Phase 2 N=290 Randomized Triple-blind Treatment

Effects of Inhibiting Early Inflammation in Kidney Transplant Patients

Kidney Transplant

Bottom Line

View on ClinicalTrials.gov: NCT02495077 ↗

Enrolled (actual)

290

Serious AEs

74.8%

Results posted

Aug 2022

Primary outcome: Primary: The Difference Between the Mean eGFR (Modified MDRD) in the Experimental vs. Control Groups. — 52.45; 57.35 mL/min/1.73m2 — p=0.099

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Infliximab (Biological); Methylprednisolone (Drug); Mycophenolate Mofetil (Drug); Tacrolimus (Drug); Thymoglobulin® (Biological); Acetaminophen (Drug); Loratadine (Drug); Placebo for Infliximab (Biological); Prednisone (Drug); Diphenhydramine (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Jul 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY The Difference Between the Mean eGFR (Modified MDRD) in the Experimental vs. Control Groups.	52.45; 57.35	0.099
SECONDARY Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR)	4.2; 3.0	>0.999
SECONDARY Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR).	5.1; 4.2	>0.999
SECONDARY BANFF Grades of First Acute Cellular Rejections (ACR).	1; 1; 1; 0; 1; 1	—
SECONDARY Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) or Borderline Rejection.	8.5; 6.1	0.746
SECONDARY Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) or Borderline Rejection	12.8; 7	0.242
SECONDARY Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection (AMR)	0.0; 0.0	—
SECONDARY Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection (AMR).	1.3; 0.0	>0.999
SECONDARY Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection AMR or Suspicious for AMR	2.8; 0.0	0.497
SECONDARY Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection AMR or Suspicious for AMR.	3.8; 1.4	0.622
SECONDARY BANFF Grades of First AMR.	0; 0	—
SECONDARY Percent of Participants With BANFF Chronicity Scores > or Equal 2 on the 24 Month Biopsy.	73.1; 36.4	0.011 sig
SECONDARY Change in BANFF Chronicity Scores Between Implantation and the 24 Month Biopsy.	4; 6; 6; 6; 9; 2	0.135
SECONDARY Percent of Participants With Locally Treated Rejection, Defined as Treatment Administered for Rejection Based on Clinical Signs or Biopsy Findings.	16.2; 27	0.071
SECONDARY Percent of Participants With Locally Treated Rejection, Defined as Treatment Administered for Rejection Based on Clinical Signs or Biopsy Findings.	16.2; 27	0.071
SECONDARY Change in eGFR Between 3 Months and 24 Months as Measured by MDRD	2.8; 4.8	0.543
SECONDARY Change in eGFR Between 3 Months and 24 Months as Measured by CKD-EPI	2.7; 4.4	0.617
SECONDARY Change in eGFR Between Post-transplant Nadir and 24 Months as Measured by MDRD	8.1; 11.6	0.275
SECONDARY Change in eGFR Between Post-transplant Nadir and 24 Months as Measured by CKD-EPI	8.5; 12.0	0.300
SECONDARY Change in eGFR Between 6 Months and 24 Months as Measured by MDRD	1.0; 5.2	0.152
SECONDARY Change in eGFR Between 6 Months and 24 Months as Measured by CKD-EPI	0.8; 4.8	0.181
SECONDARY eGFR Values as Measured by MDRD	46.64; 48.20; 47.14; 48.99; 47.89; 50.16	0.510
SECONDARY eGFR Values as Measured by MDRD	46.64; 48.20; 47.14; 48.99; 47.89; 50.16	0.510
SECONDARY eGFR Values as Measured by CKD-EPI	49.29; 50.63; 49.80; 51.44; 50.56; 52.65	0.601
SECONDARY eGFR Values as Measured by CKD-EPI	49.29; 50.63; 49.80; 51.44; 50.56; 52.65	0.601
SECONDARY Percent of Participants With Death or Graft Failure.	5.3; 7.1	0.569
SECONDARY Percent of Participants With Only Graft Failure.	2.7; 2.7	>0.999
SECONDARY Percent of Participants That Required at Least One Dialysis Treatment.	31.0; 35.7	0.451
SECONDARY Number of Dialysis Sessions.	0.14; 0.26	0.614
SECONDARY Duration of Delayed Graft Function (DGF), Defined as Time From Transplantation to the Last Required Dialysis Treatment.	13.27; 15.74	0.710
SECONDARY Percent of Participants With Primary Non-Function (PNF), Defined as Dialysis-dependency for More Than 3 Months.	2.8; 0.9	0.622
SECONDARY Change From Baseline (Immediately After Surgery) in Serum Creatinine.	7.35; 6.85; 6.24; 5.87; 5.77; 5.21	0.256
SECONDARY Days From Transplantation Until Event (ACR, AMR, or Hospitalization for Infection and/or Malignancy)	642; 613	0.812
SECONDARY The Percent of Participants With a Serum Creatinine of More Than 3 mg/dL.	47.4; 42.9	0.576
SECONDARY Creatinine Reduction Ratio (CRR), Defined as the First Creatinine on Day 2 Divided by he First Creatinine After Surgery	24.28; 20.97	0.311
SECONDARY Creatinine Reduction Ratio (CRR), Defined as the First Creatinine on Day 5 Divided by the First Creatinine After Surgery.	47.06; 43.37	0.418
SECONDARY The Percent of Participants Whose Day 5 Serum CRR Was Less Than 70%.	74.4; 88.4	0.030 sig
SECONDARY The Percent of Participants Whose Day 2 Serum CRR Was Less Than 30%.	57.1; 68.6	0.153
SECONDARY The Percent of Participants Who Need Dialysis After Week 1.	9.0; 2.8	0.171
SECONDARY Percent of Participants With de Novo DSA.	8.0; 3.6	0.163
SECONDARY Percent of Participants With Any Infection Requiring Hospitalization or Resulting in Death.	43.0; 39.3	0.572
SECONDARY Percent of Participants With Mycobacterial or Fungal Infections	6.1; 6.3	0.973
SECONDARY Percent of Participants With CMV Viremia That Require a Change in Immunosuppression or Anti-viral Treatment as Per Standard of Care at the Site	18.4; 11.6	0.152
SECONDARY Percent of Participants With BK Viremia That Require a Change in Immunosuppression or Anti-viral Treatment as Per Standard of Care at the Site.	28.9; 13.4	0.004 sig
SECONDARY Percent of Participants With Malignancy.	1.8; 0.9	>0.999
SECONDARY Percent of Participants With Impaired Wound Healing Manifested by Wound Dehiscence, Wound Infection, or Hernia at the Site of the Transplant Incision	7.9; 11.6	0.347

Summary

During transplant surgery, there is a period of time when a donated kidney is removed from a donor's body and stored until the time of the transplant surgery. The storage procedure results in buildup of various proteins within the kidney that can injure the donated kidney after it is transplanted. One of these proteins is tumor necrosis factor-alpha (TNF-alpha). The purpose of this study is to evaluate whether taking infliximab, which blocks tumor necrosis factor alpha (TNF-alpha), just prior to transplant surgery, along with usual transplant medicines will protect the donated kidney from damage caused by TNF-alpha and help keep the transplanted kidney healthy for a longer period of time.

Eligibility Criteria

Inclusion Criteria

Adult (>18 years of age) male and female recipients (all races and ethnicities)
Subject must be able to understand and provide consent
Recipients of deceased donor kidney transplants (including re-transplants)
Negative crossmatch, actual or virtual, or a PRA of 0% on historic and current sera as determined by each participating study center
Donor kidneys from deceased donors and donors after cardiac death (DCD) with Kidney Donor Profile Indices (KDPI) ranging from ≥20 to <95
Female participants of childbearing potential must have a negative pregnancy test upon study entry
Subjects must have a negative test result for latent tuberculosis (TB) infection (PPD, QuantiFERON, ELISPOT):
Subjects who have a negative test result for latent TB infection within 1 year of transplant date are eligible for enrollment and no further action is required
Subjects who have a negative test for latent TB infection that is greater than 1 year old are eligible for enrollment but are required to have a repeat test prior to transplantation.

Exclusion Criteria

Inability or unwillingness of a participant to give written informed consent or comply with study protocol
Recipients of living donor transplants
Presence of other transplanted solid organ (heart, lung, liver, pancreas, small intestines) or co-transplanted organ
Human immunodeficiency virus positive (HIV+) recipients
Epstein-Barr virus Immunoglobulin G (EBV IgG) negative recipients
Hepatitis B surface antigen positive kidney transplant recipients
Hepatitis B core antibody positive kidney transplant recipients
Hepatitis B negative kidney transplant recipients that receive transplants from Hepatitis B core antibody positive donor
Hepatitis C Virus positive (HCV+) patients who are either untreated or have failed to demonstrate sustained viral remission for more than 12 months after anti-viral treatment
Recipients with a previous history of active TB
Recipients with a positive test for latent TB infection (PPD, QuantiFERON, ELISPOT), regardless of previous therapy
Any severe infection at the time of transplantation.

--Note: Severe infection determination will be made by the local site investigator.

Severe congestive heart failure (NYHA functional class III or higher)
Subjects with a known hypersensitivity to any murine/ mouse proteins
Subjects with any history of receiving any anti-tumor necrosis factor (anti- TNF) products
Subjects in whom rabbit anti-thymocyte globulin (Thymoglobulin®) or infliximab might not be tolerated
Subjects with a white blood cell count less than 3000/mm^3
Subjects with a platelet count less than 100,000/mm^3
Subjects with systolic blood pressure <100 mm/Hg
Subjects with symptomatic orthostatic hypotension or currently requiring Midodrine for blood pressure support
Subjects from, or who have traveled, to endemic areas with a history of active histoplasmosis or, with a chest x-ray consistent with previous active histoplasmosis (no serological testing required) :

--Endemic regions determined by site based on local standard of care.

Subjects currently or formerly residing in regions of the United States that are highly endemic for coccidioidomycosis, and who have a positive serologic test for coccidioidomycosis:

--Endemic regions determined by site based on local standard of care.

Recipients are excluded if the local site decides to treat the recipient with fluconazole because of diagnosis or suspicion of fungal infection the donor
Subjects that receive IVIG treatment within 3 months of transplant or planned intravenous immunoglobulin (IVIG) treatment peri-transplant
Use of an investigational agent within 4-weeks prior to study entry.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02495077). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.