Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation (NCT NCT00048165)

Last Updated: 2016-06-13

Results Overview

The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months post-transplant (PT). Participants with acute rejection included participants with a biopsy histology of International Society of Heart and Lung Transplant (ISHLT) Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

434 participants

Primary outcome timeframe

Up to 6 months PT

Results posted on

2016-06-13

Participant Flow

The study was conducted across 31 centers in four countries from 28 Aug 1999 to 19 Aug 2002.

Participant milestones

Participant milestones
Measure	Daclizumab Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Completed 6 Months Study STARTED	216	218
Completed 6 Months Study COMPLETED	165	170
Completed 6 Months Study NOT COMPLETED	51	48
Completed 12 Months Study STARTED	165	170
Completed 12 Months Study COMPLETED	162	167
Completed 12 Months Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Daclizumab Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Completed 6 Months Study Administration/Other	8	8
Completed 6 Months Study Abnormality of laboratory test	1	0
Completed 6 Months Study Adverse event/intermittent illness	14	11
Completed 6 Months Study Death	12	6
Completed 6 Months Study Insufficient therapy	1	4
Completed 6 Months Study Other violation	4	6
Completed 6 Months Study Refused treatment	5	5
Completed 6 Months Study Violation criteria	0	2
Completed 6 Months Study Did not receive study drug	6	6
Completed 12 Months Study Administration/Other	0	2
Completed 12 Months Study Death	2	1
Completed 12 Months Study Did not co-operate/Withdrew	1	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an intravenous matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Total n=434 Participants Total of all reporting groups
Age, Continuous	52.4 years STANDARD_DEVIATION 11.75 • n=5 Participants	53.1 years STANDARD_DEVIATION 11.89 • n=7 Participants	52.8 years STANDARD_DEVIATION 11.81 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	41 Participants n=7 Participants	86 Participants n=5 Participants
Sex: Female, Male Male	171 Participants n=5 Participants	177 Participants n=7 Participants	348 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant	77 participants	104 participants

SECONDARY outcome

Timeframe: Up to 12 months PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months. Participants with acute rejection included participants with a biopsy histology of ISHLT Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT	97 participants	116 participants

SECONDARY outcome

Timeframe: Within 6 months and 12 months PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

The number of participants with 0,1, 2, 3 or 4 episodes at 6 and 12 months PT were reported. An episode of acute rejection was defined according to the date of positive biopsy of Grade IIIA or worse or the date of start of treatment for HDC, whichever came first.

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 6 months, 0 episode	139 participants	114 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 6 months, 1 episode	63 participants	82 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 6 months, 2 episodes	12 participants	19 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 6 months, 3 episodes	2 participants	2 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 6 months, 4 episodes	0 participants	1 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 12 months, 0 episode	119 participants	102 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 12 months, 1 episode	68 participants	90 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 12 months, 2 episodes	23 participants	19 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 12 months, 3 episodes	3 participants	5 participants
Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT Within 12 months, 4 episodes	3 participants	2 participants

SECONDARY outcome

Timeframe: At 6 months, 12 months , 3 years PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

The survival of the graft and participants at 6,12 months and 3 years PT was reported

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT Within 6 months	16 participants	10 participants
Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT Within 12 months	21 participants	12 participants
Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT Within 3 years	NA participants Data was not collected	NA participants Data was not collected

SECONDARY outcome

Timeframe: Within 6 months and 12 months PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

The number of participants with Worst International Society of Heart and Lung Transplant (ISHLT) grade within first 6 months and 12 months PT were reported. ISHLT is a standardized grading method to determine the acute cellular rejection on endomyocardial biopsy ; where 0= no rejection, IA= focal (perivascular or interstitial) infiltrate without necrosis, IB= diffuse but sparse infiltrate without necrosis, II=one focus only with aggressive infiltration and/or focal myocyte damage, IIIA=multifocal aggressive infiltrates and/or myocyte damage, IIIB= diffuse inflammatory process with necrosis, IV= diffuse aggressive polymorphous and/or infiltrate and/or edema and/or hemorrhage and/or vasculitis, with necrosis

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade 0	9 participants	5 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade IA	64 participants	51 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade IB	26 participants	28 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade II	55 participants	38 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade IIIA	48 participants	74 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade IIIB	8 participants	15 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 6 months, Grade IV	1 participants	1 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade 0	7 participants	4 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade IA	56 participants	39 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade IB	22 participants	21 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade II	51 participants	47 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade IIIA	63 participants	85 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade IIIB	11 participants	15 participants
Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT Within 12 months, Grade IV	1 participants	1 participants

SECONDARY outcome

Timeframe: Within 6 months and 12 months PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not. The number of participants analyzed for the specified timepoints are denoted by 'n'.

The median time to first acute rejection episode within first 6 months and 12 months PT was reported.

Outcome measures

Outcome measures
Measure	Daclizumab n=97 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=116 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT Within 6 months (n= 77, 104)	61 days Interval 2.0 to 210.0	21 days Interval 1.0 to 240.0
Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT Within 12 months (n=97, 116)	96 days Interval 2.0 to 372.0	26 days Interval 1.0 to 377.0

SECONDARY outcome

Timeframe: Within 6 months and 12 months PT

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

The number of participants who received monomurab Cluster of differentiation 3, orthoclone, polyclonal antithymocyte globulin or antilymphocyte globulin for treatment of biopsy proven rejection or HDC within 6 and 12 months PT were reported.

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=218 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants Using Monomurab Cluster of Differentiation 3, Orthoclone Polyclonal Antithymocyte Globulin or Antilymphocyte Globulin in the First 6 Months and 12 Months PT Within 6 months	17 participants	19 participants
Number of Participants Using Monomurab Cluster of Differentiation 3, Orthoclone Polyclonal Antithymocyte Globulin or Antilymphocyte Globulin in the First 6 Months and 12 Months PT Within 12 months	23 participants	21 participants

SECONDARY outcome

Timeframe: Within 6 months and 12 months PT

The maintenance doses of mycophenolate mofetil (1.5g twice a day daily), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg oral \[PO\]/nasogastric \[NG\] within 72 hours post-operative\]), and cumulative dose of corticosteroids (500-1000 mg IV methylprednisolone pre-operative switched to oral at 0.5-1 mg/kg/day. Tapered to 0.2 mg/kg/d by Day 28, 0.1-0.15 mg/kg/day from Days 36 to 90, and 0.1-0.15 mg/kg/day from Days 120 to 180)at 6 and 12 months PT were reported. Maintenance dose was calculated as total dose per day summed over all days that a participant was administered drug within the specified time interval, divided by number of days that a participant took drug within that time interval.

Outcome measures

Outcome measures
Measure	Daclizumab n=203 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=206 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT MMF dose, 6 months PT (n=193, 201)	2522.2 mg Standard Deviation 791	2450 mg Standard Deviation 748.9
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT MMF dose,12 months PT (n=188, 194)	2394.1 mg Standard Deviation 808	2380.1 mg Standard Deviation 779.2
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT IV Cyclosporine dose, 6 months PT (n=2, 1)	86.11 mg Standard Deviation 102.7	38.1 mg Standard Deviation NA Data not collected
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT IV Cyclosporine dose, 12 months PT (n=4, 2)	93.5 mg Standard Deviation 84.3	46.7 mg Standard Deviation 18
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT PO/NG Cyclosporine dose, 6 months PT (n=184, 182)	321.9 mg Standard Deviation 106.6	331.1 mg Standard Deviation 121.7
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT Cumulative corticosteroids,12 months PT(n=195,200)	1199.6 mg Standard Deviation 771.8	1288.9 mg Standard Deviation 796.1
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT PO/NG Cyclosporine dose, 12 months PT (n=170, 170)	294.7 mg Standard Deviation 93.8	305.7 mg Standard Deviation 116.6
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT Cumulative corticosteroids,6 months PT(n=203, 206)	848.1 mg Standard Deviation 402	955.4 mg Standard Deviation 442.8

SECONDARY outcome

Timeframe: From Baseline (Day -2) to 3 months and 6 months

Lipid profile included total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (all total cholesterol, LDL, HDL, and triglycerides with unit milligram per decilitre \[mg/dL\]), were reported. The median change from baseline (Day -2) in lipid profile values at 3 months and 6 months was reported.

Outcome measures

Outcome measures
Measure	Daclizumab n=126 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=130 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) LDL, Change at 3 months (n=92,89)	0.25 mg/dL Interval -3.35 to 4.84	0.34 mg/dL Interval -2.47 to 3.48
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) Total cholesterol, change at 3 months (n=119,119)	0.65 mg/dL Interval -3.23 to 5.69	0.91 mg/dL Interval -2.2 to 4.53
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) Total cholesterol, change at 6 months (n=126,130)	0.28 mg/dL Interval -3.75 to 6.59	0.61 mg/dL Interval -2.72 to 6.39
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) LDL, Change at 6 months (n=91,99)	0.03 mg/dL Interval -2.86 to 3.98	0.21 mg/dL Interval -2.7 to 3.48
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) HDL, change at 3 months (n=97, 101)	0.34 mg/dL Interval -1.27 to 1.72	0.31 mg/dL Interval -1.48 to 1.64
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) HDL, change at 6 months (n=102,112)	0.23 mg/dL Interval -1.53 to 1.69	0.20 mg/dL Interval -1.3 to 1.17
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) Triglycerides,change at 3 months (n=104,108)	0.26 mg/dL Interval -9.42 to 3.71	0.46 mg/dL Interval -12.5 to 7.84
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) Triglycerides,change at 6 months (n=109,117)	0.20 mg/dL Interval -6.48 to 8.48	0.44 mg/dL Interval -11.3 to 7.21
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) LDL/HDL ratio,change at 3 months (n=91,89)	-0.44 mg/dL Interval -4.33 to 9.41	-0.12 mg/dL Interval -6.73 to 3.53
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) LDL/HDL ratio,change at 6 months (n=91, 99)	-0.50 mg/dL Interval -4.45 to 3.83	-0.14 mg/dL Interval -6.01 to 2.9

SECONDARY outcome

Timeframe: From Baseline (Day -2) to 3 months, and 6 months

Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.

Outcome measures

Outcome measures
Measure	Daclizumab n=91 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=99 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Median Change From Baseline for LDL/HDL Ratio LDL/HDL ratio,change at 6 months (n=91, 99)	-0.50 ratio Interval -4.45 to 3.83	-0.14 ratio Interval -6.01 to 2.9
Median Change From Baseline for LDL/HDL Ratio LDL/HDL ratio,change at 3 months (n=91,89)	-0.44 ratio Interval -4.33 to 9.41	-0.12 ratio Interval -6.73 to 3.53

SECONDARY outcome

Timeframe: Up to 12 months

Population: Safety population included all participants who received at least one dose of study drug (daclizumab or placebo) or commercially available daclizumab and have at least one post-baseline safety assessment (eg. any laboratory data, adverse event, etc). The number of participants analyzed for the specified parameters are denoted by 'n'.

A marked reference range was predefined by Roche. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range (low or high) that also represent a defined change from Baseline were considered marked laboratory abnormalities (i.e. potentially clinically relevant). Hematology included hemoglobin, hematocrit, white blood cell count (WBC) with differential (including granulocytes or neutrophils, basophils, eosinophils, monocytes, lymphocytes), platelets, and erythrocyte count

Outcome measures

Outcome measures
Measure	Daclizumab n=210 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=204 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Hematocrit-high (n=210, 203)	0 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Hematocrit-low (n=210, 203)	116 participants	117 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Hemoglobin-high (n=210, 204)	0 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Hemoglobin-low (n=210, 204)	107 participants	112 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Platelets-high (n=210, 203)	2 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Platelets-low (n=210, 203)	30 participants	22 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters RBC-high (n=209, 203)	1 participants	2 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters RBC-low (n=209, 203)	116 participants	106 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Basophils-high (n=199, 195)	4 participants	4 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Eosinophils-high (n=199, 195)	0 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Lymphocytes-high (n=199, 198)	2 participants	2 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Lymphocytes-low (n=199, 198)	157 participants	157 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Monocytes-high (n=199, 198)	5 participants	6 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Monocytes-low (n=199, 198)	14 participants	20 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters Neutrophils-low (n= 199, 198)	33 participants	33 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters WBC-high (n=207, 201)	61 participants	57 participants
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters WBC-low (n=207, 201)	43 participants	29 participants

SECONDARY outcome

Timeframe: Up to 12 months

A marked reference range was predefined by Roche. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range (low or high) that also represent a defined change from Baseline were considered marked laboratory abnormalities (i.e. potentially clinically relevant). Biochemistry included blood urea nitrogen, creatinine, serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transferase (GGT), phosphorous, total bilirubin, direct bilirubin, total protein, albumin, glucose, alkaline phosphatase, low density lipoprotein (LDH), uric acid, carbon dioxide, magnesium, sodium, potassium, chloride, calcium, LDL, HDL, total cholesterol, and triglycerides.

Outcome measures

Outcome measures
Measure	Daclizumab n=210 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=204 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Creatinine-high (n=211, 203)	66 participants	64 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters SGPT-high (n=200, 200)	48 participants	45 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters ALP-high (n=201, 200)	15 participants	7 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters SGOT-high (n=201, 200)	22 participants	25 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters GGT-high (n=180, 175)	90 participants	74 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters LDH-high (n=194, 191)	53 participants	54 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Total bilirubin-high (n=201, 200)	28 participants	20 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters BUN-high (n= 210, 200)	93 participants	95 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Albumin-low (n=198,197)	47 participants	50 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Total protein-high (n=195,196)	5 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Total protein-low(n=195,196)	85 participants	79 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Cholesterol-high (n=174, 174)	3 participants	4 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Triglycerides-high (n=164, 164)	35 participants	30 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Carbondioxide-high (n=206, 197)	27 participants	21 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Carbondioxide-low (n=206, 197)	12 participants	5 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Chloride-high (n=211, 203)	1 participants	3 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Chloride-low (n=211, 203)	42 participants	36 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Potassium-high (n=211, 204)	7 participants	7 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Potassium-low (n=211, 204)	4 participants	2 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Sodium-high (n=211, 203)	2 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Sodium-low (n=211, 203)	8 participants	11 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Calcium-low (n=207, 201)	39 participants	44 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Glucose fasting-high (n=210, 203)	28 participants	27 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Glucose fasting-low (n=210, 203)	3 participants	3 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Phosphate-high (n=199, 194)	54 participants	48 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Phosphate-low (n=199,194)	32 participants	26 participants
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters Uric acid high (n=191, 188)	23 participants	20 participants

SECONDARY outcome

Timeframe: Up to 12 months

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during this study were reported as AEs. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=207 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal Any AEs	214 participants	207 participants
Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal Any SAE's	108 participants	102 participants
Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal Any AEs leading to premature discontinuation	14 participants	11 participants

SECONDARY outcome

Timeframe: Up to 12 months

The opportunistic infections included infections with Cytomegalovirus, Aspergillus, Candida, Pneumocystis, Cryptococcus, Listeria, Herpes simplex, Herpes zoster. For malignancy, participants with any type of malignancy whose date of onset or diagnosis was after randomization was reported.

Outcome measures

Outcome measures
Measure	Daclizumab n=216 Participants Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.	Placebo n=207 Participants Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram \[mg/kg\]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily \[BID\]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
Number of Participants With Malignancies and Opportunistic Infections Participants with malignancies	11 participants	11 participants
Number of Participants With Malignancies and Opportunistic Infections Participants with opportunistic infections	71 participants	80 participants

Adverse Events

Daclizumab

Serious events: 108 serious events

Other events: 210 other events

Deaths: 0 deaths

Placebo

Serious events: 102 serious events

Other events: 204 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER