A Study to Assess Immune Response in Pediatric Kidney Transplant Recipients Treated With Daclizumab (Zenapax)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02576145
• Collaborator: (none)
• Enrollment: 11
• Locations: 5
• Arms: 2
• Duration (Months): 33.1
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will assess whether daclizumab impairs the ability of children receiving a kidney transplant to elicit a primary immune response. The anticipated time on study treatment is 1 day, and the target sample size is 82 individuals.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Biological: DT; Drug: Daclizumab; Biological: KLH	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immune Response to Neoantigen and Recall Antigen in Pediatric Renal Transplant Recipients Treated With the IL-2R Alfa Monoclonal Antibody, Daclizumab (Zenapax®)
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Jan 1, 2006
• Actual Study Completion Date: Jan 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (With Daclizumab Therapy) Participants who were receiving a full course of 5 doses of daclizumab (1 milligram per kilogram [mg/kg]) with Day 1 vaccine administered immediately prior to the fifth dose.	Biological: DT; Diphtheria and Tetanus Toxoid (DT) will be administered intramuscularly as a 1/3 dilution (0.33 flocculation units). The participants will be rechallenged with DT 6 months after Day 29 if failed to show >=1.5 fold increase in lymphocyte proliferative response but have a humoral response.; Drug: Daclizumab; The fifth dose (1 milligram per kilogram [mg/kg]) of daclizumab will be administered in this study to participants who already received four doses (one dose at 1 mg/kg within 24 hours post-transplant and then every other week for 3 doses).; Other Names: Zenapax ; Biological: KLH; KLH will be administered intradermally with a dose of 250 mcg for participants aged 2 to less than 12 years, and 500 mcg for participants aged 12 to 19 years. The participants will be rechallenged with KLH 6 months after Day 29 if failed to show specified increase in lymphocyte proliferative response or humoral response.
Active Comparator: Group B (Post Daclizumab Therapy) Participants who completed a full course of daclizumab therapy in the previous 4 to 18 months.	Biological: DT; Diphtheria and Tetanus Toxoid (DT) will be administered intramuscularly as a 1/3 dilution (0.33 flocculation units). The participants will be rechallenged with DT 6 months after Day 29 if failed to show >=1.5 fold increase in lymphocyte proliferative response but have a humoral response.; Biological: KLH; KLH will be administered intradermally with a dose of 250 mcg for participants aged 2 to less than 12 years, and 500 mcg for participants aged 12 to 19 years. The participants will be rechallenged with KLH 6 months after Day 29 if failed to show specified increase in lymphocyte proliferative response or humoral response.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Developed a Positive Antibody Response (IgG) to Keyhole Limpet Hemocyanin (KLH) Immunization [Baseline and Day 43 or Day 57]

   Positive antibody response was defined as at least a 2-fold increase in antibody concentration on either Day 43 or Day 57 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. All humoral responses were assessed by enzyme-linked immunosorbent assay (ELISA).

Secondary Outcome Measures

1. Number of Participants Who Developed a Positive Cellular Response to KLH Immunization [Baseline, Day 22, Day 29, Day 43, and Day 57]

   Positive cellular response was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on Days 22, 29, 43 or 57. All cellular responses were assessed by BrdU proliferation assay.

2. Number of Participants Who Developed Both a Positive Antibody Response and a Positive Cellular Response to KLH Immunization [Baseline, Day 22, Day 29, Day 43 and Day 57]

   Positive antibody response was defined as at least a 2-fold increase in antibody concentration on either Day 43 or Day 57 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. Positive cellular response was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on Days 22, 29, 43 or 57. All humoral responses were assessed by ELISA and all cellular responses were assessed by BrdU proliferation assay.

3. Number of Participants Who Developed a Positive Humoral Response to Tetanus Toxoid (TT) [Baseline, Day 22, Day 29, Day 43 and Day 57]

   Humoral response to TT was defined as >=1.5 fold increase in antibody concentration from baseline in participants with protective anti-TT IgG level >=0.1 IU/mL. All humoral responses were assessed by ELISA.

4. Number of Participants Who Developed a Positive Cellular Response to Tetanus Toxoid (TT) [Baseline, Day 22, Day 29, Day 43 and Day 57]

   Positive cellular response was defined as an increase in the BrdU percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on days 22, 29, 43 or 57. All cellular responses were assessed by BrdU proliferation assay.

5. Number of Participants Who Developed a Positive Antibody Response to KLH and Positive Cellular Responses to Both KLH and TT Immunizations [Baseline, Day 22, Day 29, Day 43 and Day 57]

   Positive antibody response was defined as at least a 2-fold increase in antibody concentration on either Day 43 or Day 57 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. Positive cellular response was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on Days 22, 29, 43 or 57. All humoral responses were assessed by ELISA and all cellular responses were assessed by BrdU proliferation assay.

6. Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization [Up to Day 252]

   Nonresponders (participants who failed to mount cellular responses to KLH) were rechallenged with KLH 6 months after Day 29 (Day 196). For nonresponders, positive cellular response to KLH was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point up to Day 252. All cellular responses were assessed by BrdU proliferation assay.

7. Number of Tetanus Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Tetanus Response [up to Day 252]

   Nonresponders (participants who mount humoral responses but no cellular responses to tetanus vaccination) were rechallenged with TT 6 months after Day 29 (Day 196). For nonresponders, positive cellular response to TT was defined as an increase in the BrdU percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, at any time point up to Day 252. All cellular responses were assessed by BrdU proliferation assay.

8. Geometric Mean Antibody Concentrations for KLH (IgM and IgG) and TT (IgG) [Screening, Day 22, Day 29, Day 43 and Day 57]

   Due to the small number of participants enrolled in the study, geometric means at Baseline and on Days 22, 29, 43 and 57 were not reported.

9. Mean Percent Expression of 2A3/CD25+ Antibody [Screening, Day 29, Day 57 and Day 168]

   CD25 is an antigen that is present on a subset of peripheral blood lymphocytes. The expression of CD25+ on T cell was investigated using antibody 2A3. Blood samples were drawn for evaluation of CD25+ at screening and on Days 29, 57, and 168.

10. Mean Percent Expression of CD3, CD4, and CD8 [Days 1, 22, 29, 43 and 57]

    Blood samples were obtained for flow activated cell sorter (FACS) analyses of T cell subsets (CD3, CD4, and CD8) on Days 1, 22, 29, 43, and 57. These cells are present on white blood cells and are used as markers to associate cells with immune functions.

11. Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+ [Days 1, 29 and 57]

    Blood samples were obtained for flow activated cell sorter (FACS) analyses of HLA-DR+, CD45RO+ and CD45RA+ on Days 1, 29, and 57. These cells are present on white blood cells and are used as markers to associate cells with immune functions.

12. Percentage of Participants With Positive Antibody Response to KLH Immunization at Month 6 [Month 6]

    Positive antibody response was defined as at least a 2-fold increase in antibody concentration on Month 6 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. All humoral responses were assessed by enzyme-linked immunosorbent assay (ELISA). Due to the small number of participants enrolled in the study, percentage of participants with positive antibody response to KLH immunization at Month 6 was not reported.

13. Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response [Up to Day 252]

    Nonresponders (participants who failed to mount antibody responses to KLH) were rechallenged with KLH 6 months after Day 29 (Day 196). For nonresponders, positive antibody response to KLH was defined as at least a 2-fold increase in antibody concentration at any time point up to Day 252 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. All humoral responses were assessed by enzyme-linked immunosorbent assay (ELISA).

14. Number of Participants With a Positive Delayed Type Hypersensitivity (DTH) Response After KLH Immunization [Day 1 and Day 29]

    DTH skin reactions were assessed 48 hours after each KLH immunization given on Day 1 and on Day 29. A positive response was defined as an induration >=5 mm.

15. Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) [Up to Month 12]

    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary renal transplant recipients between 2 and 19 years of age

• Receiving or have received daclizumab in the previous 4-18 months

• Receiving or have received daclizumab less than (<) 24 hours pretransplant and additional courses every other week

• Single organ recipients (kidney only)

• Previous vaccination with tetanus toxoid (TT) prior to transplant

• Receiving a maintenance immunosuppression regimen of a calcineurin inhibitor, mycophenolate mofetil, and prednisone (or equivalent corticosteroid)

Exclusion Criteria:

• Received intravenous gamma globulin or a TT vaccination since transplant

• Experienced rejection within 3 months of receiving study vaccinations and/or treated with lymphocyte preparation or methylprednisolone to reverse suspected acute rejection within 3 months of receiving study vaccinations

• Received any vaccine within 30 days of receiving study vaccinations

• Received plasmapheresis treatment or growth hormone treatment since transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States	90027-6062
2		Los Angeles	California	United States	90095-1752
3		Indianapolis	Indiana	United States	46202
4		Kansas City	Missouri	United States	64108
5		Portland	Oregon	United States	97201

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02576145
• Other Study ID Numbers: PA16215
• First Posted: Oct 15, 2015
• Last Update Posted: Jan 13, 2016
• Last Verified: Dec 1, 2015

• Additional relevant MeSH terms: Daclizumab

Study Results

Participant Flow

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Period Title: Overall Study
STARTED	6	5
COMPLETED	3	4
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)	Total
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.	Total of all reporting groups
Overall Participants	6	5	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.8 (5.78)	12.6 (4.16)	12.2 (4.87)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	2 40%	4 36.4%
Male	4 66.7%	3 60%	7 63.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Developed a Positive Antibody Response (IgG) to Keyhole Limpet Hemocyanin (KLH) Immunization
Description	Positive antibody response was defined as at least a 2-fold increase in antibody concentration on either Day 43 or Day 57 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. All humoral responses were assessed by enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline and Day 43 or Day 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 2 vaccine doses and had Day 43 and 57 assessments were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	5	5
Number [participants]	2 33.3%	2 40%

2. Secondary Outcome

Title	Number of Participants Who Developed a Positive Cellular Response to KLH Immunization
Description	Positive cellular response was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on Days 22, 29, 43 or 57. All cellular responses were assessed by BrdU proliferation assay.
Time Frame	Baseline, Day 22, Day 29, Day 43, and Day 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	2	5
Number [participants]	1 16.7%	4 80%

3. Secondary Outcome

Title	Number of Participants Who Developed Both a Positive Antibody Response and a Positive Cellular Response to KLH Immunization
Description	Positive antibody response was defined as at least a 2-fold increase in antibody concentration on either Day 43 or Day 57 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. Positive cellular response was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on Days 22, 29, 43 or 57. All humoral responses were assessed by ELISA and all cellular responses were assessed by BrdU proliferation assay.
Time Frame	Baseline, Day 22, Day 29, Day 43 and Day 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	2	5
Number [participants]	1 16.7%	1 20%

4. Secondary Outcome

Title	Number of Participants Who Developed a Positive Humoral Response to Tetanus Toxoid (TT)
Description	Humoral response to TT was defined as >=1.5 fold increase in antibody concentration from baseline in participants with protective anti-TT IgG level >=0.1 IU/mL. All humoral responses were assessed by ELISA.
Time Frame	Baseline, Day 22, Day 29, Day 43 and Day 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	5	4
Number [participants]	3 50%	3 60%

5. Secondary Outcome

Title	Number of Participants Who Developed a Positive Cellular Response to Tetanus Toxoid (TT)
Description	Positive cellular response was defined as an increase in the BrdU percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on days 22, 29, 43 or 57. All cellular responses were assessed by BrdU proliferation assay.
Time Frame	Baseline, Day 22, Day 29, Day 43 and Day 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	3	4
Number [participants]	2 33.3%	3 60%

6. Secondary Outcome

Title	Number of Participants Who Developed a Positive Antibody Response to KLH and Positive Cellular Responses to Both KLH and TT Immunizations
Description	Positive antibody response was defined as at least a 2-fold increase in antibody concentration on either Day 43 or Day 57 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. Positive cellular response was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point on Days 22, 29, 43 or 57. All humoral responses were assessed by ELISA and all cellular responses were assessed by BrdU proliferation assay.
Time Frame	Baseline, Day 22, Day 29, Day 43 and Day 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	1	2
Number [participants]	0 0%	1 20%

7. Secondary Outcome

Title	Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization
Description	Nonresponders (participants who failed to mount cellular responses to KLH) were rechallenged with KLH 6 months after Day 29 (Day 196). For nonresponders, positive cellular response to KLH was defined as an increase in the 5-bromo-2-deoxyuridine (BrdU) percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, on at least one time point up to Day 252. All cellular responses were assessed by BrdU proliferation assay.
Time Frame	Up to Day 252

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 2 vaccine doses were included in this population. Only participants who were KLH cellular nonresponders were evaluated.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	1	1
Number [participants]	0 0%	0 0%

8. Secondary Outcome

Title	Number of Tetanus Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Tetanus Response
Description	Nonresponders (participants who mount humoral responses but no cellular responses to tetanus vaccination) were rechallenged with TT 6 months after Day 29 (Day 196). For nonresponders, positive cellular response to TT was defined as an increase in the BrdU percent total net of at least 1.5-fold compared with baseline, where baseline was assigned a value of 0.5 if <=0, at any time point up to Day 252. All cellular responses were assessed by BrdU proliferation assay.
Time Frame	up to Day 252

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 2 vaccine doses were included in this population. Only participants who were tetanus cellular nonresponders were evaluated.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	1	1
Number [participants]	0 0%	0 0%

9. Secondary Outcome

Title	Geometric Mean Antibody Concentrations for KLH (IgM and IgG) and TT (IgG)
Description	Due to the small number of participants enrolled in the study, geometric means at Baseline and on Days 22, 29, 43 and 57 were not reported.
Time Frame	Screening, Day 22, Day 29, Day 43 and Day 57

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	0	0

10. Secondary Outcome

Title	Mean Percent Expression of 2A3/CD25+ Antibody
Description	CD25 is an antigen that is present on a subset of peripheral blood lymphocytes. The expression of CD25+ on T cell was investigated using antibody 2A3. Blood samples were drawn for evaluation of CD25+ at screening and on Days 29, 57, and 168.
Time Frame	Screening, Day 29, Day 57 and Day 168

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population. Only participants with data available at a particular time point were analyzed.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	6	5
Screening, n=1, 5	0.10 (NA)	9.44 (3.023)
Day 29, n=5, 3	0.12 (0.084)	8.53 (2.003)
Day 57, n=5, 5	0.06 (0.055)	10.18 (2.479)
Day 168, n=6, 3	8.33 (2.670)	12.53 (4.888)

11. Secondary Outcome

Title	Mean Percent Expression of CD3, CD4, and CD8
Description	Blood samples were obtained for flow activated cell sorter (FACS) analyses of T cell subsets (CD3, CD4, and CD8) on Days 1, 22, 29, 43, and 57. These cells are present on white blood cells and are used as markers to associate cells with immune functions.
Time Frame	Days 1, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population. Only participants with data available at a particular time point were analyzed.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	6	5
CD3+, Day 1, n=6, 2	76.97 (4.069)	79.50 (1.414)
CD3+, Day 22, n=6, 2	78.70 (7.211)	77.25 (1.202)
CD3+, Day 29, n=5, 2	79.82 (9.116)	78.80 (1.131)
CD3+, Day 43, n=5, 2	76.74 (10.126)	78.65 (0.778)
CD3+, Day 57, n=5, 2	77.80 (8.460)	79.20 (3.960)
CD4+, Day 1, n=6, 2	48.87 (7.153)	36.90 (7.212)
CD4+, Day 22, n=6, 2	48.98 (7.743)	34.20 (9.051)
CD4+, Day 29, n=5, 2	51.16 (8.830)	34.85 (7.566)
CD4+, Day 43, n=5, 2	47.08 (8.685)	34.75 (6.435)
CD4+, Day 57, n=5, 2	47.58 (8.404)	36.85 (6.718)
CD8+, Day 1, n=6, 2	24.07 (5.452)	37.30 (9.758)
CD8+, Day 22, n=6, 2	25.15 (6.806)	38.25 (11.526)
CD8+, Day 29, n=5, 2	24.06 (7.790)	38.75 (10.394)
CD8+, Day 43, n=5, 2	24.00 (8.405)	39.00 (8.768)
CD8+, Day 57, n=5, 2	24.86 (7.110)	38.55 (11.243)

12. Secondary Outcome

Title	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+
Description	Blood samples were obtained for flow activated cell sorter (FACS) analyses of HLA-DR+, CD45RO+ and CD45RA+ on Days 1, 29, and 57. These cells are present on white blood cells and are used as markers to associate cells with immune functions.
Time Frame	Days 1, 29 and 57

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.Only participants with data available at a particular time point were analyzed.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	6	5
HLADR+, Day 1, n=6, 2	2.58 (1.098)	5.80 (3.394)
HLADR +, Day 29, n=5, 2	5.04 (7.720)	5.10 (4.101)
HLADR +, Day 57, n=5, 2	4.16 (5.126)	4.55 (3.182)
CD45RO +, Day 1, n=6, 2	22.85 (3.690)	39.45 (3.889)
CD45RO +, Day 29, n=5, 2	27.04 (4.779)	39.45 (8.556)
CD45RO +, Day 57, n=5, 2	26.90 (7.027)	34.45 (3.323)
CD45RA +, Day 1, n=6, 2	69.85 (4.359)	50.50 (4.384)
CD45RA +, Day 29, n=5, 2	66.86 (5.663)	52.70 (10.041)
CD45RA +, Day 57, n=5, 2	62.84 (5.999)	56.15 (5.869)

13. Secondary Outcome

Title	Percentage of Participants With Positive Antibody Response to KLH Immunization at Month 6
Description	Positive antibody response was defined as at least a 2-fold increase in antibody concentration on Month 6 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. All humoral responses were assessed by enzyme-linked immunosorbent assay (ELISA). Due to the small number of participants enrolled in the study, percentage of participants with positive antibody response to KLH immunization at Month 6 was not reported.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	0	0

14. Secondary Outcome

Title	Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response
Description	Nonresponders (participants who failed to mount antibody responses to KLH) were rechallenged with KLH 6 months after Day 29 (Day 196). For nonresponders, positive antibody response to KLH was defined as at least a 2-fold increase in antibody concentration at any time point up to Day 252 compared with baseline where baseline was assigned a value of 1 if it was below the limit of quantification. All humoral responses were assessed by enzyme-linked immunosorbent assay (ELISA).
Time Frame	Up to Day 252

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 2 vaccine doses were included in this population. Only participants who were KLH Antibody nonresponders were evaluated.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	2	1
Number [participants]	1 16.7%	1 20%

15. Secondary Outcome

Title	Number of Participants With a Positive Delayed Type Hypersensitivity (DTH) Response After KLH Immunization
Description	DTH skin reactions were assessed 48 hours after each KLH immunization given on Day 1 and on Day 29. A positive response was defined as an induration >=5 mm.
Time Frame	Day 1 and Day 29

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	6	5
Number [participants]	0 0%	1 20%

16. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes
Time Frame	Up to Month 12

Outcome Measure Data

Analysis Population Description

All patient population: All participants who were enrolled in the study and received at least 1 vaccine dose were included in this population.

Arm/Group Title	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.	Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
Measure Participants	6	5
Any AE	6 100%	4 80%
Any SAE	3 50%	2 40%

Adverse Events

Time Frame	Up to Month 12
Adverse Event Reporting Description	SAEs and AEs were collected in members of All Patient Population, comprised of all participants who were enrolled in the study and received at least 1 vaccine dose.
Arm/Group Title	Group A (With Daclizumab Therapy)		Group B (Post Daclizumab Therapy)
Arm/Group Description	Participants who had a renal transplant prior to 6 weeks of study vaccine administration and who were receiving daclizumab therapy were included. Participants were initially vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine at least 30 minutes prior to fifth-dose of daclizumab infusion (i.e. Day 1). The next vaccination with DT and KLH was done on Day 29.		Participants who had a renal transplant and who were within 4 to 18 months of completing daclizumab therapy were included. Participants were vaccinated with Diphtheria Tetanus Toxoid (DT) vaccine and Keyhole Limpet Hemocyanin (KLH) vaccine on Day 1 and Day 29.
All Cause Mortality
	Group A (With Daclizumab Therapy)		Group B (Post Daclizumab Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A (With Daclizumab Therapy)		Group B (Post Daclizumab Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		2/5 (40%)
Infections and infestations
BK virus infection	1/6 (16.7%)		0/5 (0%)
Epstein-Barr virus infection	1/6 (16.7%)		0/5 (0%)
Gastroenteritis	0/6 (0%)		1/5 (20%)
Viral infection	0/6 (0%)		1/5 (20%)
Renal and urinary disorders
Haematuria	1/6 (16.7%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Group A (With Daclizumab Therapy)		Group B (Post Daclizumab Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		4/5 (80%)
Blood and lymphatic system disorders
Leukopenia	3/6 (50%)		0/5 (0%)
Anaemia	0/6 (0%)		1/5 (20%)
Endocrine disorders
Hyperparathyroidism	1/6 (16.7%)		0/5 (0%)
Gastrointestinal disorders
Vomiting	1/6 (16.7%)		1/5 (20%)
Abdominal pain	0/6 (0%)		1/5 (20%)
Diarrhoea	1/6 (16.7%)		0/5 (0%)
Gastrooesophageal reflux disease	1/6 (16.7%)		0/5 (0%)
Ileus	0/6 (0%)		1/5 (20%)
Nausea	1/6 (16.7%)		0/5 (0%)
General disorders
Injection site induration	0/6 (0%)		1/5 (20%)
Oedema peripheral	1/6 (16.7%)		0/5 (0%)
Pyrexia	0/6 (0%)		1/5 (20%)
Infections and infestations
Hordeolum	1/6 (16.7%)		0/5 (0%)
Upper respiratory tract Infection	0/6 (0%)		1/5 (20%)
Bronchitis	1/6 (16.7%)		0/5 (0%)
Gastroenteritis	1/6 (16.7%)		0/5 (0%)
Pneumonia	0/6 (0%)		1/5 (20%)
Rhinitis	0/6 (0%)		1/5 (20%)
Sepsis	1/6 (16.7%)		0/5 (0%)
Urinary tract infection	1/6 (16.7%)		0/5 (0%)
Nasopharyngitis	1/6 (16.7%)		0/5 (0%)
Injury, poisoning and procedural complications
Sunburn	1/6 (16.7%)		0/5 (0%)
Investigations
Blood creatinine increased	1/6 (16.7%)		1/5 (20%)
Urinary sediment present	1/6 (16.7%)		0/5 (0%)
Metabolism and nutrition disorders
Acidosis	0/6 (0%)		1/5 (20%)
Anorexia	0/6 (0%)		1/5 (20%)
Hyperkalaemia	0/6 (0%)		1/5 (20%)
Hypomagnesaemia	1/6 (16.7%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/6 (0%)		1/5 (20%)
Nervous system disorders
Dizziness	0/6 (0%)		1/5 (20%)
Headache	0/6 (0%)		1/5 (20%)
Tremor	1/6 (16.7%)		0/5 (0%)
Renal and urinary disorders
Haematuria	2/6 (33.3%)		0/5 (0%)
Dysuria	1/6 (16.7%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/6 (16.7%)		0/5 (0%)
Cough	0/6 (0%)		1/5 (20%)
Nasal congestion	0/6 (0%)		1/5 (20%)
Pharyngolaryngeal pain	1/6 (16.7%)		0/5 (0%)
Respiratory tract congestion	0/6 (0%)		1/5 (20%)
Rhinorrhoea	0/6 (0%)		1/5 (20%)
Skin and subcutaneous tissue disorders
Acne	0/6 (0%)		1/5 (20%)
Vascular disorders
Hypertension	0/6 (0%)		1/5 (20%)
Hypotension	1/6 (16.7%)		0/5 (0%)
Orthostatic hypotension	1/6 (16.7%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.