Tadekinig Alfa for Cytokine Release Syndrome

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Pennsylvania

Disqualifiers: Pregnant, Nursing, Hypersensitivity, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Tadekinig alfa for treating cytokine release syndrome?

Research shows that IL-18 binding protein, the active component in Tadekinig alfa, effectively blocks IL-18, a molecule involved in inflammation, by forming a strong bond with it. This has been demonstrated to reduce inflammation in conditions like sepsis, suggesting it may help manage cytokine release syndrome by reducing excessive inflammatory responses. ^{1 2 3 4 5}

Is Tadekinig Alfa (IL-18BP) generally safe for humans?

Research on IL-18 binding protein, including studies on mice, suggests it is generally safe, as transgenic mice with high levels of IL-18BP showed no tissue or organ abnormalities and were protected against inflammatory stimuli. ^{2 5 6 7 8}

How does the drug Tadekinig Alfa work differently for cytokine release syndrome?

Tadekinig Alfa is unique because it targets and neutralizes interleukin-18 (IL-18), a protein involved in inflammation, by using a binding protein that acts as a decoy receptor. This approach is different from other treatments as it specifically prevents IL-18 from interacting with its receptor, reducing inflammation without affecting other pathways. ^{2 3 6 9 10}

Research Team

Eligibility Criteria

This trial is for adults over 18 who are already part of a University of Pennsylvania CAR T cell study. They must be able to have children and agree to use birth control as described in the protocol. Pregnant or nursing women, or those allergic to the drug's ingredients, cannot join.

Inclusion Criteria

Signed, written informed consent

Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol

I am 18 years old or older.

Exclusion Criteria

Known hypersensitivity to the active substance or one of the excipients of the investigational product(s)

Pregnant or nursing (lactating) women

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tadekinig alfa injections as rescue therapy for CAR T cell related CRS and HLH-like syndrome

5 days

3 visits (in-person)

Continued Dosing (Optional)

Continued dosing approximately every 48-72 hours if the subject is responsive to initial therapy but has ongoing symptoms

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Treatment Details

Interventions

• Tadekinig alfa (IL-18BP) (Interleukin Inhibitor)

Trial Overview The study is testing Tadekinig alfa (IL-18BP) as a rescue therapy for severe immune reactions called CRS and HLH-like syndrome that can happen after CAR T cell treatments. It's an early-stage trial to see if it's safe and workable.

Participant Groups

Group I: Tadekinig alfa Experimental Treatment 1 Intervention

* 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Pennsylvania Philadelphia, PA

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2118

Patients Recruited

45,270,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cloning and expression of interleukin-18 binding protein. Aizawa, Y., Akita, K., Taniai, M., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the functional epitopes of human interleukin-18-binding protein by site-directed mutagenesis. Xiang, Y., Moss, B.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-18 receptor beta-induced changes in the presentation of IL-18 binding sites affect ligand binding and signal transduction. Wu, C., Sakorafas, P., Miller, R., et al.[2019]

IL-18 binding protein (IL-18BP) effectively inhibits the proinflammatory cytokine IL-18 by forming a stable complex, which is crucial in regulating inflammation, especially in conditions like sepsis.

In septic patients, serum levels of IL-18BP were significantly elevated (21.9 ng/ml) compared to healthy individuals (2.15 ng/ml), indicating its potential role in managing IL-18 activity during severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel IL-18BP ELISA shows elevated serum IL-18BP in sepsis and extensive decrease of free IL-18. Novick, D., Schwartsburd, B., Pinkus, R., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Fc-IL-18BPc isoform inhibits IL-18-induced cytokine production. Hong, K., Oh, K., Lee, S., et al.[2012]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-gamma mediates gene expression of IL-18 binding protein in nonleukocytic cells. Mühl, H., Kämpfer, H., Bosmann, M., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Free Bioactive IL-18 and IL-18BP in Inflammatory Disorders. Fauteux-Daniel, S., Girard-Guyonvarc'h, C., Caruso, A., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation and characterization of mice transgenic for human IL-18-binding protein isoform a. Fantuzzi, G., Banda, NK., Guthridge, C., et al.[2008]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases. Park, SY., Hisham, Y., Shin, HM., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting interleukin 18 with interleukin 18 binding protein. Dinarello, CA.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Cloning and expression of interleukin-18 binding protein. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Determination of the functional epitopes of human interleukin-18-binding protein by site-directed mutagenesis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

IL-18 receptor beta-induced changes in the presentation of IL-18 binding sites affect ligand binding and signal transduction. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A novel IL-18BP ELISA shows elevated serum IL-18BP in sepsis and extensive decrease of free IL-18. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Recombinant Fc-IL-18BPc isoform inhibits IL-18-induced cytokine production. [2012]

6. United States pubmed.ncbi.nlm.nih.gov

Interferon-gamma mediates gene expression of IL-18 binding protein in nonleukocytic cells. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Detection of Free Bioactive IL-18 and IL-18BP in Inflammatory Disorders. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Generation and characterization of mice transgenic for human IL-18-binding protein isoform a. [2008]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Targeting interleukin 18 with interleukin 18 binding protein. [2019]