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

Pilot, Open-Label Study Evaluating the Safety and Feasibility of Using Rescue Therapies for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome

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).

Study Overview

• Status: Recruiting
• Conditions: CRS - Cytokine Release Syndrome; HLH
• Intervention / Treatment: Drug: Tadekinig alfa (IL-18BP)

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: David Porter, MD
      • Contact: Joan Gilmore; Phone Number: 215-573-2540; Email: joan.gilmore@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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: Tadekinig alfa; 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

Drug: Tadekinig alfa (IL-18BP); Tadekinig alfa will be administered via subcutaneous injection. The site of subcutaneous injection should be rotated to avoid injection site reactions; e.g. the outside of the thighs, arms, and the various quadrants of the anterior abdominal wall.; Injection #1/Day 1:o Loading dose of 4 mg/kg; Maximum dose of 350 mg.; Repeat Injection(s): 2 mg/kg/injection; Maximum dose of 160 mg/injection. 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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Shock; Syndrome; Cytokine Release Syndrome
• Other Study ID Numbers: UPCC 01422

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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