Tacrolimus After rATG and Infliximab Induction Immunosuppression (RIMINI)

NCT04114188 | Completed Phase 2 DMC

• 1 other identifier: RIMINI
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

International multicenter open-label single-arm confidence-interval-estimation based Phase II clinical trial, aiming to estimate a plausible range of the proportion of patients experiencing efficacy failure in the population, to provide evidence for efficacy and safety of the induction regimen with rATG and infliximab and a go/no go rule for further clinical development.

Conditions

Renal Transplant Rejection

Keywords

transplant medicine

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of efficacy failure [(treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up) and renal function (estimated glomerular filtration rate)] of the induction regimen

  Composite endpoint of efficacy failure of the induction regimen defined as occurrence of any of the following individual outcomes up to 12 months post transplantation (start of follow up at transplantation): acute rejection, graft loss or poor graft function defined as eGFR\<40 ml/min.

  12 months post transplantation

Secondary Outcomes (12)

• Prevalence of biomarker signatures at 6, 12 months of follow-up.

  6, 12 months of follow-up

• Incidence of death by 12 months post-transplantation

  12 months post-transplantation

• Incidence of graft loss by 12 months post-transplantation

  12 months post-transplantation

• Incidence of metabolic and cardiovascular co-morbidity by 12 months post-transplantation

  12 months post-transplantation

• Proportion of subjects who remain on tacrolimus/steroids therapy at 12 months post-transplantation

  12 months post-transplantation

Study Arms (1)

Antithymocyte Immunoglobulin (Rabbit)

EXPERIMENTAL

rATG induction on day 0 \& 1 post op

Drug: Antithymocyte Immunoglobulin (Rabbit)

Interventions

Antithymocyte Immunoglobulin (Rabbit) DRUG

1st kidney transplant recipients (low risk: PRA/cPRA \< 20%, no DSA) will receive short rATG induction (2x1.5 mg/kg) given perioperatively and on first postoperative day. All patients will receive one shot Infliximab mAb at day 2. Since POD1, maintenance IS consists of Tac and tapered steroids therapy.

Also known as: Infliximab, Tacrolimus, Prednisolone

Antithymocyte Immunoglobulin (Rabbit)

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 XML File Identifier: CJub4EkHas0e/mXDp2mGyZzEe9E= Page 22/33
• Men and women (recipient) age \>18 years and \<70 years
• Panel reactive antibody frequency/ calculated panel reactive antibody frequency (peak PRA/cPRA) \<20%
• Written informed consent
• Diagnosis of end stage renal disease
• Women of Childbearing Potential (WOCBP) must be using a highly effective method of contraception (Pearl-Index \< 1) to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal \[defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL\]. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of clinical trial. Male participants with pregnant or nonpregnant WOCBP partner must use condoms.

You may not qualify if:

• Previous transplantation
• Combined kidney transplantation with other organ
• Subjects receiving an allograft from a donor older than 65 years with elevated serum creatinine levels and/or treated diabetes.
• Immunosuppressive therapy up to 6 months before transplantation
• Planned induction therapy with depletion agents
• EBV seronegativity
• HIV positivity
• Leukopenia \< 3000 cells per microliter, thrombocytopenia \< 100 000 cells per microliter
• Biological therapy history with ATG, OKT3, anti TNF agents
• Tuberculosis history
• Cancer history (skin non-melanoma cancer excluded)
• Anti HCV positivity, HBsAg positivity or HBV DNA positivity
• Detectable donor specific antibodies (DSA) by solid phase assay (Luminex®)
• Subjects with a known hypersensibility to any of the drugs used in this protocol
• Subjects who have used any investigational drug within 30 days prior to enrolment in this clinical trial

Sponsors & Collaborators

• Prof. Dr. Petra Reinke: lead
• Institut Klinické a Experimentální Medicíny: collaborator

Study Sites (1)

Charité University Medicine Berlin

Berlin, 13353, Germany

Location

Related Publications (1)

• Viklicky O, Zahradka I, Bold G, Bestard O, Hruba P, Otto NM, Stein M, Sefrin A, Modos I, Meneghini M, Crespo E, Grinyo J, Volk HD, Christakoudi S, Reinke P. Tacrolimus After rATG and Infliximab Induction Immunosuppression-RIMINI Trial. Transplantation. 2024 Jan 1;108(1):242-251. doi: 10.1097/TP.0000000000004736. Epub 2023 Aug 1.

  PMID: 37525369 DERIVED

MeSH Terms

Interventions

Antilymphocyte Serum; Infliximab; Tacrolimus; Prednisolone

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Antibodies, Monoclonal; Macrolides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Reinke Reinke, PhD, MD

  Charité-University Medicine (Berlin, Germany)

  STUDY CHAIR

• Ondrej Viklicky, PhD, MD

  Institute for Clinical and Experimental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. Petra Reinke, sponsor representative

Model Details: This is a confidence-interval-estimation based early phase design, aiming to estimate a plausible range of the population treatment effect which is not bound to a formal hypothesis.

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 3, 2019
• Study Start: December 15, 2016
• Primary Completion: December 1, 2020
• Study Completion: December 31, 2020
• Last Updated: January 29, 2021

Record last verified: 2021-01

Locations

DE (1)