Tadekinig Alfa (IL-18BP) Rescue Therapy for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome

Early Phase 1

Recruiting

• Conditions: HLH; CRS - Cytokine Release Syndrome
• Interventions: Drug: Tadekinig alfa (IL-18BP)

• Registration Number: NCT05306080
• Lead Sponsor: University of Pennsylvania

Brief Summary

This is a pilot, open-label study to assess the safety and feasibility of using investigational drug(s) as rescue therapies for CAR T cell related CRS and HLH-like syndrome (CRHLS).

Detailed Description

This pilot, open-label trial will allow for co-enrollment of subjects participating in University of Pennsylvania-Sponsored, CCI-Initiated CAR T cell studies. As utilization of this investigational drug may be required emergently in the event of qualifying safety events post CAR T cell infusion, subjects may be consented/enrolled at the time they receive an investigational CAR T cell product. If/when use of this investigational drug is deemed clinically necessary, rescue therapy may then be initiated.

Cohort 1: Will allow for the use of Tadekinig alfa, an interleukin-18 binding protein that binds and neutralizes IL-18. IL-18 is a key mediator in systemic inflammatory conditions such as MAS/HLH, which may contribute to the severity of CAR T cell-related cytokine release syndrome (CRS) and HLH-like syndrome (CRHLS) and impact response to standard therapy. In addition, subjects experiencing other IL-18 driven toxicity post CAR T cell therapy which is non-responsive to conventional treatment may also receive rescue therapy with Tadekinig alfa as per clinical discretion.

Study Timeline

• Study First Submitted: 2022-03-09
• Study First Submitted QC: 2022-03-30
• Study First Posted: 2022-03-31
• Study Start: 2022-04-17
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-20
• Primary Completion: 2026-01
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Signed, written informed consent
2. Male or female patients age ≥ 18 years
3. Have been co-enrolled in a University of Pennsylvania-Sponsored, CCI-Initiated CAR T cell clinical trial.
4. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol

Exclusion Criteria

1. Pregnant or nursing (lactating) women.
2. Known hypersensitivity to the active substance or one of the excipients of the investigational product(s).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tadekinig alfa	Tadekinig alfa (IL-18BP)	* Injection #1/Day 1: As clinically indicated in accordance with Figure 1.1-1. * Repeat Injection(s): Missed doses will not be made up. * Injection #2/Day 3: Approximately 48 hours (+/- 5 hours) after receipt of the 1st injection. * Injection #3/Day 5: Approximately 48 hours (+/- 5 hours) after receipt of the 2nd injection. * Continued Dosing (Optional): Approximately q48-72 hours; If the subject is responsive to initial therapy, but has ongoing symptoms of CRS/CRHLS. * Retreatment (Optional): May be considered

Primary Outcome Measures

Name	Time	Method
Evaluate preliminary safety and feasibility of administering investigational rescue therapies for the treatment of CAR T cell related CRS and CRHLS.	28 days	Type, frequency, and severity of AEs/SAEs determined to be related to the rescue therapy.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States