INTERCEPT Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

24 May 2021 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Vetenskapsrådet

External identifiers

EU CT number

2024-510615-29-00

EudraCT number

2019-004302-10

ClinicalTrials.gov

NCT04561986

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of this study is to evaluate the efficacy of addition of TCZ to SOC as compared to SOC alone in slowing the decline of graft function from baseline at 24 months after start of treatment as assessed by estimated glomerular filtration rate (eGFR) in kidney transplant recipients with late/chronic active AMR.

Secondary objectives 13

1. To compare the efficacy between the treatment regimens by assessing the differences from baseline in the composite iBox risk prediction score at 12 and 24 months after start of treatment
2. To assess the safety of TCZ for the treatment of late/chronic active AMR during 24 months of treatment period
3. To compare the efficacy between the treatment regimens by assessing the differences from baseline in Evolution of DSA and its strength (mean fluorescence intensity, MFI) at 12, 24 and 36 months
4. To compare the efficacy between the treatment regimens by assessing the differences from baseline in Graft histology at 12 and 24 months
5. To compare the efficacy between the treatment regimens by assessing the differences from baseline in Proteinuria at 12, 24 and 36 months
6. To compare the efficacy between the treatment regimens by assessing the differences from baseline in Renal function assessed by measured GFR (mGFR) at 12, 24 and 36 months
7. To compare the efficacy between the treatment regimens by assessing the differences from baseline in Renal function assessed by eGFR at 12 and 36 months
8. To compare the efficacy between the treatment regimens by assessing the differences from baseline in Patient survival at 12, 24 and 36 months
9. To compare the efficacy between the tretment regimens by assessing the differences from baseline in overall and death-censored graft survival at 12, 24 and 36 months
10. To compare the efficacy between the treatment regimens by assessing the differences from baseline in incidence of acute rejection (overall and by biopsy-proven/clinical diagnosis), its type and Banff-grade if biopsy-proven at 12, 24 and 36 months after start of treatment
11. To compare the efficacy between the treatment regimens by assessing the differences from baseline in incidence and Banff-grade of new chronic active T-cell mediated rejection at 12, 24 and 36 months after start of treatment
12. To assess transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection in the included patients at baseline, 12, 24 and 36 moths, and possibly changes from baseline at each timepoint as well as comparison with other transplant recipients not suffering from AMR
13. To identify differences is responsiveness and adherence to immunosuppressive treatment, symptom burden and transplant-specific well-being in the included patients in relation to age, sex, occupation, civil status, educational status and type of treatment arm, and fear of graft rejection in relation to biopsy or type of treatment arm at baseline, 12, 24 and 36 months as well as in comparison with other transplant recipients not suffering from AMR

Conditions and MedDRA coding

Chronic active antibody-mediated rejection in kidney transplant recipients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. The subject has given their written informed consent to participate in the trial.
2. Recipient of living donor or deceased donor kidney transplant
3. Age ≥18 years
4. At least 6 months post-transplantation at randomization
5. Biopsy-proven diagnosis of late active (≥ 6 months posttransplant) or chronic active AMR according to the Banff 2022 criteria in index biopsy [Repeat biopsy and DSA-testing if required for diagnosis should be performed 2 months ± 2 weeks if the patient has received any treatment for AMR after the initial diagnostic biopsy or at randomization if the last biopsy is older than 12 months (+ 2 weeks) at randomization (Visit 2)].
6. eGFR ≥20 ml/min/1.73 m2 (not older than 1 month at randomization).
7. EBV IgG-positive
8. For female participants of childbearing potential: use of adequate contraception and a negative pregnancy test
9. Subject known to have been previously had COVID-19 must meet the following conditions: • Asymptomatic for at least 1 month before screening visit • Re-established on background immunosuppressants for at least 1 month prior to randomization

Exclusion criteria 20

1. Recipient of multi-organ transplants
2. De novo or recurrent renal disease, if it is considered to be the predominant cause of the current graft dysfunction
3. Active viral infections such as BK virus (BKV), cytomegalovirus (CMV), SARS COV-2 (COVID-19), EBV, hepatitis C virus (HCV) or hepatitis B virus (HBV) infections, based on polymerase chain reaction (PCR) testing
4. Ongoing serious infections as per Investigator’s opinion
5. History of recurrent serious infections requiring hospitalization
6. Signs of post-transplant lymphoproliferative disorder
7. Active tuberculosis (TB)
8. Untreated latent TB (positive QuantiFERON-TB-Gold test, Chest X-ray)
9. Abnormal liver function tests alanine transaminase (ALT), aspartate transaminase (AST), bilirubin > 1.5 x upper limit of normal)
10. Other significant liver disease as per Investigator’s opinion
11. Neutropenia (<2 x109/L) or thrombocytopenia (<100 x109/L)
12. Signs of malignancy. Exceptions are basal cell carcinoma/squamous cell carcinoma or non-malignant melanoma
13. History of malignancy, unless subject has been considered to have fully recovered from malignancy since > 2 years, without any signs of relapse
14. History of diverticulitis, inflammatory bowel disease (IBD) or gastrointestinal perforation
15. Ongoing alcohol or illicit substance abuse
16. Serious medical or psychiatric illness likely to interfere with participation in the study as per Investigator’s opinion
17. Mental inability or reluctance that result in difficulties in understanding the meaning of study participation
18. Woman of childbearing potential who is unwilling/unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of trial drug
19. Woman with a positive pregnancy test or who is pregnant or breastfeeding
20. Current or recent (within last 3 months) participation in another clinical drug trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is mean rate of change in eGFR decline from baseline to 24 months after start of treatment and at 1 month, then every 3 months for 36 months, and evaluating the results as a continuous variable using Modification of Diet for Renal Disease (MDRD) 4-variable equation, as it has been shown to better predict kidney function in kidney transplant recipients especially at low level of kidney function. Testing will be performed directly by accredited chemistry laboratories

Secondary endpoints 13

1. Change from baseline in mean composite iBox risk score at 12 and 24 months after start of treatment
2. Safety: incidence, nature and severity of adverse events (AE) and serious AE (SAE) during 24 months of treatment period
3. Evolution of DSA, as assessed by appearance of new DSA, and change in strength of both immunodominant (iDSA) and cumulative DSA (cDSA), measured as MFI, from baseline at 12, 24 and 36 months after start of treatment
4. Histologic changes from baseline in protocol biopsy at 12 and 24 months after start of treatment
5. Changes from baseline in proteinuria at 12, 24 and 36 months after start of treatment, as assessed by urine albumin/creatinine ratio (UACR)
6. Changes from baseline in renal function at 12, 24 and 36 months after start of treatment, as assessed by mGFR using iohexol clearance
7. Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR
8. Incidence of patient survival at 12, 24 and 36 months after start of treatment
9. Incidence of graft survival (overall and death-censored) at 12, 24 and 36 months after start of treatment
10. Incidence of acute rejection (overall and by biopsy‐proven/clinical diagnosis), its type and Banff-grade if biopsy-proven at 12, 24 and 36 months after start of treatment
11. Incidence and Banff-grade of new chronic active T-cell mediated rejection at 12, 24 and 36 months after start of treatment
12. Experienced transplant-specific well-being, symptom burden, perceived threat of the risk of graft rejection and adherence to immunosuppressive medications at baseline,12, 24 and 36 months after start of treatment, and possible changes from baseline at each time-point as well as in comparison with other transplant recipients not suffering
13. Sex-, occupation-, civil- and educational status-related differences in transplant-specific well-being, symptom burden, perceived threat of the risk of graft rejection and adherence to immunosuppressive medications at baseline, 12, 24 and 36 months as well as in comparison with other transplant recipients not suffering

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Seema Baid-Agrawal

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Seema Baid-Agrawal

Locations

2 EU/EEA countries · 7 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 13 files

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

Application history

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