Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AB2 Bio S.A.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

9 Oct 2023 → 9 May 2024

Decision date (initial)

2023-07-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504534-21-00

ClinicalTrials.gov

NCT03512314

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

This is an open-label extension study for patients previously enrolled in the preceding clinical trial NLRC4/XIAP.2016.001 to evaluate the long-term safety and tolerability of TA in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP.

Secondary objectives 1

1. Not applicable

Conditions and MedDRA coding

18 driven monogenic autoinflammatory conditions: NLRC4 mutation and XIAP deficiency

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Patients have participated in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953) by one of the following mechanisms: a. Patients that have completed the first 18-week SAOL phase of the preceding clinical trial, but were not eligible for the RW phase due to flare symptoms. b. Patients that completed the first 18-week SAOL phase and completed the RW phase of the preceding clinical trial. c. Patients who have exited either the SAOL 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 of the main study they will be asked to continue with the planned visits of the main study. The time period between participation in the SAOL or RW and the OLE study should not exceed 3 months. After this period, patients are no longer eligible for enrollment into the OLE study.
2. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits (if UPT is positive, a blood test for human chorionic gonadotropin (hCG) to be performed) and who agree to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Birth control methods considered highly effective are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence. In each case of delayed menstrual period (over one month between menstruations, confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. A post-study contraception duration of 4 weeks is recommended taking into account the median half-life of Tadekinig alfa of almost 40h and 5 half-lives representing a duration of 200 hours.

Exclusion criteria 13

1. Patients may not enter the OLE if they voluntarily withdrew from SAOL or RW study or if the time period between participation exceeds 3 months
2. Evidence or history of malignancy
3. Evidence of invasive or life-threatening infection
4. History of tuberculosis
5. Life-threatening bleeding within 2 weeks of screening
6. Vaccination with a live vaccine within the previous 3 months
7. Evidence of severe organ compromise including but not limited to: ▪ Intractable encephalopathy, psychosis, or seizures ▪ Creatinine of > 2X ULN (patients receiving dialysis are also excluded) ▪ Albumin < 1.5 g/dL, ALT>10x ULN, or evidence of acute liver failure ▪ Mechanical ventilation (including invasive and non-invasive forms) ▪ Heart failure requiring medical support including medications ▪ Hypotension from any cause requiring the use of vasopressors
8. Evidence of severe organ compromise including but not limited to: ▪ Intractable encephalopathy, psychosis, or seizures ▪ Creatinine of > 2X ULN (patients receiving dialysis are also excluded) ▪ Albumin < 1.5 g/dL, ALT>10x ULN, or evidence of acute liver failure ▪ Mechanical ventilation (including invasive and non-invasive forms) ▪ Heart failure requiring medical support including medications ▪ Hypotension from any cause requiring the use of vasopressors
9. Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment.
10. Inability to provide informed consent, and also assent if applicable
11. Life expectancy less than 4 weeks
12. Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
13. Hypersensitivity to the active substance or one of the excipients of the investigational product.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability of Tadekinig alfa treatment evaluated by reports of adverse events, abnormal laboratory results, Local tolerability, Immunogenicity evaluation and PK/PD determination

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AB2 Bio S.A.

Sponsor organisation

AB2 Bio S.A.

Address

Building E, Epfl Innovation Park Epfl Innovation Park

City

Lausanne

Postcode

1015

Country

Switzerland

Scientific contact point

Organisation

AB2 Bio S.A.

Contact name

Eduardo Schiffrin

Public contact point

Organisation

AB2 Bio S.A.

Contact name

Eduardo Schiffrin

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications