XIAP DeficiencyPhase 3NCT03512314
Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency As Open Label Extension
A Phase 3 study testing Tadekinig alfa in people with XIAP Deficiency and NLRC4-MAS, run by AB2 Bio Ltd. at 11 sites in 3 countries.
Trial summary
This is an open-label extension study for patients previously enrolled in the AB2 Bio Ltd. ongoing Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953). This OLE study will evaluate the long-term safety and tolerability of Tadekinig alfa in patients suffering from pediatric monogenic autoinflammatory diseases… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- XIAP Deficiency, NLRC4-MAS
- What is being tested?
- Tadekinig alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 24 Jan 2018to 8 May 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients have participated in AB2 Bio ltd. Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) by one of the following mechanisms : a) Patients that have completed the first 18-week RCT phase of the preceding clinical trial but were not eligible for the RW phase due to flare symptoms. Or b) Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial. Or c) Patients who have exited either the RCT or RW phase of the preceding clinical trial due to treatment failure requiring rescue immunosuppression. Such patients must wait a minimum of 4 weeks after treatment discontinuation from the preceding clinical trial before enrolling in this OLE. If patients do not consent to enroll in the OLE after their early termination in the main study, they will be asked to continue with the planned visits of the main study
- Women of childbearing potential with negative urine pregnancy test (UPT) at all visits
Who cannot join
- Patients may not enter the OLE if they voluntarily withdrew from RCT or RW study or if the time period between participation exceeds 3 months
- Evidence or history of malignancy
- Evidence of invasive or life-threatening infection
- History of tuberculosis
- Life-threatening bleeding within 2 weeks of screening
- Vaccination with a live vaccine within the previous 3 months
Show all 12Show fewer
- Evidence of severe organ compromise including but not limited to: (see details in the protocol)
- Pregnant or breastfeeding females
- Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment.
- Inability to provide informed consent, and also assent if applicable
- Life expectancy less than 4 weeks
- Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States8 sites
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, 30322
Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Shands Children's Hospital
Gainsville, Florida, 32610
Texas Children's Hospital _ Baylor College of Medicine
Houston, Texas, 77030
UCSD _ Department of Pediatrics / Rady Children's Hospital
La Jolla, California, 92056
Children Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Canada2 sites
CHU Sainte-Justine
Montreal
The Hospital for Sick Children
Toronto, Ontario, ON M5G 1X8
Germany1 site
Universitätsklinikum Freiburg, Centrum für Chronische Immundefizienz (CCI) - Paediatric Unit
Freiburg im Breisgau, Baden-Wurttemberg, 79106
About this study
Official title: Open-label Extension Study with Tadekinig Alfa (r-hIL-18BP) to Monitor Safety and Tolerability in Patients with IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency
This is an open-label extension study for patients previously enrolled in the AB2 Bio Ltd. ongoing Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953). This OLE study will evaluate the long-term safety and tolerability of Tadekinig alfa in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP.
Read the detailed description
Pediatric auto-inflammatory conditions related to spontaneous activating mutations of the NLRC4 and with recurrent MAS-like flares with constitutive IL-18 hypersecretion, may require long-term blockade of the IL-18 pathway.
Patients with X-linked inhibitor of apoptosis (XIAP) deficiency and suffering from Hemophagocytic-Lymphohistiocytosis (HLH), a MAS-like syndrome, also show high levels of serum IL-18 and may benefit from IL-18 blockade treatment until a curative hematopoietic stem cell transplantation can be performed The safety of IL-18 blockade during long-term periods is of major interest for the treatment of these patients
- Conditions
- XIAP Deficiency, NLRC4-MAS
- Being tested
- Tadekinig alfa
- Medical subject headings
- Lymphoproliferative Syndrome, X-Linked, 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tadekinig alfaDrug
Also called r-hIL-18BP
Open label, 26 weeks on Tadekinig alfa treatment.
| Study group | Role | What they receive |
|---|---|---|
| Tadekinig alfa | Experimental | Active drug treatment during 26 weeks Receives: Drug: Tadekinig alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reports of adverse events
The incidence, nature and severity of AEs will be reported
Measured: 26 weeks
Reports of abnormal physical examination
Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0.
Measured: 26 weeks
Reports of abnormal laboratory results
Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results
Measured: 26 weeks
Immunogenicity evaluation
Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
Measured: 26 weeks
Evaluation of the local tolerability at the injection site
Evaluation will be done based on the Local Tolerability Index where the patients will be asked to assess the degree of pain, redness, swelling, bruising, tenderness and itching, they are experiencing from each injection.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2018
- Study start24 Jan 2018
- Primary completion8 Apr 2024
- Study completion8 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for XIAP DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- AB2 Bio Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eduard Behrens, MD, Principal investigator, Children Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03512314
- Sponsor's protocol ID
- OLE-NLRC4/XIAP.2016.001
- Status last verified
- Jan 2025
- First submitted
- 9 Apr 2018
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: This information will be provided soon
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Extension Study with Tadekinig Alfa (r-hIL-18BP) to Monitor Safety and Tolerability in Patients with IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency
- ClinicalTrials.gov ID
- NCT03512314
- Acronym / sponsor ID
- OLE-NLRC4/XIAP.2016.001
- Conditions
- XIAP Deficiency, NLRC4-MAS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- AB2 Bio Ltd.Industry (pharma, biotech, devices)
- Study start
- 24 Jan 2018 (actual)
- Primary completion
- 8 Apr 2024 (actual)
- Study completion
- 8 May 2024 (actual)
- First posted
- 30 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label extension study for patients previously enrolled in the AB2 Bio Ltd. ongoing Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953). This OLE study will evaluate the long-term safety and tolerability of Tadekinig alfa in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP.
Detailed description
Pediatric auto-inflammatory conditions related to spontaneous activating mutations of the NLRC4 and with recurrent MAS-like flares with constitutive IL-18 hypersecretion, may require long-term blockade of the IL-18 pathway.
Patients with X-linked inhibitor of apoptosis (XIAP) deficiency and suffering from Hemophagocytic-Lymphohistiocytosis (HLH), a MAS-like syndrome, also show high levels of serum IL-18 and may benefit from IL-18 blockade treatment until a curative hematopoietic stem cell transplantation can be performed The safety of IL-18 blockade during long-term periods is of major interest for the treatment of these patients
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tadekinig alfa | Experimental | Drug: Tadekinig alfaActive drug treatment during 26 weeks |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients have participated in AB2 Bio ltd. Phase III clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) by one of the following mechanisms : a) Patients that have completed the first 18-week RCT phase of the preceding clinical trial but were not eligible for the RW phase due to flare symptoms. Or b) Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial. Or c) Patients who have exited either the RCT or RW phase of the preceding clinical trial due to treatment failure requiring rescue immunosuppression. Such patients must wait a minimum of 4 weeks after treatment discontinuation from the preceding clinical trial before enrolling in this OLE. If patients do not consent to enroll in the OLE after their early termination in the main study, they will be asked to continue with the planned visits of the main study
- Women of childbearing potential with negative urine pregnancy test (UPT) at all visits
Key exclusion criteria (12 listed)
- Patients may not enter the OLE if they voluntarily withdrew from RCT or RW study or if the time period between participation exceeds 3 months
- Evidence or history of malignancy
- Evidence of invasive or life-threatening infection
- History of tuberculosis
- Life-threatening bleeding within 2 weeks of screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tadekinig alfaAlso: r-hIL-18BPOpen label, 26 weeks on Tadekinig alfa treatment. | Drug | Tadekinig alfa |
Primary outcome
Reports of adverse events
Time frame: 26 weeks
The incidence, nature and severity of AEs will be reported
Reports of abnormal physical examination
Time frame: 26 weeks
Measurements will be done using the modified Auto-inflammatory Disease Activity Index (mAIDAI) including multiple measurements aggregated as 1 / 0.
Reports of abnormal laboratory results
Time frame: 26 weeks
Report of clinically significant abnormal laboratory results (i.eSerum CRP (ug/mL), Serum Ferritin (ng/mL). and any other abnormal lab results
Immunogenicity evaluation
Time frame: 26 weeks
Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
Evaluation of the local tolerability at the injection site
Time frame: 26 weeks
Evaluation will be done based on the Local Tolerability Index where the patients will be asked to assess the degree of pain, redness, swelling, bruising, tenderness and itching, they are experiencing from each injection.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Individual participant dataSharing planned: Undecided. This information will be provided soon
Related trials for XIAP Deficiency
Active, not recruitingPhase 2
Study to Evaluate the Efficacy, Safety and Tolerability of MAS825 in Patients With Monogenic IL-18 Driven Autoinflammatory Diseases, Including NLRC4-GOF, XIAP Deficiency, or CDC42 Mutations
NLRC4-GOF, AIFEC (Autoinflammation With Infantile Enterocolitis), XIAP Deficiency, CDC42 Mutations
RecruitingPhase 1
Quercetin in Patients With XIAP (X-linked Inhibitor of Apoptosis) Deficiency
XIAP Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eduard Behrens, MD principal investigator
Children Hospital of Philadelphia
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tadekinig alfa in people with XIAP Deficiency and NLRC4-MAS, run by AB2 Bio Ltd. at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reports of adverse events (time frame: 26 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.