Kidney TransplantationPhase 3NCT02005562
OPERA Study: A Study of Two Dosing Regimens of CellCept (Mycophenolate Mofetil) in Kidney Transplant Patients.
A Phase 3 study testing mycophenolate mofetil, anti-IL-2R and methylprednisolone in people with Kidney Transplantation, run by Hoffmann-La Roche at 24 sites in France.
Trial summary
This study will compare the incidence of acute clinical or subclinical rejection between immunosuppression with CellCept at a starting dose of 3mg po daily with therapeutic drug monitoring and standard immunosuppression with CellCept and a fixed dose of 2g po daily, in kidney transplant recipients receiving induction… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- mycophenolate mofetil, anti-IL-2R and methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 252 participants
- Where
- 24 sitesFrance
- Study dates
- May 2006to Mar 2009
- Phase
- Phase 3
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients, aged 18-75 years of age;
- in receipt of first donor kidney;
- eligible to receive immunosuppressive treatment comprising IRL2, CellCept, cyclosporine and steroids;
- eligible to receive oral treatment from the first day post-transplantation.
Who cannot join
- patients receiving a second or subsequent kidney transplant, or multi-organ transplant;
- history of malignancy in the last 5 years (except successfully treated squamous cell or basal cell cancer and cervical cancer in situ);
- patients with active hepatitis B and/or hepatitis C, or HIV infection.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
France24 sites
Study site
Bordeaux, 33076
Study site
Brest, 29609
Study site
Clermont-Ferrand, 63000
Study site
Créteil, 94010
Study site
Dijon, 21079
Study site
La Tronche, 38700
Study site
Le Kremlin-Bicêtre, 94275
Study site
Lille, 59037
Study site
Limoges, 87042
Study site
Montpellier, 34295
Study site
Nantes, 44035
Study site
Nice, 06002
Study site
Paris, 75018
Study site
Paris, 75475
Study site
Paris, 75743
Study site
Paris, 75970
Study site
Poitiers, 86021
Study site
Rennes, 35033
Study site
Salouël, 80480
Study site
Strasbourg, 67091
Study site
Suresnes, 92151
Study site
Toulouse, 31054
Study site
Tours, 37044
Study site
Vandœuvre-lès-Nancy, 54511
About this study
Official title: A Randomized Study Comparing the Incidence of Acute Clinical or Subclinical Rejection With Two Dosing Regimens of CellCept in de Novo Renal Transplant Recipients Receiving Induction, Cyclosporine and Brief Steroid Therapy
This study will compare the incidence of acute clinical or subclinical rejection between immunosuppression with CellCept at a starting dose of 3mg po daily with therapeutic drug monitoring and standard immunosuppression with CellCept and a fixed dose of 2g po daily, in kidney transplant recipients receiving induction by anti-IRL2, cyclosporine therapy, and early discontinuation of steroids. Patients will be randomized to one of the two treatment arms. The anticipated time on study treatment is 52 weeks.
- Conditions
- Kidney Transplantation
- Being tested
- mycophenolate mofetil, anti-IL-2R, methylprednisolone, cyclosporine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called CellCept
3 g p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing to Week 52, adapted to MPA by AUC on Weeks 2, 6, 12, 26, and 52 to obtain AUC0-12 of 50 milligrams (mg) multiplied by (*) height (h)/ liter(L).
Also called CellCept
2 g p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing to Week 52.
anti-IL-2RDrug
Induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion.
Also called Solumedrol
500 mg intravenous (i.v.) was administered before or after the transplantation, and 0.5 mg/kg p.o. daily from Day 1 to Day 7.
cyclosporineDrug
100-1500 nanograms (ng) per milliliter (mL) from Day 0 to Week 4, 800-1200 ng/mL from Week 4 to Week 12 and 500-800 ng/mL from Week 12 to Week 52
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Experimental | Participants received 3 grams (g) mycophenolate mofetil (MMF) tablets per os (p.o.) in divided doses (every 12 hours [q12h]) adapted to mycophenolic acid (MPA) by area under the curve (AUC) beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by interleukin-2R (IL-2R) was administered at Day 0 per standard of care at the site at the investigator's discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 nanograms (ng) per (/) milliliter (mL) from Day 0 to (-) Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg intravenously (i.v.) was administered before or after the transplantation, and 0.5 milligrams (mg) per kilogram (kg) p.o. daily from Day 1 - Day 7. Receives: Drug: mycophenolate mofetil; Drug: anti-IL-2R; Drug: methylprednisolone; Drug: cyclosporine |
| Mycophenolate Mofetil, Fixed Dose | Active comparator | Participants received 2 g MMF tablets p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 ng/mL from Day 0 - Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg i.v. was administered before or after the transplantation, and 0.5 mg/kg p.o. daily from Day 1 - Day 7. Receives: Drug: mycophenolate mofetil; Drug: anti-IL-2R; Drug: methylprednisolone; Drug: cyclosporine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10 percent (%) compared to baseline (BL) values and BPAR of Grade greater than or equal to (≥) 1 according to Banff 1997 classification at Week 12.
Measured: Week 12
Secondary outcomes (11)
Serum Creatinine Values [Micromoles Per Liter (µmol/L)]
The mean serum creatinine values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52.
Measured: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min])
The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the Cockcroft-Gault equation.
Measured: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation
The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the MDRD simplified equation. For males, the MDRD simplified equation was defined as MDRD (mL/min/1.73 square meters [m^2]) =186 multiplied by (*) serum creatinine in mg/L raised to the power of (^) -1.154 * age ^ -0.203. For females, the MDRD simplified equation was defined as MDRD (mL/min/1.73 m^2) = males formula * 0.742.
Measured: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection at Week 12 was included in the analysis. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10% compared to BL values and BPAR of Grade ≥1 according to Banff 1997 classification at Week 12. The occurrence of the first BPAR was defined as the time from randomization to the first recorded BPAR between Day 0 and Week 52. The results of protocol biopsies at Week 12 were taken into account. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Time to Occurrence of First BPAR Between Day 0 and Week 52
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection at Week 12 was included in the analysis. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10% compared to BL values and BPAR of Grade ≥1 according to Banff 1997 classification at Week 12. The occurrence of the first BPAR was defined as the time from randomization to the first recorded BPAR between Day 0 and Week 52. The results of protocol biopsies at Week 12 were taken into account. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Percentage of Participants With at Least One BPAR at Week 12 and Week 52
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Weeks 12 and 52
Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52
Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Weeks 12 and 52
Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52
Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Weeks 12 and 52
Graft Loss - Percentage of Participants With an Event
Graft loss was defined as physical loss (nephrectomy), functional loss [necessitating maintenance dialysis for greater than (>)8 weeks], retransplant or death. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Time to Graft Loss
The median time, in days, from randomization to graft loss event. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Participant Survival
Participants survival was defined as the percentage of participants living with or without a functioning graft between Weeks 0 and 52. Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.
Measured: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2013 (estimated)
- Study startMay 2006
- Primary completionMar 2009
- Study completionMar 2009
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 252 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
- NCT02005562
- Sponsor's protocol ID
- ML19912
- Status last verified
- Oct 2015
- First submitted
- 4 Dec 2013
- Last updated
- 11 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study Comparing the Incidence of Acute Clinical or Subclinical Rejection With Two Dosing Regimens of CellCept in de Novo Renal Transplant Recipients Receiving Induction, Cyclosporine and Brief Steroid Therapy
- ClinicalTrials.gov ID
- NCT02005562
- Acronym / sponsor ID
- ML19912
- Conditions
- Kidney Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 9 Dec 2013 (estimated)
- Results
- Posted 11 Nov 2015
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 compare the incidence of acute clinical or subclinical rejection between immunosuppression with CellCept at a starting dose of 3mg po daily with therapeutic drug monitoring and standard immunosuppression with CellCept and a fixed dose of 2g po daily, in kidney transplant recipients receiving induction by anti-IRL2, cyclosporine therapy, and early discontinuation of steroids. Patients will be randomized to one of the two treatment arms. The anticipated time on study treatment is 52 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate Mofetil, Adapted Dose | Experimental | Drug: mycophenolate mofetil, Drug: anti-IL-2R, Drug: methylprednisolone, Drug: cyclosporineParticipants received 3 grams (g) mycophenolate mofetil (MMF) tablets per os (p.o.) in divided doses (every 12 hours [q12h]) adapted to mycophenolic acid (MPA) by area under the curve (AUC) beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by interleukin-2R (IL-2R) was administered at Day 0 per standard of care at the site at the investigator's discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 nanograms (ng) per (/) milliliter (mL) from Day 0 to (-) Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg intravenously (i.v.) was administered before or after the transplantation, and 0.5 milligrams (mg) per kilogram (kg) p.o. daily from Day 1 - Day 7. |
| Mycophenolate Mofetil, Fixed Dose | Active comparator | Drug: mycophenolate mofetil, Drug: anti-IL-2R, Drug: methylprednisolone, Drug: cyclosporineParticipants received 2 g MMF tablets p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 ng/mL from Day 0 - Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg i.v. was administered before or after the transplantation, and 0.5 mg/kg p.o. daily from Day 1 - Day 7. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- adult patients, aged 18-75 years of age;
- in receipt of first donor kidney;
- eligible to receive immunosuppressive treatment comprising IRL2, CellCept, cyclosporine and steroids;
- eligible to receive oral treatment from the first day post-transplantation.
Key exclusion criteria (3 listed)
- patients receiving a second or subsequent kidney transplant, or multi-organ transplant;
- history of malignancy in the last 5 years (except successfully treated squamous cell or basal cell cancer and cervical cancer in situ);
- patients with active hepatitis B and/or hepatitis C, or HIV infection.
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 |
|---|---|---|
| mycophenolate mofetilAlso: CellCept3 g p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing to Week 52, adapted to MPA by AUC on Weeks 2, 6, 12, 26, and 52 to obtain AUC0-12 of 50 milligrams (mg) multiplied by (*) height (h)/ liter(L). | Drug | Mycophenolate Mofetil, Adapted Dose |
| mycophenolate mofetilAlso: CellCept2 g p.o. in divided doses q12h beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing to Week 52. | Drug | Mycophenolate Mofetil, Fixed Dose |
| anti-IL-2RInduction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion. | Drug | Mycophenolate Mofetil, Adapted Dose, Mycophenolate Mofetil, Fixed Dose |
| methylprednisoloneAlso: Solumedrol500 mg intravenous (i.v.) was administered before or after the transplantation, and 0.5 mg/kg p.o. daily from Day 1 to Day 7. | Drug | Mycophenolate Mofetil, Adapted Dose, Mycophenolate Mofetil, Fixed Dose |
| cyclosporine100-1500 nanograms (ng) per milliliter (mL) from Day 0 to Week 4, 800-1200 ng/mL from Week 4 to Week 12 and 500-800 ng/mL from Week 12 to Week 52 | Drug | Mycophenolate Mofetil, Adapted Dose, Mycophenolate Mofetil, Fixed Dose |
Primary outcome
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12
Time frame: Week 12
BPAR was defined as the presence of clinical signs and kidney biopsy that confirmed the rejection before Week 12. Subclinical acute rejection was defined as an increase of serum creatinine at Week 12 strictly less than 10 percent (%) compared to baseline (BL) values and BPAR of Grade greater than or equal to (≥) 1 according to Banff 1997 classification at Week 12.
11 secondary outcomes
Serum Creatinine Values [Micromoles Per Liter (µmol/L)]
Time frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Creatinine Clearance Values Estimated With the Cockcroft-Gault Equation (Milliliters Per Minute [mL/Min])
Time frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Creatinine Clearance Values Estimated With the Modification of Diet in Renal Disease (MDRD) Simplified Equation
Time frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Time to Occurrence of First BPAR Between Day 0 and Week 52 - Percentage of Participants With an Event
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Time to Occurrence of First BPAR Between Day 0 and Week 52
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Percentage of Participants With at Least One BPAR at Week 12 and Week 52
Time frame: Weeks 12 and 52
Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52
Time frame: Weeks 12 and 52
Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52
Time frame: Weeks 12 and 52
Graft Loss - Percentage of Participants With an Event
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Time to Graft Loss
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Participant Survival
Time frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2015.
- 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
24 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 mycophenolate mofetil, anti-IL-2R and methylprednisolone in people with Kidney Transplantation, run by Hoffmann-La Roche at 24 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 4 inclusion and 3 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 11 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 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?
Yes. Results are posted in the registry (first posted 11 Nov 2015). 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?
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Before Week 12 or Acute Subclinical Rejection on Protocol Biopsy at Week 12 (time frame: Week 12). 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 11 Nov 2015.