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

Immune Response to Neoantigen and Recall Antigen in Pediatric Renal Transplant Recipients Treated With the IL-2R Alfa Monoclonal Antibody, Daclizumab (Zenapax®)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02576145

Enrollment

Registered

2015-10-15

Start date

2003-04-30

Completion date

2006-01-31

Last updated

2016-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Transplantation

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.

Interventions

BIOLOGICALDT

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.

DRUGDaclizumab

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).

BIOLOGICALKLH

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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 19 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Group A (With Daclizumab Therapy) 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.	6
Group B (Post Daclizumab Therapy) 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.	5
Total	11

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Acute rejection	1	0
Overall Study	Adverse Event	1	0
Overall Study	Tetanus Titers Decreased	0	1
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Group A (With Daclizumab Therapy)	Group B (Post Daclizumab Therapy)	Total
Age, Continuous	11.8 years STANDARD_DEVIATION 5.78	12.6 years STANDARD_DEVIATION 4.16	12.2 years STANDARD_DEVIATION 4.87
Sex: Female, Male Female	2 Participants	2 Participants	4 Participants
Sex: Female, Male Male	4 Participants	3 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	6 / 6	4 / 5
serious Total, serious adverse events	3 / 6	2 / 5

Outcome results

Primary

Number of Participants Who Developed a Positive Antibody Response (IgG) to Keyhole Limpet Hemocyanin (KLH) Immunization

Time frame: Baseline and Day 43 or Day 57

Population: 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	Measure	Value (NUMBER)
Group A (With Daclizumab Therapy)	Number of Participants Who Developed a Positive Antibody Response (IgG) to Keyhole Limpet Hemocyanin (KLH) Immunization	2 participants
Group B (Post Daclizumab Therapy)	Number of Participants Who Developed a Positive Antibody Response (IgG) to Keyhole Limpet Hemocyanin (KLH) Immunization	2 participants

Secondary

Geometric Mean Antibody Concentrations for KLH (IgM and IgG) and TT (IgG)

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

Secondary

Mean Percent Expression of 2A3/CD25+ Antibody

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

Population: 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	Measure	Group	Value (MEAN)	Dispersion
Group A (With Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Screening, n=1, 5	0.10 Percent expression	—
Group A (With Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Day 29, n=5, 3	0.12 Percent expression	Standard Deviation 0.084
Group A (With Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Day 57, n=5, 5	0.06 Percent expression	Standard Deviation 0.055
Group A (With Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Day 168, n=6, 3	8.33 Percent expression	Standard Deviation 2.67
Group B (Post Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Day 168, n=6, 3	12.53 Percent expression	Standard Deviation 4.888
Group B (Post Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Screening, n=1, 5	9.44 Percent expression	Standard Deviation 3.023
Group B (Post Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Day 57, n=5, 5	10.18 Percent expression	Standard Deviation 2.479
Group B (Post Daclizumab Therapy)	Mean Percent Expression of 2A3/CD25+ Antibody	Day 29, n=5, 3	8.53 Percent expression	Standard Deviation 2.003

Secondary

Mean Percent Expression of CD3, CD4, and CD8

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 57, n=5, 2	77.80 Percent expression	Standard Deviation 8.46
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 43, n=5, 2	47.08 Percent expression	Standard Deviation 8.685
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 22, n=6, 2	78.70 Percent expression	Standard Deviation 7.211
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 57, n=5, 2	47.58 Percent expression	Standard Deviation 8.404
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 1, n=6, 2	48.87 Percent expression	Standard Deviation 7.153
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 1, n=6, 2	24.07 Percent expression	Standard Deviation 5.452
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 43, n=5, 2	76.74 Percent expression	Standard Deviation 10.126
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 22, n=6, 2	25.15 Percent expression	Standard Deviation 6.806
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 22, n=6, 2	48.98 Percent expression	Standard Deviation 7.743
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 29, n=5, 2	24.06 Percent expression	Standard Deviation 7.79
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 29, n=5, 2	79.82 Percent expression	Standard Deviation 9.116
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 43, n=5, 2	24.00 Percent expression	Standard Deviation 8.405
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 29, n=5, 2	51.16 Percent expression	Standard Deviation 8.83
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 57, n=5, 2	24.86 Percent expression	Standard Deviation 7.11
Group A (With Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 1, n=6, 2	76.97 Percent expression	Standard Deviation 4.069
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 57, n=5, 2	38.55 Percent expression	Standard Deviation 11.243
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 1, n=6, 2	79.50 Percent expression	Standard Deviation 1.414
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 22, n=6, 2	77.25 Percent expression	Standard Deviation 1.202
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 29, n=5, 2	78.80 Percent expression	Standard Deviation 1.131
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 43, n=5, 2	78.65 Percent expression	Standard Deviation 0.778
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD3+, Day 57, n=5, 2	79.20 Percent expression	Standard Deviation 3.96
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 1, n=6, 2	36.90 Percent expression	Standard Deviation 7.212
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 22, n=6, 2	34.20 Percent expression	Standard Deviation 9.051
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 29, n=5, 2	34.85 Percent expression	Standard Deviation 7.566
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 43, n=5, 2	34.75 Percent expression	Standard Deviation 6.435
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD4+, Day 57, n=5, 2	36.85 Percent expression	Standard Deviation 6.718
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 1, n=6, 2	37.30 Percent expression	Standard Deviation 9.758
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 22, n=6, 2	38.25 Percent expression	Standard Deviation 11.526
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 29, n=5, 2	38.75 Percent expression	Standard Deviation 10.394
Group B (Post Daclizumab Therapy)	Mean Percent Expression of CD3, CD4, and CD8	CD8+, Day 43, n=5, 2	39.00 Percent expression	Standard Deviation 8.768

Secondary

Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+

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

Population: 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	Measure	Group	Value (MEAN)	Dispersion
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RA +, Day 1, n=6, 2	69.85 Percent expression	Standard Deviation 4.359
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	HLADR+, Day 1, n=6, 2	2.58 Percent expression	Standard Deviation 1.098
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	HLADR +, Day 29, n=5, 2	5.04 Percent expression	Standard Deviation 7.72
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	HLADR +, Day 57, n=5, 2	4.16 Percent expression	Standard Deviation 5.126
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RO +, Day 1, n=6, 2	22.85 Percent expression	Standard Deviation 3.69
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RO +, Day 29, n=5, 2	27.04 Percent expression	Standard Deviation 4.779
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RO +, Day 57, n=5, 2	26.90 Percent expression	Standard Deviation 7.027
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RA +, Day 29, n=5, 2	66.86 Percent expression	Standard Deviation 5.663
Group A (With Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RA +, Day 57, n=5, 2	62.84 Percent expression	Standard Deviation 5.999
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RA +, Day 57, n=5, 2	56.15 Percent expression	Standard Deviation 5.869
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RO +, Day 29, n=5, 2	39.45 Percent expression	Standard Deviation 8.556
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	HLADR+, Day 1, n=6, 2	5.80 Percent expression	Standard Deviation 3.394
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RA +, Day 29, n=5, 2	52.70 Percent expression	Standard Deviation 10.041
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	HLADR +, Day 29, n=5, 2	5.10 Percent expression	Standard Deviation 4.101
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RO +, Day 57, n=5, 2	34.45 Percent expression	Standard Deviation 3.323
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	HLADR +, Day 57, n=5, 2	4.55 Percent expression	Standard Deviation 3.182
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RA +, Day 1, n=6, 2	50.50 Percent expression	Standard Deviation 4.384
Group B (Post Daclizumab Therapy)	Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+	CD45RO +, Day 1, n=6, 2	39.45 Percent expression	Standard Deviation 3.889

Secondary

Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response

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

Population: 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	Measure	Value (NUMBER)
Group A (With Daclizumab Therapy)	Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response	1 participants
Group B (Post Daclizumab Therapy)	Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response	1 participants

Secondary

Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization

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

Arm	Measure	Value (NUMBER)
Group A (With Daclizumab Therapy)	Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization	0 participants
Group B (Post Daclizumab Therapy)	Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization	0 participants

Secondary

Number of Participants Who Developed a Positive Antibody Response to KLH and Positive Cellular Responses to Both KLH and TT Immunizations

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