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

Kidney Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02005562
• Other study ID #: ML19912
• Status: Completed
• Phase: Phase 3
• First received: December 4, 2013
• Last updated: October 12, 2015
• Start date: May 2006
• Est. completion date: March 2009

Study information

• Verified date: October 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Securite du Medicament
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 12	No
Secondary	Serum Creatinine Values [Micromoles Per Liter (µmol/L)]	The mean serum creatinine values at Weeks 2, 4, 6, 12, 16, 26, 39, and 52.	Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Weeks 12 and 52	No
Secondary	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.	Weeks 12 and 52	No
Secondary	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.	Weeks 12 and 52	No
Secondary	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.	Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No
Secondary	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.	Day 0, Weeks 2, 4, 6, 12, 16, 26, 39, and 52	No