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

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ClinicalTrials.gov Identifier: NCT02576145
Recruitment Status : Completed
First Posted : October 15, 2015
Results First Posted : January 13, 2016
Last Update Posted : January 13, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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 Type : Interventional  (Clinical Trial)
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 : April 2003
Actual Primary Completion Date : January 2006
Actual Study Completion Date : January 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Daclizumab

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 Name: 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.




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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).

  14. 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.

  15. 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



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Ages Eligible for Study:   2 Years to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02576145


Locations
United States, California
Los Angeles, California, United States, 90027-6062
Los Angeles, California, United States, 90095-1752
United States, Indiana
Indianapolis, Indiana, United States, 46202
United States, Missouri
Kansas City, Missouri, United States, 64108
United States, Oregon
Portland, Oregon, United States, 97201
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02576145     History of Changes
Other Study ID Numbers: PA16215
First Posted: October 15, 2015    Key Record Dates
Results First Posted: January 13, 2016
Last Update Posted: January 13, 2016
Last Verified: December 2015

Additional relevant MeSH terms:
Daclizumab
Immunoglobulin G
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs