Renal TransplantationPhase 3NCT02686619
Study Comparing Efficacy and Safety of Mycophenolate Mofetil (Cellcept) With Delayed Introduction of Sirolimus and Discontinuation of Cyclosporine, With Those of Mycophenolate Mofetil and Long Term Continuation of Cyclosporine in Renal Transplant Recipients
A Phase 3 study testing Cyclosporine, Daclizumab and Mycophenoate Mofetil in people with Renal Transplantation, run by Hoffmann-La Roche at 17 sites in France.
Trial summary
This multicentre, prospective, randomized, open-label study will compare the safety and efficacy of mycophenolate mofetil with delayed introduction of sirolimus and discontinuation of cyclosporine, with those of mycophenolate mofetil and long term continuation of cyclosporine in renal transplant recipients receiving… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- Cyclosporine, Daclizumab and Mycophenoate Mofetil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 237 participants
- Where
- 17 sitesFrance
- Study dates
- Nov 2004to Jan 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Receipt of a first cadaveric kidney graft
- Antilymphocyte antibodies and panel reactive antibodies (PRA) less than 30 percent (%) (historical peak and/or current value)
- Cold ischaemia time less than or equal to 36 hours
Who cannot join
- Kidney from a living donor; donor greater than (>) 65 years of age; second renal graft, or more; or multiple organ transplant
- Known hypersensitivity to any of the drugs in the study or their components
- History of cancer or malignancy during previous 5 years, other than successfully treated spinocellular or basal cell cancer
- Participant presenting, on inclusion, either symptoms suggestive of active gastroduodenal ulcer, or gastroduodenal ulcer confirmed by fibroscopy and biopsy, and requiring treatment
- Participant with severe refractory hyperlipidaemia
- Pregnant woman or nursing mother
Show all 10Show fewer
- Episode of acute rejection greater than or equal to grade I (Banff classification)
- Estimated creatinine clearance (CrCl) at week 12 less than (<) 40 milliliter per minute (mL/min) (Cockcroft-Gault formula)
- Serum creatinine variations >30% during the 15 days before randomization
- Proteinuria >1 gram/24 hour, or mean mycophenolate mofetil dose < 1.5 gram/day during the week before randomization
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
Study site
Angers, 49933
Study site
Caen, 14033
Study site
Clermont-Ferrand, 63000
Study site
La Tronche, 38700
Study site
Lille, 59037
Study site
Limoges, 87042
Study site
Lyon, 69437
Study site
Paris, 75018
Study site
Paris, 75475
Study site
Paris, 75743
Study site
Poitiers, 86021
Study site
Reims, 51092
Study site
Rennes, 35033
Study site
Rouen, 76031
Study site
Salouël, 80480
Study site
Strasbourg, 67091
Study site
Tours, 37044
About this study
Official title: Multicentre, Prospective, Randomized, Open-label Study Comparing the Efficacy and Safety of CellCept With Delayed Introduction of Sirolimus and Discontinuation of Cyclosporine, With Those of Standard Immunosuppression Comprising CellCept and Long-term Continuation of Cyclosporine in Renal Transplant Recipients Receiving Induction by Zenapax and Treated With Corticosteroids for 8 Months
This multicentre, prospective, randomized, open-label study will compare the safety and efficacy of mycophenolate mofetil with delayed introduction of sirolimus and discontinuation of cyclosporine, with those of mycophenolate mofetil and long term continuation of cyclosporine in renal transplant recipients receiving daclizumab (Zenapax) as induction treatment and followed by 8 month treatment with corticosteroids. The anticipated time on study treatment is 12 months. Participants who will complete the initial 12-month study and who will provide written informed consent will be eligible to participate in a 60-month follow-up phase.
- Conditions
- Renal Transplantation
- Being tested
- Cyclosporine, Daclizumab, Mycophenoate Mofetil, Prednisolone, Sirolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporineDrug
Also called Neoral
Cyclosporine tablets orally once daily at dose level adapted to maintain concentration at 2 hours after administration (C2): 1000-1500 nanogram per milliliter (ng/mL) during Day 0 to Week 4, and 800-1200 ng/mL during Week 4 to Week 52. For Mycophenoate Mofetil + Sirolimus treatment arm, at Week 12, dose of cyclosporine will be reduced by 50% for 3 days, followed by 1/4 of the dose for 3 days, and then cyclosporine will be stopped.
DaclizumabDrug
Also called Zenapax
Daclizumab 2 milligram (mg) per kilogram (kg) will be administered as intravenous infusion over 15 minute on Day 0 (during the 24 hours preceding renal transplantation) and at a dose of 1 mg/kg on Day14.
Mycophenoate MofetilDrug
Also called CellCept
Mycophenoate mofetil 1 gram (g) (2*500mg tablets or 4*250mg capsules) will be given twice daily (daily dose of 2 g) orally for 12 months.
PrednisoloneDrug
Also called Solupred
Prednisolone 250 mg intravenously on Day 0, followed by 0.5 mg/kg orally daily (maximum 40 mg daily) from Day 1 to Day 7, then 0.25 mg/kg orally daily (maximum 20 mg daily), then dose will be stepwise reduced by 2.5 mg per week to reach to a dose level of 10 mg daily and continued up to 6 months and finally drug will be discontinued after 8 months.
SirolimusDrug
Also called Rapamycin
Sirolimus tablets will be given orally from week 12 to week 52, starting with loading dose of 10 mg daily for 2 days followed by 6 mg daily to adapt to trough concentrations of 8-15 ng/mL from week 12 to week 39, and 5-10 ng/mL from week 39 to week 52.
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate Mofetil + Cyclosporine | Active comparator | Participants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. Receives: Drug: Cyclosporine; Drug: Daclizumab; Drug: Mycophenoate Mofetil; Drug: Prednisolone |
| Mycophenolate Mofetil + Sirolimus | Experimental | Participants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. Receives: Drug: Cyclosporine; Drug: Daclizumab; Drug: Mycophenoate Mofetil; Drug: Prednisolone; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60
Measured: 60 months
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Up to approximately 12 months
Number of Participants With Serious Adverse Events (SAEs)
Measured: From 12 months up to 60 months
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Week 52
Measured: 52 weeks
Number of Participants With Cancers and Lymphoproliferative Syndromes
Measured: Up to approximately 12 months
Number of Participants With Premature Discontinuations due to Adverse Events (AEs)
Measured: Up to approximately 12 months
Change From Baseline in 24-Hour Urinary Protein at Week 52
Measured: 52 weeks
Secondary outcomes (10)
Mean Inverse Creatinine Concentration
Measured: Week 4, 8, 12, 14, 16, 26, 39, and 52
Creatinine Clearance Calculated and Corrected According to Cockcroft-Gault
Measured: Week 4, 8, 12, 14, 16, 26, 39, and 52
Glomerular Filtration Rate (GFR) Measured by Iohexol Clearance
Measured: Baseline, Week 52
Number of Participants with Response to Treatment, Defined as Creatinine Clearance >/=60 mL/min at Week 52
Measured: Week 52
Number of Participants With Treated Rejections
Measured: Baseline up to Week 52
Mean Serum Creatinine Concentration
Measured: Week 4, 8, 12, 14, 16, 26, 39, and 52
Number of Participants With Biopsy-proven Acute Rejections
Measured: Baseline up to Month 60
Number of Participants With Histologic Evaluation of the Graft
Measured: Week 52
Number of Participants Who Were Alive
Measured: Month 60
Number of Participants With Graft Survival
Measured: Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study startNov 2004
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 237 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
- NCT02686619
- Sponsor's protocol ID
- ML18326
- Status last verified
- Feb 2016
- First submitted
- 16 Feb 2016
- Last updated
- 19 Feb 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Prospective, Randomized, Open-label Study Comparing the Efficacy and Safety of CellCept With Delayed Introduction of Sirolimus and Discontinuation of Cyclosporine, With Those of Standard Immunosuppression Comprising CellCept and Long-term Continuation of Cyclosporine in Renal Transplant Recipients Receiving Induction by Zenapax and Treated With Corticosteroids for 8 Months
- ClinicalTrials.gov ID
- NCT02686619
- Acronym / sponsor ID
- ML18326
- Conditions
- Renal Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 237 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Nov 2004
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 19 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicentre, prospective, randomized, open-label study will compare the safety and efficacy of mycophenolate mofetil with delayed introduction of sirolimus and discontinuation of cyclosporine, with those of mycophenolate mofetil and long term continuation of cyclosporine in renal transplant recipients receiving daclizumab (Zenapax) as induction treatment and followed by 8 month treatment with corticosteroids. The anticipated time on study treatment is 12 months. Participants who will complete the initial 12-month study and who will provide written informed consent will be eligible to participate in a 60-month follow-up phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate Mofetil + Cyclosporine | Active comparator | Drug: Cyclosporine, Drug: Daclizumab, Drug: Mycophenoate Mofetil, Drug: PrednisoloneParticipants will receive mycophenoate mofetil, daclizumab, cyclosporine, and corticosteroids (prednisolone) for 3 to 12 months. |
| Mycophenolate Mofetil + Sirolimus | Experimental | Drug: Cyclosporine, Drug: Daclizumab, Drug: Mycophenoate Mofetil, Drug: Prednisolone, Drug: SirolimusParticipants will receive mycophenoate mofetil, daclizumab, and corticosteroids (prednisolone) for 3 to 12 months. Participants will also receive cyclosporine which will be replaced with sirolimus at later stage of the study. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Receipt of a first cadaveric kidney graft
- Antilymphocyte antibodies and panel reactive antibodies (PRA) less than 30 percent (%) (historical peak and/or current value)
- Cold ischaemia time less than or equal to 36 hours
Key exclusion criteria (10 listed)
- Kidney from a living donor; donor greater than (>) 65 years of age; second renal graft, or more; or multiple organ transplant
- Known hypersensitivity to any of the drugs in the study or their components
- History of cancer or malignancy during previous 5 years, other than successfully treated spinocellular or basal cell cancer
- Participant presenting, on inclusion, either symptoms suggestive of active gastroduodenal ulcer, or gastroduodenal ulcer confirmed by fibroscopy and biopsy, and requiring treatment
- Participant with severe refractory hyperlipidaemia
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 |
|---|---|---|
| CyclosporineAlso: NeoralCyclosporine tablets orally once daily at dose level adapted to maintain concentration at 2 hours after administration (C2): 1000-1500 nanogram per milliliter (ng/mL) during Day 0 to Week 4, and 800-1200 ng/mL during Week 4 to Week 52. For Mycophenoate Mofetil + Sirolimus treatment arm, at Week 12, dose of cyclosporine will be reduced by 50% for 3 days, followed by 1/4 of the dose for 3 days, and then cyclosporine will be stopped. | Drug | Mycophenolate Mofetil + Cyclosporine, Mycophenolate Mofetil + Sirolimus |
| DaclizumabAlso: ZenapaxDaclizumab 2 milligram (mg) per kilogram (kg) will be administered as intravenous infusion over 15 minute on Day 0 (during the 24 hours preceding renal transplantation) and at a dose of 1 mg/kg on Day14. | Drug | Mycophenolate Mofetil + Cyclosporine, Mycophenolate Mofetil + Sirolimus |
| Mycophenoate MofetilAlso: CellCeptMycophenoate mofetil 1 gram (g) (2*500mg tablets or 4*250mg capsules) will be given twice daily (daily dose of 2 g) orally for 12 months. | Drug | Mycophenolate Mofetil + Cyclosporine, Mycophenolate Mofetil + Sirolimus |
| PrednisoloneAlso: SolupredPrednisolone 250 mg intravenously on Day 0, followed by 0.5 mg/kg orally daily (maximum 40 mg daily) from Day 1 to Day 7, then 0.25 mg/kg orally daily (maximum 20 mg daily), then dose will be stepwise reduced by 2.5 mg per week to reach to a dose level of 10 mg daily and continued up to 6 months and finally drug will be discontinued after 8 months. | Drug | Mycophenolate Mofetil + Cyclosporine, Mycophenolate Mofetil + Sirolimus |
| SirolimusAlso: RapamycinSirolimus tablets will be given orally from week 12 to week 52, starting with loading dose of 10 mg daily for 2 days followed by 6 mg daily to adapt to trough concentrations of 8-15 ng/mL from week 12 to week 39, and 5-10 ng/mL from week 39 to week 52. | Drug | Mycophenolate Mofetil + Sirolimus |
Primary outcome
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60
Time frame: 60 months
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 12 months
Number of Participants With Serious Adverse Events (SAEs)
Time frame: From 12 months up to 60 months
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Week 52
Time frame: 52 weeks
Number of Participants With Cancers and Lymphoproliferative Syndromes
Time frame: Up to approximately 12 months
Number of Participants With Premature Discontinuations due to Adverse Events (AEs)
Time frame: Up to approximately 12 months
Change From Baseline in 24-Hour Urinary Protein at Week 52
Time frame: 52 weeks
10 secondary outcomes
Mean Inverse Creatinine Concentration
Time frame: Week 4, 8, 12, 14, 16, 26, 39, and 52
Creatinine Clearance Calculated and Corrected According to Cockcroft-Gault
Time frame: Week 4, 8, 12, 14, 16, 26, 39, and 52
Glomerular Filtration Rate (GFR) Measured by Iohexol Clearance
Time frame: Baseline, Week 52
Number of Participants with Response to Treatment, Defined as Creatinine Clearance >/=60 mL/min at Week 52
Time frame: Week 52
Number of Participants With Treated Rejections
Time frame: Baseline up to Week 52
Mean Serum Creatinine Concentration
Time frame: Week 4, 8, 12, 14, 16, 26, 39, and 52
Number of Participants With Biopsy-proven Acute Rejections
Time frame: Baseline up to Month 60
Number of Participants With Histologic Evaluation of the Graft
Time frame: Week 52
Number of Participants Who Were Alive
Time frame: Month 60
Number of Participants With Graft Survival
Time frame: Month 60
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2016.
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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
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclosporine, Daclizumab and Mycophenoate Mofetil in people with Renal Transplantation, run by Hoffmann-La Roche at 17 sites in France.
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 3 inclusion and 10 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 19 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Creatinine Clearance Calculated and Corrected According to Cockcroft Gault at Month 60 (time frame: 60 months). The study lists 7 primary outcomes in all. 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 19 Feb 2016.