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

• ClinicalTrials.gov Identifier: NCT01843348
• Recruitment Status: Completed
• First Posted: April 30, 2013
• Results First Posted: May 1, 2017
• Last Update Posted: May 1, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: April 18, 2013
• First Posted Date: April 30, 2013
• Results First Submitted Date: March 21, 2017
• Results First Posted Date: May 1, 2017
• Last Update Posted Date: May 1, 2017
• Actual Study Start Date: December 27, 2012
• Actual Primary Completion Date: March 23, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 21, 2017)

Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens [ Time Frame: One year post transplant ]

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

Original Primary Outcome Measures (submitted: April 26, 2013)

GFR mL/min [ Time Frame: one year ]

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 group at month 12 post-transplantation in renal transplant patients.

Current Secondary Outcome Measures (submitted: March 21, 2017)

• Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 [ Time Frame: Month 12 post transplant ]
  Combined endpoint included: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)
• Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant [ Time Frame: Month 12 post transplant ]
  Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method = GFR=141 x min(Scr/κ, 1)α x max(Scr/κ, 1)1.209 x 0.993Age x 1.018 [if female] x 1.159 [if black] where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
• Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant [ Time Frame: Month 12 post transplant ]
  Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
• Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant [ Time Frame: Month 12 post transplant ]
  Modification of Diet in Renal Disease (MDRD) = For men: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x (albumin0,318) For women: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x albumin0,318) x 0.762 with urea nitrogen = urea / 2.144. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
• Percentage of Participants With Treatment Failure Endpoints at Month 12 [ Time Frame: Month 12 post transplant ]
  Treatment failure endpoints: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)
• Percent of Participants With Delayed Graft Function and Slow Graft Function [ Time Frame: Post transplant to month 12 ]
  Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function (SGF) was defined as a serum creatinine >3.0 mg/dL at Day 5 post-transplantation. Full analysis set
• Percent of Participants With Delayed Graft Function by Day [ Time Frame: Post transplant up to day 7 ]
  Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day.
• Percent of Participants With Viral Infections [ Time Frame: Post transplant to month 12 ]
  Viral infections for BKV Virus Humane Polyomavirus 1 and Cytomegalovirus
• Percent of Participants With Wound Healing Complications During Study [ Time Frame: Post transplant until individual reporting ]
  Information collected to report wound healing process which included percentage of participants with complications, fluid collections detected and occurrence of lymphoceles
• Duration of Wound Healing [ Time Frame: Post transplant until individual reporting ]
  A wound will be considered healed if all the suture material and staples are removed and the wound is intact. Number of participants is based on all patients of the respective treatment group in the safety set, excluding patients with no answer (unknown).

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 12 Month Athena Study: Everolimus vs. Standard Regimen in de Novo Kidney Transplant Patients
• Official Title: 12 Month, Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Certican® Based Regimen Either in Combination With Cyclosporin A or Tacrolimus
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Kidney Transplantation
• Renal Transplantation

Intervention

• Drug: Everolimus
  Other Name: Certican
• Drug: Tacrolimus
  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
• Drug: Cyclosporin A
  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
• Drug: Enteric Coated Mycophenolate Sodium (EC-MPS)
  Tablets: 180 mg or 360 mg. Dosing: duration of study 360 mg bid and no less than 360 mg daily dose
• Drug: Mycophenolate mofetil (MMF)
  Capsules: 250 or 500 mg. Dosing: duration of study 500 mg bid and no less than 500 mg total daily dose
• Drug: Corticosteroids
  A minimum dose of 5 mg prednisolon or equivalent
• Drug: Simulect
  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.
  Other Name: Basiliximab

Study Arms

• Active Comparator: TAC+MPA
  Interventions:

  • Drug: Tacrolimus
  • Drug: Enteric Coated Mycophenolate Sodium (EC-MPS)
  • Drug: Mycophenolate mofetil (MMF)
  • Drug: Corticosteroids
  • Drug: Simulect
• Experimental: TAC+Certican
  Interventions:

  • Drug: Everolimus
  • Drug: Tacrolimus
  • Drug: Corticosteroids
  • Drug: Simulect
• Experimental: CycA+Certican
  Interventions:

  • Drug: Everolimus
  • Drug: Cyclosporin A
  • Drug: Corticosteroids
  • Drug: Simulect

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 26, 2013): 612
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 23, 2016
• Actual Primary Completion Date: March 23, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

--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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany

Administrative Information

• NCT Number: NCT01843348
• Other Study ID Numbers: CRAD001ADE44; 2011-005238-21 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: March 2017