditioning therapy.
Detailed description
This is a multicenter, Phase 1/2, open-label trial designed to evaluate the safety, pharmacokinetics (PK), anti-B-cell activity, and clinical activity of FT839 in participants with moderate-to-severe ANCA-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). Participants will receive FT839 as monotherapy or in combination with rituximab, with or without conditioning therapy and/or stable background therapy. Participants will be enrolled in 2 stages during the Phase 1 portion of the trial: a dose-escalation stage and a dose-expansion stage. In the dose-escalation stage, safety and tolerability will be assessed to define the MTD (or through the maximum assessed dose \[MAD\] in the absence of dose-limiting toxicities \[DLTs\] defining the MTD). The DLT evaluation period will extend from Day 1 through Day 29. Participants will be followed during the post-treatment follow-up period for up to 2 years after the first dose of FT839, followed by long-term-follow-up for safety and survival for up to 15 years after the first dose of FT839. In the dose-expansion stage, participants will be enrolled into disease-specific cohorts to further evaluate the safety and activity of FT839. Following completion of the Phase 1 portion, the Phase 2 portion of the trial will further evaluate the efficacy of FT839 within each disease cohort.
Interventions
BIOLOGICALFT839
Single Intravenous (IV) infusion of FT839 administered on Day 1 and Day 4
Sponsors
Fate Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 to ≤70 years * Must have active B-cell mediated autoimmune disease (AAV, IIM, RA, SLE, or SSc) confirmed by standard criteria * Moderate to severe disease, requiring at least two prior treatments that were ineffective * Adequate organ function to tolerate treatment * Able to provide informed consent and comply with study procedures
Exclusion criteria
* Diagnosis of more than 1 disease under study (AAV, IIM, RA, SSc, or SLE) or overlap syndrome * Women must not be pregnant or nursing * Severe Organ Dysfunction: Significant heart, lung, liver, or kidney impairment. * Active or chronic infections * Active or recent malignancies * Prior CAR T-cell therapy or organ transplantation * Known allergies to study treatments * Body weight \<45 kg * Active central nervous system (CNS) symptoms attributable to autoimmune disease or nonmalignant CNS disease within 12 months prior to trial intervention * Receipt of any anti-CD19- or anti-CD20-directed therapy within 6 months prior to trial intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Incidence of Dose-limiting Toxicity, Adverse Events, and Serious Adverse Events | From enrollment to the end of the post-treatment follow-up at 2 years | Incidence and severity of dose-limiting Toxicity (DLT)s, adverse event (AE)s, and serious adverse event (SAE)s |
| Phase 2: Change from baseline in Birmingham Vasculitis Activity Score | From enrollment to the end of the post-treatment follow-up at 2 years | Birmingham Vasculitis Activity Score (BVAS) will be measured to evaluate the efficacy of FT839 in AAV. The BVAS score ranges from 0 to 63, with lower scores indicating better outcomes. |
| Phase 2: Change from baseline in Manual muscle testing-8 | From enrollment to the end of the post-treatment follow-up at 2 years | Manual muscle testing-8 (MMT-8) will be measured to evaluate the efficacy of FT839 in IIM. The MMT-8 score ranges from 0 to 150, with higher scores indicating better outcomes. |
| Phase 2: Change from baseline in Disease Activity Score using 28 joint counts and C-reactive protein (a composite measure) | From enrollment to the end of the post-treatment follow-up at 2 years | Disease Activity Score using 28 joint counts and C-reactive protein (DAS28-CRP) will be measured to evaluate the efficacy of FT839 in RA. The validated composite measure DAS28-CRP score ranges from 0.0 to 9.4, with lower scores indicating better outcomes. |
| Phase 2: Change from baseline in SLE Disease Activity Index 2000 | From enrollment to the end of the post-treatment follow-up at 2 years | SLE Disease Activity Index 2000 (SLEDAI-2K) score will be measured to evaluate the efficacy of FT839 in SLE. The SLEDAI-2K score ranges from 0 to 105, with lower scores indicating better outcomes. |
| Phase 2: Change from baseline in Modified Rodnan skin score | From enrollment to the end of the post-treatment follow-up at 2 years | Modified Rodnan skin (mRSS) score will be measured to evaluate the efficacy of FT839 in SSc. The mRSS score ranges from 0 to 51, with lower scores indicating better outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximum concentration and area under the curve of FT839 in peripheral blood | From enrollment to the end of the post-treatment follow-up at 2 years | Pharmacokinetics (PK) of FT839 in peripheral blood including but not limited to maximum concentration (Cmax) and area under the curve (AUC) will be estimated based on observed plasma concentration-time data. |
| Phase 2: Incidence of AEs and SAEs | From enrollment to the end of the post-treatment follow-up at 2 years | Incidence and severity of AEs and SAEs |
| Phase 2: Cmax of FT839 in peripheral blood | From enrollment to the end of the post-treatment follow-up at 2 years | PK of FT839 in peripheral blood including but not limited to Cmax will be estimated based on observed plasma concentration-time data |
| Phase 2: AUC of FT839 in peripheral blood | From enrollment to the end of the post-treatment follow-up at 2 years | PK of FT839 in peripheral blood including AUC will be estimated based on observed plasma concentration-time data |
Countries
United States
Contacts
CONTACTFate Clinical Trials
CONTACTNatalie Shiff, MD
Outcome results
None listed