ARGX-117 in Deceased Donor Kidney Transplant Recipients at Risk for Delayed Graft Function (Varvara)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Argenx

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

15 Feb 2024 → ongoing

Decision date (initial)

2023-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

argenx BV

External identifiers

EU CT number

2022-503091-89-00

ClinicalTrials.gov

NCT05907096

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety, Pharmacodynamic

To evaluate the efficacy of ARGX-117 compared to placebo in improving allograft function in deceased donor kidney transplants at risk for DGF.

Secondary objectives 5

1. To evaluate the efficacy of ARGX-117 compared to placebo to reduce the risk of DGF, promote early recovery, and improve overall allograft function in deceased donor kidney transplants
2. To evaluate the safety and tolerability of ARGX-117 compared to placebo.
3. To assess the PK of ARGX-117.
4. To assess the PD of ARGX-117.
5. To assess the immunogenicity of ARGX-117.

Conditions and MedDRA coding

Delayed graft function

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Is at least the local legal age of consent for clinical studies and at least aged 18 years and less than 70 years when signing the ICF
2. Agree to use contraceptive measures consistent with local regulations.
3. Are diagnosed with ESRD and have been stable on chronic dialysis for at least 3 months.
4. Are recipients of de novo or second-time, single kidney transplant from a deceased donor, either DCD (donation after cardiac/circulatory death) or DBD (donation after brain death).
5. Are ABO compatible with donor allograft, except for type A2 donor to type B recipient kidneys.
6. Have a negative cross match.
7. Have received pretransplant vaccinations for: Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, or are willing to receive the vaccinations approximately 3 to 4 months posttransplant.

Exclusion criteria 10

1. Any history of prothrombotic disorder, or history of thrombosis or hypercoagulable state, excluding vascular access clotting
2. Any known history of complement deficiency.
3. Evidence of peritonitis in participants on peritoneal dialysis.
4. Received any solid organ, bone marrow, or hematopoietic stem cell transplant, with the exception of prior first kidney transplant.
5. High risk within the study period for recurrence of underlying renal disease in the opinion of the investigator.
6. Clinically significant comorbidity, recent major surgery (within 3 months of screening), history of any treatment nonadherence, or intention to have surgery during the study other than kidney transplantation; or any other medical condition that, in the investigator’s opinion, would confound the results of the study or put the participant at undue risk.
7. Clinically significant active bacterial, viral, or fungal infection.
8. History of malignancy unless considered cured by adequate treatment, with no evidence of recurrence for 5 years or more before first study drug administration. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer; Carcinoma in situ of the cervix;Carcinoma in situ of the breast; Incidental histological finding of prostate cancer.
9. History of current alcohol, drug, or medication abuse as assessed by the investigator
10. Pregnant or lactating state or intention to become pregnant during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. eGFR at 24 weeks posttransplant

Secondary endpoints 14

1. Proportion of participants with DGF
2. Proportion of participants with fDGF
3. Duration of dialysis treatment for DGF within the first 30 days posttransplant (ie, date of last dialysis treatment)
4. CRR at 72 hours posttransplant and on study day 8
5. iBox score at 52 weeks posttransplant
6. Dialysis-free participant survival through 52 weeks posttransplant
7. eGFR at 52 weeks posttransplant
8. Safety outcomes, including AE and AESI incidence, vital sign measurements, clinical laboratory tests
9. Incidence of PNF
10. Serum concentrations and PK parameters for ARGX-117
11. Values and changes from baseline in free C2, total C2, and CH50 activity
12. Incidence and prevalence of ADA against ARGX-117
13. Proportion of participants who have ongoing dialysis requirement at study day 31
14. (Death-censored) allograft survival through 52 weeks posttransplant

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Argenx

Sponsor organisation

Argenx

Address

Industriepark-Zwijnaarde 7

City

Gent

Postcode

9052

Country

Belgium

Scientific contact point

Organisation

Argenx

Contact name

Chief Scientific Officer

Public contact point

Organisation

Argenx

Contact name

Vice President Clinical Development

Third parties 12

Locations

7 EU/EEA countries · 28 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

Documents 56 files

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

Application history

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