rATG Versus rATG Combined With Intravenous Immunoglobulin (IVIG) Induction Immunosuppression in HLA Incompatible Transplantation (INHIBIT)

NCT04302805 | Completed Phase 3 DMC

• 1 other identifier: Eudra CT: 2019-003723-37
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to prove similar efficacy of PE/rATG (intervention) and PE/rATG/IVIG (centre standard of care) induction regimens to prevent biopsy proven antibody-mediated changes and TCMR as composite endpoint within 12 months after HLA incompatible kidney transplantation.

Conditions

Kidney Transplantation

Keywords

Antibody-mediated rejection; Intravenous immunoglobulin; Rabbit Anti-thymocyte Globulin; Donor specific antibodies

Outcome Measures

Primary Outcomes (1)

• Combined endpoint defined as biopsy proven antibody mediated changes (Banff 2017, Category 2) and/or TCMR (Banff 2017, Category 4) regardless the biopsy indication (for cause or protocol biopsy) in HLAi (HLA incompatible)kidney transplantation

  Number of biopsy-confirmed rejections

  12 months

Secondary Outcomes (16)

• Incidence of active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation

  12 months

• Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation

  12 months

• Incidence of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12

  3 and 12 months

• Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12

  3 and 12 months

• Incidence of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12 post-transplantation

  3 and 12 months

Study Arms (2)

PE/rATG

PLACEBO COMPARATOR

Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg).

Drug: Thymoglobulin; Other: Plasma Exchange

PE/rATG/IVIG

ACTIVE COMPARATOR

Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg) and IVIG 0.5g/kg intravenous infusions, on 1st, 3rd and 5th postoperative day. This is a center standard of care regimen.

Drug: Privigen; Drug: Thymoglobulin; Other: Plasma Exchange

Interventions

Privigen DRUG

Patients randomized to PE/rATG/IVIG group will receive IVIG 0.5g/kg infusions, on 1st, 3rd and 5th postoperative day.

Also known as: IVIG, Kiovig

PE/rATG/IVIG

Thymoglobulin DRUG

All patients will receive 1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg.

Also known as: rATG

PE/rATG; PE/rATG/IVIG

Plasma Exchange OTHER

All patient will undergo Plasma Exchange before transplantation.

Also known as: PE

PE/rATG; PE/rATG/IVIG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary deceased donor or living donor kidney transplantation (first transplantation or re-transplantation)
• Recipient age ≥ 18 years and \< 70 years
• Donor age \< 70 years
• Written Informed Consent and Consent for Processing Personal Data
• Last anti-HLA screening no longer than 12 months with positive results
• MFI DSA 1 000 - 5 000 (anti-HLA A, B, DR), MFI DSA 1000-15000 for anti DQ when available at randomization)

You may not qualify if:

• Combined kidney transplantation with another organ
• Immunosuppressive therapy up to 6 months before transplantation
• AB0i (AB0 incompatible) transplantation
• Women in childbearing potential without adequate contraception
• HIV positivity
• Leukopenia \< 3 000, thrombocytopenia \< 75 000
• Tuberculosis history
• Anti-HCV (Hepatitis C Virus) positivity, HBsAg (Hepatitis B Surface Antigen) positivity or HBV (Hepatitis B Virus) DNA positivity
• DSA (anti A, B, DR) measured by Luminex with MFI \> 5 000 known at screening prior to transplant, anti DQ \> 15000 if known
• FACS (flow-cytometry) T and B crossmatch positivity known at screening prior to transplant
• Positive CDC prior to transplantation
• Planned PP/PE and RTX (Rituximab) treatment post-transplant
• Advanced liver disease (Child-Pugh C or laboratory values of ALT or AST more than 3 times upper limit of normal range)
• Pregnancy, breastfeeding
• Study medication is contraindicated according to the SmPC

Sponsors & Collaborators

• Institute for Clinical and Experimental Medicine: lead

Study Sites (1)

Institute for Clinical and Experimental Medicine

Prague, 140 21, Czechia

Location

Related Publications (1)

• Viklicky O, Zahradka I, Mares J, Slatinska J, Parikova A, Petr V, Roder M, Jaklova K, Osickova K, Janousek L, Hruba P. 12-Month Outcomes of a Prospective Randomized Trial Investigating Effects of IVIG on Top of rATG Versus rATG Alone in Pre-Sensitized Kidney Transplant Recipients: The INHIBIT Study. Transpl Int. 2025 May 19;38:14312. doi: 10.3389/ti.2025.14312. eCollection 2025.

  PMID: 40458542 DERIVED

MeSH Terms

Interventions

Immunoglobulins, Intravenous; thymoglobulin; Plasma Exchange

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Ondrej Viklicky, Prof.

  Institute for Clinical and Experimental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Nephrology and Transplant Center

Model Details: The present study is a prospective randomized single-centre open-label two-arm Phase III.b non-inferiority clinical trial. This trial aims to prove similar efficacy of PE/rATG and PE/rATG/IVIG (centre standard of care) induction regimens to prevent biopsy proven antibody-mediated changes and TCMR as composite endpoint within 12 months after HLA incompatible kidney transplantation.

Study Record Dates

• First Submitted: March 4, 2020
• First Posted: March 10, 2020
• Study Start: July 27, 2020
• Primary Completion: April 15, 2024
• Study Completion: June 15, 2024
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)