Sirolimus for Focal Segmental Glomerulosclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00040508
• Date of registration: 26/06/2002
• Prospective Registration: No
• Primary sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Public title: Sirolimus for Focal Segmental Glomerulosclerosis
• Scientific title: Sirolimus for Focal Segmental Glomerulosclerosis
• Date of first enrolment: June 2002
• Target sample size: 30
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00040508
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

INCLUSION CRITERIA

Renal biopsy showing FSGS, including all variants with the exception of HIV-associated
FSGS.

Nephrotic range proteinuria, defined as 24 hour urine protein excretion greater than or
equal to 3.5 g/d in adults and children weighing greater than or equal to 70 kg and
greater than or equal to 50 mg/kg in adults or children weighing less than 70 kg.
Proteinuria will be assessed with at least three 24 hour urine collections obtained during
the baseline period (for these collections, there is no minimum period, the maximum period
is 3 months prior to study entry, and the most recent must be within 1 month of entry).
These measurements will be obtained while on angiotensin antagonist therapy (if tolerant
of this medication) and will exclude urine collections judged inadequate based on
creatinine appearance. For patients in the drug overlap group, baseline proteinuria will
be determined from patient's records demonstrating on at least one urine collection,
proteinuria greater than 3.5 g/d while off immunosuppressive therapy.

Ability and willingness to provide informed consent (adults greater than or equal to 18.0
years) or assent (children greater than or equal to 13.0 years).

Completion of a therapeutic trial of at least one of the following, without sustained CR:

Steroid therapy for greater than or equal to 8 weeks, either daily or alternate day or
intermittent (oral or parenteral)

Cyclosporine or tacrolimus or mycophenolate mofetil for greater than or equal to 3 months

Cyclophosphamide (either oral or intravenous) or chlorambucil for greater than or equal to
three months

EXCLUSION CRITERIA

Intolerance to sirolimus or prior use of sirolimus for FSGS.

Estimated GFR less than 30 mL/min/1.73m(2). The rational is that 1) sirolimus therapy is
most likely to be beneficial during the early phase of FSGS, before progressive fibrosis
in the glomeruli and interstitium has become the dominant abnormality and may be
irreversible, and 2) we wish to enroll patients who are unlikely to progress to ESRD
within the one year treatment period.

Patients following renal transplant. We wish to rest sirolimus with a minimum of other
immunosuppressive therapy.

Children less than 13.0 years.

Uncontrolled hypertension, defined as BP greater than 140/90 on greater than 25% of
measurements.

Pregnancy, lactation, or unwillingness or inability to practice effective contraception.
The rationale is that the safety of sirolimus in pregnancy has not been determined and
excretion via breast milk may alter pharmacokinetics.

Chronic active infections requiring treatment, including untreated reactive PPD, or any
infection sufficiently severe require parenteral antibiotics during the preceding 30 days.
The rationale is that immunosuppression may exacerbate infection.

HIV-1 infection or hepatitis B infection or hepatitis C infection (defined as detectable
RNA off anti-viral therapy). The rationale is that immunosuppression may exacerbate
infection.

Chronic liver disease sufficiently severe to impair sirolimus metabolism; this would
include prolonged pro-thrombin time.

Basal thrombocytopenia less than 100,000 cells/microliter or absolute neutrophil count
less than 2000 cells/microliter or hematocrit less than 30. The rationale is that
sirolimus may further lower cell counts.

Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal cell
carcinoma of the skin. The rationale is that cancer progression may be accelerated by
immunosuppression.



Age minimum: N/A
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Focal Glomerulosclerosis

Intervention(s)

Drug: Sirolimus

Secondary ID(s)

02-DK-0235

020235

Source(s) of Monetary Support

Please refer to primary and secondary sponsors