NCT01596062

Brief Summary

The aims of this study are to extensively study the levels of CD25-Receptors saturation and expression obtained with 2 different doses of Simulect® in combination with Neoral® (i.e to demonstrate that saturation and expression vary according to the dose of Simulect® given), and to study the levels of CD25-Receptors saturation without Neoral® and compare them to the data with Neoral®. It will be conducted in low risk de novo adult renal transplant recipients until 12 weeks post-transplant, receiving either a cumulative dose of 40 or 80 mg of Simulect® in combination with Neoral®, or a cumulative dose of 80 mg of Simulect® in a calcineurin inhibitor free immunosuppressant therapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2012

Shorter than P25 for phase_2

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 29, 2011

Completed
5 months until next milestone

Study Start

First participant enrolled

March 1, 2012

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 10, 2012

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

July 25, 2014

Completed
Last Updated

July 25, 2014

Status Verified

June 1, 2014

Enrollment Period

1 year

First QC Date

September 29, 2011

Results QC Date

March 17, 2014

Last Update Submit

June 26, 2014

Conditions

Keywords

Basiliximabrenal transplantationCNI-freeeverolimus

Outcome Measures

Primary Outcomes (2)

  • Area Under the Curve (AUC) of CD25 Saturation by Basiliximab From Day 0 to Day 84

    CD25 saturation is the percentage of T cells expressing CD25. Mean AUC of CD25 was calculated only for patients who received two Simulect® injections.

    Day 84 (Week 12) after transplantation

  • Saturation Rate of CD25 Antigen Saturation by Basiliximab

    CD25 saturation is the percentage of T cells expressing CD25

    Day 0, Day 1, Day 4, Day 6, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84 (Week 12) post-transplantation

Secondary Outcomes (7)

  • AUC of Basiliximab Binding to CD25 Receptors From Day 0 to Day 84

    Day 84 (Week 12) post-transplantation

  • Percentage of T-cells That Bind Basiliximab to CD25 Receptors

    Day 0, Day 1, Day 4, Day 6, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84 (Week 12) post-transplantation

  • Proportion of CD3+, CD4+, CD8+, CD19+ and CD56+ T Cells

    Day 0, Day 6, Day 42, Day 84 (Week 12)

  • Percentage of Participants With of Biopsy Proven Acute Rejection (BPAR)

    Day 84 (Week 12), Week 24 post-transplantation

  • Percentage of Participants With Biopsy Proven Acute Rejection (BPAR) According to Type and Severity

    Day 84 (Week 12), Week 24 post-transplantation

  • +2 more secondary outcomes

Study Arms (3)

Simulect 40mg + Neoral + Myfortic + steroids

ACTIVE COMPARATOR

A cumulative dose of 40 mg of Simulect® (20mg at Day 0 (D0) and 20mg at Day 4 (D4)+ Neoral® + Myfortic® + corticosteroids

Drug: Simulect®Drug: Neoral®Drug: Myfortic®Drug: Corticosteroids

Simulect 80mg + Neoral + Myfortic + steroids

EXPERIMENTAL

A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Neoral® + Myfortic® + corticosteroids

Drug: Simulect®Drug: Neoral®Drug: Myfortic®Drug: Corticosteroids

Simulect 80mg + Certican + Myfortic + steroids

EXPERIMENTAL

A cumulative dose of 80 mg of Simulect® (40mg at D0 and 40mg at D4) + Certican® + Myfortic® + corticosteroids

Drug: Simulect®Drug: Certican®Drug: Myfortic®Drug: Corticosteroids

Interventions

Simulect® was provided to the study center in its commercial package containing a powder vial with 20 mg of active product and sterile water for injection. The solution should be used immediately after reconstitution. The infusion was prepared by adding at least 50 mL of physiologic or 5% glucose solution to the reconstituted solution (at least 100 mL for 40 mg of Simulect®). Simulect® was transported and kept in a cold environment (2-8°C) as recommended in the summary of product characteristics (SPC).

Also known as: Basiliximab
Simulect 40mg + Neoral + Myfortic + steroidsSimulect 80mg + Certican + Myfortic + steroidsSimulect 80mg + Neoral + Myfortic + steroids

Neoral® was provided to the study center in its commercial package as 10, 25, 50 or 100 mg soft capsules in thermoformed blister packs.

Also known as: Cyclosporine microemulsion
Simulect 40mg + Neoral + Myfortic + steroidsSimulect 80mg + Neoral + Myfortic + steroids

Certican® was provided to the study center in its commercial package as 0.75, 0.5 and 0.25 mg tablets in thermoformed blister packs.

Also known as: Everolimus
Simulect 80mg + Certican + Myfortic + steroids

Myfortic® was administered orally b.i.d. with a 12-hour interval. Tablets could be taken either with or outside meals but consistently throughout the study. To maintain the integrity of the enteric coating, tablets were not to be crushed. Myfortic® treatment was initiated either preoperatively or within 24 hours post transplantation according to local practice in each center. Starting dose was to be 2160 mg/day (1080 mg b.i.d.) for at least 2 weeks and for at most 4 weeks. Patients were then to receive 1440 mg/day (720 mg b.i.d.) until the end of the study. Myfortic® was administered as concomitant treatment to all patients, using the same regimen for all 3 study groups. It was provided to the study center in its commercial package as 180 and 360 mg gastro-resistant tablets.

Also known as: mycophenolate sodium
Simulect 40mg + Neoral + Myfortic + steroidsSimulect 80mg + Certican + Myfortic + steroidsSimulect 80mg + Neoral + Myfortic + steroids

Corticosteroid i.v. therapy could be administered peri or per operatively according to local practice in each center with the same scheme for each patient in the center. Oral corticotherapy was to be initiated rapidly, within one week following transplantation, with a minimal dose of 20 mg/day. Thereafter, the dose was to be decreased according to local practice but oral corticosteroids were to be continued throughout the study with a minimal dose of 5 mg/day.

Simulect 40mg + Neoral + Myfortic + steroidsSimulect 80mg + Certican + Myfortic + steroidsSimulect 80mg + Neoral + Myfortic + steroids

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients receiving a primary renal graft from a deceased or living, related or unrelated donor and who require basiliximab induction therapy
  • Cold ischemia time \< 30 hours
  • Patients undergoing multi-organ transplantation, including both kidneys, or who have previously undergone organ transplantation, including renal transplantation
  • Patients receiving a graft from a non-heart-beating donor
  • A-B-O incompatible graft or positive T cell crossmatch
  • Patients receiving a graft from an expanded criteria donor according to the UNOS definition (donor older than 60 years or donor aged between 50 and 60 years and presence of at least 2 of the following factors: hypertension, serum creatinine concentration ≥ 132 µmol/mL, cardiovascular cause of death)
  • Positive anti-HLA antibodies (Luminex) prior to transplantation
  • Patients whose original renal disease was primary focal and segmental hyalinosis or was related to atypical hemolytic uremic syndrome
  • EBV-negative patients receiving a graft from an EBV-positive donor (EBV D+R-)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Tours, 37044, France

Location

Related Publications (1)

  • Thibault G, Paintaud G, Legendre C, Merville P, Coulon M, Chasseuil E, Ternant D, Rostaing L, Durrbach A, Di Giambattista F, Buchler M, Lebranchu Y. CD25 blockade in kidney transplant patients randomized to standard-dose or high-dose basiliximab with cyclosporine, or high-dose basiliximab in a calcineurin inhibitor-free regimen. Transpl Int. 2016 Feb;29(2):184-95. doi: 10.1111/tri.12688. Epub 2015 Oct 8.

MeSH Terms

Interventions

BasiliximabCyclosporineEverolimusMycophenolic AcidAdrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesSirolimusMacrolidesLactonesOrganic ChemicalsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

Study Officials

  • Novartis Pharmaceticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 29, 2011

First Posted

May 10, 2012

Study Start

March 1, 2012

Primary Completion

March 1, 2013

Study Completion

March 1, 2013

Last Updated

July 25, 2014

Results First Posted

July 25, 2014

Record last verified: 2014-06

Locations