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OPERA Study: A Study of Two Dosing Regimens of CellCept (Mycophenolate Mofetil) in Kidney Transplant Patients.

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ClinicalTrials.gov Identifier: NCT02005562
Recruitment Status : Completed
First Posted : December 9, 2013
Results First Posted : November 11, 2015
Last Update Posted : November 11, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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 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.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Drug: mycophenolate mofetil Drug: anti-IL-2R Drug: methylprednisolone Drug: cyclosporine Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : May 2006
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009


Arm Intervention/treatment
Experimental: Mycophenolate Mofetil, Adapted Dose
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.
Drug: mycophenolate mofetil
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).
Other Name: CellCept

Drug: anti-IL-2R
Induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion.

Drug: methylprednisolone
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.
Other Name: Solumedrol

Drug: cyclosporine
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

Active Comparator: Mycophenolate Mofetil, Fixed Dose
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.
Drug: mycophenolate mofetil
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.
Other Name: CellCept

Drug: anti-IL-2R
Induction by IL-2R was administered at Day 0 per standard of care at the site at the investigators discretion.

Drug: methylprednisolone
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.
Other Name: Solumedrol

Drug: cyclosporine
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Serum Creatinine Values [Micromoles Per Liter (µmol/L)] [ Time Frame: Weeks 2, 4, 6, 12, 16, 26, 39, and 52 ]
    The mean serum creatinine values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52.

  2. 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 ]
    The mean creatinine clearance values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52 estimated using the Cockcroft-Gault equation.

  3. 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 ]
    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.

  4. 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 ]
    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.

  5. 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 ]
    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.

  6. Percentage of Participants With at Least One BPAR at Week 12 and Week 52 [ Time Frame: Weeks 12 and 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.

  7. Graft Histology - Percentage of Participants With at Least One Borderline Lesion at Week 12 and Week 52 [ Time Frame: Weeks 12 and 52 ]
    Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.

  8. Graft Histology - Percentage of Participants With at Least One Chronic Graft Nephropathy at Week 12 and Week 52 [ Time Frame: Weeks 12 and 52 ]
    Participants were censored at the date of last treatment, date of last contact or withdrawal, and date of death.

  9. Graft Loss - Percentage of Participants With an Event [ Time Frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 ]
    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.

  10. Time to Graft Loss [ Time Frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 ]
    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.

  11. Participant Survival [ Time Frame: Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52 ]
    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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

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): NCT02005562


Locations
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France
Bordeaux, France, 33076
Brest, France, 29609
Clermont-ferrand, France, 63000
Creteil, France, 94010
Dijon, France, 21079
La Tronche, France, 38700
Le Kremlin-bicetre, France, 94275
Lille, France, 59037
Limoges, France, 87042
Montpellier, France, 34295
Nantes, France, 44035
Nice, France, 06002
Paris, France, 75018
Paris, France, 75475
Paris, France, 75743
Paris, France, 75970
Poitiers, France, 86021
Rennes, France, 35033
Salouel, France, 80480
Strasbourg, France, 67091
Suresnes, France, 92151
Toulouse, France, 31054
Tours, France, 37044
Vandoeuvre-les-nancy, France, 54511
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Chair: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02005562     History of Changes
Other Study ID Numbers: ML19912
First Posted: December 9, 2013    Key Record Dates
Results First Posted: November 11, 2015
Last Update Posted: November 11, 2015
Last Verified: October 2015

Additional relevant MeSH terms:
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Cyclosporins
Cyclosporine
Mycophenolic Acid
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone
Methylprednisolone Acetate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents