Kidney Transplantation, Cytomegalovirus Infections
Conditions
Brief summary
This open-label, single arm study will evaluate the tolerability and efficacy of Valcyte (valganciclovir) in the prevention of cytomegalovirus disease in pediatric renal transplant recipients. After transplantation, patients (aged 4 months to 16 years) will receive Valcyte orally daily for up to 200 days post-transplant and will be followed for 52 weeks post-transplantation.
Interventions
Oral, daily for up to 200 days.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Months to 16 Years
Healthy volunteers
No
Inclusion criteria
* Children, 4 months to 16 years of age * Patient has received a kidney transplant * At risk of developing cytomegalovirus disease * Adequate hematological and renal function * Able to tolerate oral medication * Negative pregnancy test for females of childbearing potential
Exclusion criteria
* Allergic or significant adverse reaction to acyclovir, valacyclovir or ganciclovir in the past * Severe uncontrolled diarrhea (more than 5 watery stools per day) * Liver enzyme elevation of more than five times the upper limit of normal for aspartate aminotransferase \[AST (SGOT)\] or alanine aminotransferase \[ALT (SGPT)\] * Patient requires use of any protocol prohibited concomitant medication * Previous participation in this clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs | 52 weeks | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Pre-existing conditions which worsen during a study were reported as AEs. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator | 52 weeks | A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia by each study center as part of the clinical assessment required for diagnosis of CMV infection. CMV disease included CMV syndrome or tissue invasive CMV. CMV syndrome required fever ≥ 38 degrees Celsius, severe malaise, leukopenia on 2 separate measurements, atypical lymphocytosis ≥ 5%, thrombocytopenia, elevation of hepatic transaminases and presence of CMV in blood. Tissue Invasive CMV required evidence of localized CMV infection in a biopsy or other appropriate symptom and relevant symptoms or signs of organ dysfunction. |
| Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | 52 weeks | Blood samples were sent to a central lab for the quantitative assessment of CMV viral load (amount of CMV in the blood) by an FDA-approved molecular-based assay. The number of participants in each category is reported in copies/milliliter (CP/mL). CMV DNA is detected in all categories \< 150 CP/mL and above. |
| Number of Participants With Biopsy Proven Rejection | 52 Weeks | Renal biopsies were performed as medically indicated. Biopsies were assessed histologically using the updated Banff criteria 1997. |
| Number of Participants With Cytomegalovirus (CMV) Infection in the First 52 Weeks Post-Transplant as Assessed by the Investigator | 52 weeks | A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia (presence of CMV in the blood) by each study center as part of the clinical assessment required for diagnosis of CMV infection. |
| Number of Participants With Death | 52 Weeks | — |
| Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes) | 52 Weeks | All patients with measurable CMV had both UL54 and UL97 genes sequenced to assess for known CMV resistance to ganciclovir. |
| Number of Participants With Graft Loss | 52 Weeks | Graft loss was defined as the institution of chronic dialysis (at least 6 consecutive weeks), transplant nephrectomy, or retransplantation. |
Countries
Australia, Brazil, France, Germany, Mexico, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valganciclovir Participants received a once daily oral dose (solution or tablets) of valganciclovir starting within 10 days of kidney transplant for up to 200 days post-transplant. Dose (in mg) was calculated using the algorithm \[7 \* Body Surface Area \* Creatinine Clearance\]. | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period | Adverse Event | 6 |
| Treatment Period | Patient did not receive study drug | 1 |
| Treatment Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Valganciclovir |
|---|---|
| Age, Customized ≥ 12 Years | 32 Participants 1.3 |
| Age, Customized > 2 to < 12 Years | 18 Participants 2.5 |
| Age, Customized ≤ 2 Years | 6 Participants 0.5 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 56 |
| serious Total, serious adverse events | 41 / 56 |
Outcome results
Primary
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Pre-existing conditions which worsen during a study were reported as AEs. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Time frame: 52 weeks
Population: Safety Population included all enrolled patients who received at least one dose of study medication and had at least one post-baseline assessment of safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir | Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs | Adverse Events | 56 Participants |
| Valganciclovir | Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs | Serious Adverse Events | 41 Participants |
| Valganciclovir | Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) or Withdrawal Due to AEs | Withdrawals due to AE | 6 Participants |
Secondary
Number of Participants With Biopsy Proven Rejection
Renal biopsies were performed as medically indicated. Biopsies were assessed histologically using the updated Banff criteria 1997.
Time frame: 52 Weeks
Population: ITT population included all enrolled patients who had taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir | Number of Participants With Biopsy Proven Rejection | ≤ 2 Years | 1 Participants |
| Valganciclovir | Number of Participants With Biopsy Proven Rejection | >2 to <12 Years | 1 Participants |
| Valganciclovir | Number of Participants With Biopsy Proven Rejection | ≥ 12 Years | 3 Participants |
Secondary
Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator
A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia by each study center as part of the clinical assessment required for diagnosis of CMV infection. CMV disease included CMV syndrome or tissue invasive CMV. CMV syndrome required fever ≥ 38 degrees Celsius, severe malaise, leukopenia on 2 separate measurements, atypical lymphocytosis ≥ 5%, thrombocytopenia, elevation of hepatic transaminases and presence of CMV in blood. Tissue Invasive CMV required evidence of localized CMV infection in a biopsy or other appropriate symptom and relevant symptoms or signs of organ dysfunction.
Time frame: 52 weeks
Population: Intent-to-treat (ITT) population included all enrolled patients who had taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir | Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator | CMV Syndrome | 1 Participants |
| Valganciclovir | Number of Participants With Cytomegalovirus (CMV) Disease in the First 52 Weeks Post-Transplant as Assessed by the Investigator | Tissue Invasive CMV | 0 Participants |
Secondary
Number of Participants With Cytomegalovirus (CMV) Infection in the First 52 Weeks Post-Transplant as Assessed by the Investigator
A polymerase chain reaction (PCR) based assay or antigenaemia assay was used for the qualitative assessment of CMV viremia (presence of CMV in the blood) by each study center as part of the clinical assessment required for diagnosis of CMV infection.
Time frame: 52 weeks
Population: Intent-to-treat (ITT) population included all enrolled patients who had taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir | Number of Participants With Cytomegalovirus (CMV) Infection in the First 52 Weeks Post-Transplant as Assessed by the Investigator | 3 Participants |
Secondary
Number of Participants With Death
Time frame: 52 Weeks
Population: ITT population included all enrolled patients who had taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir | Number of Participants With Death | 0 Participants |
Secondary
Number of Participants With Graft Loss
Graft loss was defined as the institution of chronic dialysis (at least 6 consecutive weeks), transplant nephrectomy, or retransplantation.
Time frame: 52 Weeks
Population: ITT population included all enrolled patients who had taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valganciclovir | Number of Participants With Graft Loss | 0 Participants |
Secondary
Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes)
All patients with measurable CMV had both UL54 and UL97 genes sequenced to assess for known CMV resistance to ganciclovir.
Time frame: 52 Weeks
Population: All patients meeting the resistance analysis criteria are included into the resistance analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir | Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes) | UL54 | 0 Participants |
| Valganciclovir | Number of Participants With Known Ganciclovir Resistance (Mutations in Either UL54 or UL97 Genes) | UL97 | 1 Participants |
Secondary
Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant
Blood samples were sent to a central lab for the quantitative assessment of CMV viral load (amount of CMV in the blood) by an FDA-approved molecular-based assay. The number of participants in each category is reported in copies/milliliter (CP/mL). CMV DNA is detected in all categories \< 150 CP/mL and above.
Time frame: 52 weeks
Population: ITT population included all enrolled patients who had taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Valganciclovir | Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | No CMV DNA Detected | 30 Participants |
| Valganciclovir | Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | < 150 CP/mL | 16 Participants |
| Valganciclovir | Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | 150 to 1,000 CP/mL | 6 Participants |
| Valganciclovir | Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | 1,001 to 5,000 CP/mL | 3 Participants |
| Valganciclovir | Number of Participants With Peak Cytomegalovirus (CMV) Viral Load up to Week 52 Post-Transplant | > 5,000 CP/mL | 1 Participants |