12 Month Athena Study: Everolimus vs. Standard Regimen in de Novo Kidney Transplant Patients

NCT01843348 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001ADE442011-005238-21
• Study Type: interventional
• Target: 612
• Locations: 2 countries
• Sites: 27

Brief Summary

This study was designed to evaluate the renal function comparing Certican based immunosuppressive regimens with two different CNIs (Tacrolimus or Cyclosporin A) versus a standard treatment with Mycophenolic Acid and Tacrolimus in de novo renal transplant recipients.

Conditions

Kidney Transplantation; Renal Transplantation

Keywords

Transplant; Renal transplant; Rejection,allograf; Rejection; Xenograft rejection; Host vs graft disease; Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens

  To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) in at least one of the Certican® treatment regimens compared to the standard regimen group at month 12 post-transplantation in renal transplant patients. Nankivell formula: GFR = 6.7/Scr + BW/4 - Surea/2 - 100/(height)² + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The eGFR is expressed in mL/min per 1.73m². If a patient was on dialysis at the time of urea or creatinine assessment, the eGFR was set to 0. Analysis set = per protocol set

  One year post transplant

Secondary Outcomes (10)

• Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12

  Month 12 post transplant

• Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant

  Month 12 post transplant

• Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant

  Month 12 post transplant

• Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant

  Month 12 post transplant

• Percentage of Participants With Treatment Failure Endpoints at Month 12

  Month 12 post transplant

Study Arms (3)

TAC+MPA

ACTIVE COMPARATOR

Drug: Tacrolimus; Drug: Enteric Coated Mycophenolate Sodium (EC-MPS); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids; Drug: Simulect

TAC+Certican

EXPERIMENTAL

Drug: Everolimus; Drug: Tacrolimus; Drug: Corticosteroids; Drug: Simulect

CycA+Certican

EXPERIMENTAL

Drug: Everolimus; Drug: Cyclosporin A; Drug: Corticosteroids; Drug: Simulect

Interventions

Everolimus DRUG

Also known as: Certican

CycA+Certican; TAC+Certican

Tacrolimus DRUG

Capsules: 0.5 mg, 1 mg or 5 mg. Dosing schedule: transplant to month 2: 4-8ng/ml, month 3 to month 12 3-5 ng/ml according to standard blood levels

TAC+Certican; TAC+MPA

Cyclosporin A DRUG

Capsules: 10 mg, 25 mg, 50 mg or 100 mg. Transplantation to month 2: 75 - 125 ng/ml, month 3 to month 12: 50 - 100 ng/ml

CycA+Certican

Enteric Coated Mycophenolate Sodium (EC-MPS) DRUG

Tablets: 180 mg or 360 mg. Dosing: duration of study 360 mg bid and no less than 360 mg daily dose

TAC+MPA

Mycophenolate mofetil (MMF) DRUG

Capsules: 250 or 500 mg. Dosing: duration of study 500 mg bid and no less than 500 mg total daily dose

TAC+MPA

Corticosteroids DRUG

A minimum dose of 5 mg prednisolon or equivalent

CycA+Certican; TAC+Certican; TAC+MPA

Simulect DRUG

Lyophilisate in vials with ampoules of sterile water for injection (5 mL), one vial containing 20 mg lyophilisate given intravenously on the day of transplantation and on day four post-transplantation.

Also known as: Basiliximab

CycA+Certican; TAC+Certican; TAC+MPA

Eligibility Criteria

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

You may qualify if:

• Patient who had received a primary or secondary kidney transplant
• Patients who were willing and from whom written informed consent was obtained
• kidney allograft with a cold ischemia time (CIT) \< 30 hours
• negative pregnancy test prior to study enrollment

You may not qualify if:

• Multi-organ recipients
• former Graft loss due to immunological reasons
• Patients who received a kidney from a non-heart beating donor
• A-B-0 incompatible transplants
• a current Panel Reactive Antibody (PRA) level of \> 20%
• existing antibodies against the HLA-type of the receiving transplant
• a known hypersensitivity/contraindication to any of the immunosuppressants
• Use of other investigational drugs
• Patients with thrombocytopenia (platelets \< 100,000/mm³), with an absolute neutrophil count of \< 2,000/mm³ or leucopenia (leucocytes \< 3,000/mm³), or hemoglobin \< 8 g/dL
• significant mental illness
• history of malignancy during the last five years
• HIV positive
• uncontrolled hypercholesterolemia or hypertriglyceridemia
• drug or alcohol abuse
• pregnant or breast feeding women

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (27)

Novartis Investigative Site

Poitiers, France, 86000, France

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Brest, 29200, France

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Dijon, 21079, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Lyon, 69437, France

Location

Novartis Investigative Site

Nantes, 44035, France

Location

Novartis Investigative Site

Paris, 75970, France

Location

Novartis Investigative Site

Saint-Priest-en-Jarez, 42277, France

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Aachen, 52074, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Bochum, 44892, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Erlangen, 91052, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Related Publications (2)

• Philippe A, Arns W, Ditt V, Hauser IA, Thaiss F, Sommerer C, Suwelack B, Dragun D, Hillen J, Schiedel C, Elsasser A, Nashan B. Impact of everolimus plus calcineurin inhibitor on formation of non-HLA antibodies and graft outcomes in kidney transplant recipients: 12-month results from the ATHENA substudy. Front Transplant. 2023 Nov 21;2:1273890. doi: 10.3389/frtra.2023.1273890. eCollection 2023.

  PMID: 38993854 DERIVED

• Sommerer C, Suwelack B, Dragun D, Schenker P, Hauser IA, Nashan B, Thaiss F. Design and rationale of the ATHENA study--A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial. Trials. 2016 Feb 17;17:92. doi: 10.1186/s13063-016-1220-9.

  PMID: 26888217 DERIVED

MeSH Terms

Conditions

Rejection, Psychology; Graft vs Host Disease

Interventions

Everolimus; Tacrolimus; Cyclosporine; Mycophenolic Acid; Adrenal Cortex Hormones; Basiliximab

Condition Hierarchy (Ancestors)

Social Behavior; Behavior; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-779-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2013
• First Posted: April 30, 2013
• Study Start: December 27, 2012
• Primary Completion: March 23, 2016
• Study Completion: March 23, 2016
• Last Updated: May 1, 2017
• Results First Posted: May 1, 2017

Record last verified: 2017-03

Locations

DE (15); FR (12)