A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With Systemic Lupus Erythematosus

Status: Recruiting
Location: See location...
Intervention Type: Drug, Biological
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

Primary objective: Safety and tolerability of NKX019, administered after lymphodepletion (LD). Secondary objectives: * Assess clinical activity of NKX019 in subjects with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN) * Characterize pharmacokinetics (PK) of NKX019 * Characterize immunogenicity of NKX019

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 65
Healthy Volunteers: f
View:

• Age: 18-65 years old at the time of informed consent

• Signed informed consent form, able to adhere to the study visit schedule, and comply with other requirements of the study as specified in the protocol

• Score of 8 or more points on the Hybrid-SLEDAI with at least 6 points from clinical items and at least one BILAG A or 2 B

• If SLE and LN: Active nephritis Class III or IV with or without Class V using the 2018 International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria as evidenced on kidney biopsy during screening or within 12 months before study enrollment. Per NIH indices, subjects must have at least activity score ≥ 2 and no more than moderate chronicity index. Subjects must have urinary protein:creatinine ratio (UPCR) ≥ 1.5 g/g or proteinuria ≥ 1.5 g/day, however, subjects must have ≤7g/ day of proteinuria.

• For patients with biopsies older than 6 months we will include an adjudication committee to review clinical data and decide on appropriateness of including the patient (see section 7.3). Additionally, all patients with active LN maximally tolerated doses of renin angiotensin aldosterone system (RAAS) blockade agents, except for patients with contraindications or intolerance to RAAS.

• Women of childbearing potential must have a negative serum pregnancy test at screening and agree to complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study agent until 1 year after the last dose of study agents OR consistent and correct use of acceptable birth control (e.g. levonorgestrel implants, ethinyl estradiol/etonogestrel vaginal ring; injectable progesterone, intrauterine device \[IUD\] with failure rate \< 1% per year, oral contraceptives, double barrier method, transdermal contraceptive patch) OR male partner sterilization with documentation of azoospermia prior to subject's entry into the study.

• Male patients must agree to always use a latex or other synthetic condom during any sexual activity with women of childbearing potential. Male participants must agree to continue to use a condom during the intervention period and for at least 1 year following last treatment with investigational product. Female partners of male participants should be advised to use a highly effective method of contraception during treatment period and at least 12 months following treatment.

• One of the following: positive antinuclear antibodies (ANA) ≥ 1:80 at screening OR positive anti-dsDNA OR positive anti-Smith (anti-Sm) as determined by the local laboratory.

• Refractory SLE defined as having received ≥ 2 prior therapies for SLE (one immunosuppressant and one biologic/advanced therapy) and had an inadequate response to therapy despite being on a therapeutic dose for ≥ 90 days.

• For subjects taking chronic corticosteroids for SLE/LN management, the dose must be stable for ≥ 14 days before screening and cannot exceed 20 mg prednisone/day or equivalent at LD start with planned taper to ≤ 5 mg prednisone by the time of LD start with planned taper to ≤ 5 mg prednisone by the time of the first NKX019 infusion.

• Negative SARS-CoV-2 test.

Locations
United States
New York
Columbia University Irving Medical Center
RECRUITING
New York
Contact Information
Primary
Anca D Askanase, MD, MPH
ada20@cumc.columbia.edu
(212) 305-4308
Time Frame
Start Date: 2024-07-01
Estimated Completion Date: 2040-12
Participants
Target number of participants: 6
Treatments
Experimental: NKX019 infusion
Subjects with SLE will receive cyclophosphamide LD followed by NKX019.
Sponsors
Leads: Columbia University

This content was sourced from clinicaltrials.gov