- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02576145
A Study to Assess Immune Response in Pediatric Kidney Transplant Recipients Treated With Daclizumab (Zenapax)
December 9, 2015 updated by: Hoffmann-La Roche
Immune Response to Neoantigen and Recall Antigen in Pediatric Renal Transplant Recipients Treated With the IL-2R Alfa Monoclonal Antibody, Daclizumab (Zenapax®)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
11
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Los Angeles, California, United States, 90027-6062
-
Los Angeles, California, United States, 90095-1752
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
-
-
Missouri
-
Kansas City, Missouri, United States, 64108
-
-
Oregon
-
Portland, Oregon, United States, 97201
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 19 years (ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / 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.
|
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.
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:
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.
|
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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).
|
Baseline and Day 43 or Day 57
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Developed a Positive Cellular Response to KLH Immunization
Time Frame: 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.
|
Baseline, Day 22, Day 29, Day 43, and Day 57
|
Number of Participants Who Developed Both a Positive Antibody Response and a Positive Cellular Response to KLH Immunization
Time Frame: 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.
|
Baseline, Day 22, Day 29, Day 43 and Day 57
|
Number of Participants Who Developed a Positive Humoral Response to Tetanus Toxoid (TT)
Time Frame: 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.
|
Baseline, Day 22, Day 29, Day 43 and Day 57
|
Number of Participants Who Developed a Positive Cellular Response to Tetanus Toxoid (TT)
Time Frame: 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.
|
Baseline, Day 22, Day 29, Day 43 and Day 57
|
Number of Participants Who Developed a Positive Antibody Response to KLH and Positive Cellular Responses to Both KLH and TT Immunizations
Time Frame: 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.
|
Baseline, Day 22, Day 29, Day 43 and Day 57
|
Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization
Time Frame: 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.
|
Up to Day 252
|
Number of Tetanus Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Tetanus Response
Time Frame: 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.
|
up to Day 252
|
Geometric Mean Antibody Concentrations for KLH (IgM and IgG) and TT (IgG)
Time Frame: 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.
|
Screening, Day 22, Day 29, Day 43 and Day 57
|
Mean Percent Expression of 2A3/CD25+ Antibody
Time Frame: 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.
|
Screening, Day 29, Day 57 and Day 168
|
Mean Percent Expression of CD3, CD4, and CD8
Time Frame: 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.
|
Days 1, 22, 29, 43 and 57
|
Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+
Time Frame: 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.
|
Days 1, 29 and 57
|
Percentage of Participants With Positive Antibody Response to KLH Immunization at Month 6
Time Frame: 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.
|
Month 6
|
Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response
Time Frame: 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).
|
Up to Day 252
|
Number of Participants With a Positive Delayed Type Hypersensitivity (DTH) Response After KLH Immunization
Time Frame: 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.
|
Day 1 and Day 29
|
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Time Frame: 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
|
Up to Month 12
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2003
Primary Completion (Actual)
January 1, 2006
Study Completion (Actual)
January 1, 2006
Study Registration Dates
First Submitted
October 5, 2015
First Submitted That Met QC Criteria
October 12, 2015
First Posted (Estimate)
October 15, 2015
Study Record Updates
Last Update Posted (Estimate)
January 13, 2016
Last Update Submitted That Met QC Criteria
December 9, 2015
Last Verified
December 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PA16215
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Kidney Transplantation
-
Astellas Pharma IncAstellas Pharma Europe B.V.CompletedKidney Transplantation | Renal Transplantation | Transplantation, Kidney | Grafting, Kidney | Transplantation, RenalBelgium, Germany, Spain, Sweden, Italy, Switzerland, United Kingdom, Austria, France, Poland, Czech Republic, Netherlands
-
Bristol-Myers SquibbCompletedKidney Transplantation: Transplantation, Kidney
-
Nantes University HospitalTerminated
-
Hospices Civils de LyonCompletedKidney Transplantation | Pancreas-kidney TransplantationFrance
-
Astellas Pharma Europe Ltd.CompletedLiver Transplantation | Kidney Transplantation | Heart TransplantationCzechia, France, Italy, Poland, United Kingdom
-
The Hospital for Sick ChildrenCompletedLiver Transplantation | Kidney Transplantation | Heart TransplantationCanada
-
Astellas Pharma Europe Ltd.TerminatedLiver Transplantation | Kidney Transplantation | Heart TransplantationBelgium, France, Germany, Poland, Spain, United Kingdom
-
Astellas Pharma Europe Ltd.CompletedLiver Transplantation | Kidney Transplantation | Heart TransplantationSpain, Australia, France, Germany, Canada, Italy, United Kingdom, Belgium, South Africa, Switzerland, Sweden, United States, Austria, Brazil, Czechia, Denmark, Finland, Hungary, Ireland, Mexico, Netherlands, New Zealand, Poland
-
Astellas Pharma Europe Ltd.CompletedLiver Transplantation | Kidney Transplantation | Heart TransplantationBelgium, France, Germany, Poland, Spain, United Kingdom
-
Medical University of ViennaUnknownKidney Function After Transplantation | Outcome After Kidney Transplantation
Clinical Trials on DT
-
Design TherapeuticsCompleted
-
Design Therapeutics, Inc.CompletedFriedreich AtaxiaUnited States
-
Sunnaas Rehabilitation HospitalNorwegian University of Science and TechnologyRecruitingStroke | Brain Injuries | Acquired Brain Injury | TBINorway
-
Chulalongkorn UniversityRecruitingPediatric HIV InfectionThailand
-
University of Colorado, DenverPatient-Centered Outcomes Research InstituteCompletedHeart Failure | Heart-assist DevicesUnited States
-
Zogenix MDS, Inc.CompletedThymidine Kinase 2 (TK2)United States, Spain, Israel
-
Domain Therapeutics SARecruitingSolid Tumor, AdultFrance, Belgium
-
Medtronic Bakken Research CenterMedtronicCompleted
-
US Department of Veterans AffairsCompletedDiabetes Mellitus | Ulcer | Diabetic PolyneuropathyUnited States
-
Consolidated Research, Inc.Recruiting