Tadekinig Alfa for Genetic Autoinflammatory Diseases

No longer recruiting at 13 trial locations

Overseen By Eduardo Schiffrin, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AB2 Bio Ltd.

Must not be taking: Other immunosuppression

Disqualifiers: Malignancy, Infection, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of Tadekinig alfa, a treatment for certain genetic autoinflammatory diseases. These conditions cause the immune system to attack the body, resulting in frequent and painful inflammation. The trial is open to those who participated in a previous study of the same treatment but experienced issues like flare symptoms or required additional medication. Participants must have been part of the prior study and need to wait at least four weeks after stopping the previous treatment before joining this one. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of this treatment.

Will I have to stop taking my current medications?

The trial allows the use of certain medications like NSAIDs, glucocorticoids, cyclosporine, tacrolimus, and IL-1 inhibitors. However, other immunosuppressive medications are not allowed, so you may need to stop those.

Is there any evidence suggesting that Tadekinig alfa is likely to be safe for humans?

Research has shown that Tadekinig alfa has been safe in previous studies. For example, one study tested it on patients with a specific genetic mutation and found that most people tolerated it well. Another study on a different condition also reported good safety results.

Now in a Phase 3 trial, Tadekinig alfa has already passed earlier stages where researchers checked its safety, suggesting it is generally well-tolerated. Prospective participants should note that these findings indicate the treatment has been carefully monitored and reviewed for safety in other studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tadekinig alfa is unique because it works by targeting the interleukin-18 (IL-18) pathway, which is different from most current treatments for genetic autoinflammatory diseases that often focus on blocking other inflammatory cytokines like IL-1 or TNF. This novel mechanism of action might offer a new avenue for those patients who do not respond well to existing therapies. Researchers are excited about Tadekinig alfa because it has the potential to address underlying inflammation more precisely and could lead to better control of symptoms with fewer side effects.

What evidence suggests that Tadekinig alfa might be an effective treatment for genetic autoinflammatory diseases?

In earlier studies, Tadekinig alfa showed promise in treating rare genetic conditions that cause inflammation. Research indicates that Tadekinig alfa, which targets a protein involved in inflammation, is generally safe and shows early signs of effectiveness. It has been studied in conditions like Adult-onset Still's Disease and other inflammatory conditions driven by IL-18. Patients with these conditions experienced reduced inflammation and symptom relief. This trial further tests Tadekinig alfa to ensure its long-term safety and effectiveness in managing pediatric autoinflammatory diseases with specific genetic mutations. ^{1 2 4 5 6}

Who Is on the Research Team?

Eduard Behrens, MD

Principal Investigator

Children Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for patients with specific genetic disorders (NLRC4 mutation or XIAP deficiency) who were in a previous Phase III study and either completed it or needed rescue immunosuppression. They must not have withdrawn voluntarily, be pregnant, or have severe organ issues, life-threatening infections or bleeding, recent live vaccinations, tuberculosis history, or use of certain immunosuppressants.

Inclusion Criteria

Patients must have participated in AB2 Bio ltd. Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) by meeting one of the following mechanisms: a) Completed the first 18-week RCT phase but were not eligible for the RW phase due to flare symptoms. b) Completed the first 18-week RCT phase and RW phase. c) Exited RCT or RW phase due to treatment failure requiring rescue immunosuppression, waiting a minimum of 4 weeks after treatment discontinuation before enrolling in this OLE. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits

Exclusion Criteria

I have not received a live vaccine in the last 3 months.

I have had tuberculosis in the past.

I have not had severe bleeding in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Active drug treatment with Tadekinig alfa for patients with NLRC4 Mutation and XIAP Deficiency

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Long-term safety and tolerability of Tadekinig alfa are evaluated in patients with IL-18 driven monogenic autoinflammatory conditions

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Tadekinig alfa

Trial Overview The trial tests the long-term safety and effectiveness of Tadekinig alfa in children with monogenic autoinflammatory diseases due to NLRC4 mutations/XIAP deficiency. It's an extension for those who've been part of a prior related trial.

How Is the Trial Designed?

Group I: Tadekinig alfa Experimental Treatment 1 Intervention

Active drug treatment during 26 weeks

Who Is Running the Clinical Trial?

AB2 Bio Ltd.

Lead Sponsor

Trials

3

Recruited

50+

Citations

1. clinicaltrials.eu clinicaltrials.eu/trial/study-on-tadekinig-alfa-for-patients-with-nlrc4-mutation-and-xiap-deficiency/

Study on Tadekinig Alfa for Patients with NLRC4 Mutation ... Tadekinig alfa is a medication used in this clinical trial to help manage certain rare genetic conditions that cause inflammation in the body.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02398435

Therapeutic Use of Tadekinig Alfa in Adult-onset Still's ... The objective of this study is to assess safety, tolerability and early signs of efficacy of the investigational drug Tadekinig alfa in Adult-onset Still's ...

3. ab2bio.com ab2bio.com/download/20230307_Press_Release_AB2_Bio_EN_Final.pdf

AB2 Bio Completes Enrolment in Pivotal Phase 3 Trial of ... The study is designed to show the efficacy and safety of Tadekinig alfa (r-hIL-18BP) for the treatment of primary monogenic IL-18 driven HLH, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03113760

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and ... This is a Phase 3 study to assess the safety and efficacy of Tadekinig alfa in patients with monogenic, interleukin-18 (IL 18) driven autoinflammation.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29472362/

Open-label, multicentre, dose-escalating phase II clinical ... Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9553278/

Improving Diagnosis and Clinical Management of Acquired ... A Phase II safety and efficacy trial of tadekinig alfa in AOSD found that both 80 mg and 160 mg, three times a week, had a favourable safety ...