Kidney TransplantationPhase 4NCT02576145
A Study to Assess Immune Response in Pediatric Kidney Transplant Recipients Treated With Daclizumab (Zenapax)
A Phase 4 study testing DT, Daclizumab and KLH in people with Kidney Transplantation, run by Hoffmann-La Roche at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 19 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- DT, Daclizumab and KLH
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 5 sitesUnited States
- Study dates
- Apr 2003to Jan 2006
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Study site
Indianapolis, Indiana, 46202
Study site
Kansas City, Missouri, 64108
Study site
Los Angeles, California, 90027-6062
Study site
Los Angeles, California, 90095-1752
Study site
Portland, Oregon, 97201
About this study
Official title: 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.
- Conditions
- Kidney Transplantation
- Being tested
- DT, Daclizumab, KLH
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTBiological
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.
DaclizumabDrug
Also called Zenapax
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).
KLHBiological
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 group | Role | What they receive |
|---|---|---|
| Group A (With Daclizumab Therapy) | Experimental | 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. Receives: Biological: DT; Drug: Daclizumab; Biological: KLH |
| Group B (Post Daclizumab Therapy) | Active comparator | Participants who completed a full course of daclizumab therapy in the previous 4 to 18 months. Receives: Biological: DT; Biological: KLH |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Developed a Positive Antibody Response (IgG) to Keyhole Limpet Hemocyanin (KLH) Immunization
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).
Measured: Baseline and Day 43 or Day 57
Secondary outcomes (15)
Number of Participants Who Developed a Positive Cellular Response to KLH Immunization
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.
Measured: 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
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.
Measured: Baseline, Day 22, Day 29, Day 43 and Day 57
Number of Participants Who Developed a Positive Humoral Response to Tetanus Toxoid (TT)
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.
Measured: Baseline, Day 22, Day 29, Day 43 and Day 57
Number of Participants Who Developed a Positive Cellular Response to Tetanus Toxoid (TT)
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.
Measured: 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
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.
Measured: 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
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.
Measured: Up to Day 252
Number of Tetanus Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Tetanus Response
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.
Measured: up to Day 252
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.
Measured: Screening, Day 22, Day 29, Day 43 and Day 57
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.
Measured: Screening, Day 29, Day 57 and Day 168
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.
Measured: Days 1, 22, 29, 43 and 57
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.
Measured: Days 1, 29 and 57
Percentage of Participants With Positive Antibody Response to KLH Immunization at 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.
Measured: Month 6
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).
Measured: Up to Day 252
Number of Participants With a Positive Delayed Type Hypersensitivity (DTH) Response After KLH Immunization
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.
Measured: Day 1 and Day 29
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
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
Measured: Up to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study startApr 2003
- Primary completionJan 2006
- Study completionJan 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02576145
- Sponsor's protocol ID
- PA16215
- Status last verified
- Dec 2015
- First submitted
- 5 Oct 2015
- Last updated
- 13 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Response to Neoantigen and Recall Antigen in Pediatric Renal Transplant Recipients Treated With the IL-2R Alfa Monoclonal Antibody, Daclizumab (Zenapax®)
- ClinicalTrials.gov ID
- NCT02576145
- Acronym / sponsor ID
- PA16215
- Conditions
- Kidney Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Apr 2003
- Primary completion
- Jan 2006 (actual)
- Study completion
- Jan 2006 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Posted 13 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (With Daclizumab Therapy) | Experimental | Biological: DT, Drug: Daclizumab, Biological: KLHParticipants 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. |
| Group B (Post Daclizumab Therapy) | Active comparator | Biological: DT, Biological: KLHParticipants who completed a full course of daclizumab therapy in the previous 4 to 18 months. |
Who may qualify
- Ages
- 2 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DTDiphtheria 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 | Group A (With Daclizumab Therapy), Group B (Post Daclizumab Therapy) |
| DaclizumabAlso: ZenapaxThe 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). | Drug | Group A (With Daclizumab Therapy) |
| KLHKLH 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. | Biological | Group A (With Daclizumab Therapy), Group B (Post Daclizumab Therapy) |
Primary outcome
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).
15 secondary outcomes
Number of Participants Who Developed a Positive Cellular Response to KLH Immunization
Time frame: 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
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
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
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
Number of KLH Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Response to KLH Immunization
Time frame: Up to Day 252
Number of Tetanus Cellular Nonresponders Who Were Rechallenged and Mounted a Cellular Tetanus Response
Time frame: 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
Mean Percent Expression of 2A3/CD25+ Antibody
Time frame: 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
Mean Percent Expression of HLA-DR+, CD45RO+ and CD45RA+
Time frame: Days 1, 29 and 57
Percentage of Participants With Positive Antibody Response to KLH Immunization at Month 6
Time frame: Month 6
Number of KLH Antibody Nonresponders Who Underwent Rechallenge and Mounted a KLH Antibody Response
Time frame: 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
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Time frame: Up to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study chair
Hoffmann-La Roche
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing DT, Daclizumab and KLH in people with Kidney Transplantation, run by Hoffmann-La Roche at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2016.