A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)

Study Overview
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Brief Summary
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The purpose of this Phase 2 adaptive study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06730512 following multiple intravenous infusions in adult subjects with FSGS.

Official Title
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A PHASE 2, 24-WEEK, ADAPTIVE, OPEN LABEL, SEQUENTIAL COHORT TRIAL TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06730512 FOLLOWING MULTIPLE DOSES IN ADULT SUBJECTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)

Conditions
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Focal Segmental Glomerulosclerosis (FSGS)

Intervention / Treatment
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* Drug: PF-06730512


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age 18 years and older who have a confirmed biopsy diagnosis of FSGS. Estimated glomerular filtration rate (eGFR) greater than or equal to 45 ml/min/1.73 m2. If eGFR is 30 - 45 ml/min/1.73 m2, a recent biopsy (within 12 months prior to Screening) must demonstrate < 50% tubulointerstitial fibrosis. Urine protein:creatinine ratio (UPCR) greater than 1.5 g/g at screening. Treated with at least one but not more than 3 classes of immunosuppressants either alone or in combination, or has a contraindication to use of an immunosuppressant or is intolerant to an immunosuppressant per investigator judgment. Exclusion Criteria: Diagnosis of collapsing FSGS. Advanced chronic changes on renal biopsy as evidenced by greater than 50% tubulointerstitial fibrosis. Organ transplant. History of malignancy, with the exception of basal or squamous cell carcinoma that has been treated and fully resolved for a minimum of 5 years. Body mass index (BMI) greater than 45 kg/m2. Subjects with a history of prior treatment with or use of interferon, lithium, pamidronate, mTOR inhibitors (eg, sirolimus), testosterone/anabolic steroids, anthracycline (eg, doxorubicin), heroin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06730512 Cohort 1<br>Subjects in cohort 1 will receive dose 1 Intravenous (IV) infusion. | Drug: PF-06730512<br>* Subjects in cohort 1 will receive Dose 1 Intravenous infusion (IV). Subjects in cohort 2 will receive Dose 2 IV. Subjects in cohort 3 will receive Dose 3 IV infusion.<br>|
| Experimental: PF-06730512 Cohort 2<br>Subjects in cohort 2 will receive dose 2 IV infusion. | Drug: PF-06730512<br>* Subjects in cohort 1 will receive Dose 1 Intravenous infusion (IV). Subjects in cohort 2 will receive Dose 2 IV. Subjects in cohort 3 will receive Dose 3 IV infusion.<br>|
| Experimental: PF-06730512 Cohort 3 (optional)<br>Subjects in cohort 3 will receive dose 3 IV infusion. | Drug: PF-06730512<br>* Subjects in cohort 1 will receive Dose 1 Intravenous infusion (IV). Subjects in cohort 2 will receive Dose 2 IV. Subjects in cohort 3 will receive Dose 3 IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline to Week 13 in Urinary Protein to Creatinine Ratio (UPCR). |  | Baseline to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in UPCR |  | Baseline to Weeks 3, 5 and 9 and beyond Week 13, as applicable | 
| Percentage change from baseline in estimated glomerular filtration rate (eGFR) |  | Baseline to Weeks 3, 5, 9, 13 and beyond as applicable | 
| Number of Adverse Events by Severity |  | Baseline to Day 225 | 
| Number of subjects with laboratory safety tests (Hematology, Clinical Chemistry, Urinalysis) abnormality |  | Baseline to Day 225 | 
| Number of subjects with change in body weight |  | Baseline to Day 225 | 
| Number of subjects with increased blood pressure |  | Baseline to Day 225 | 
| Number of subjects with increased body temperature |  | Baseline to Day 225 | 
| Number of subjects with significant changes in pulse rate |  | Baseline to Day 225 | 
| Number of subjects with ECG abnormalities |  | Baseline to Day 225 | 
| Serum concentration of PF-06730512 |  | Day 1 to Day 225 | 
| Number of subjects with development of anti drug antibody (ADA) and neutralizing antibody (NAb) |  | Day 1 to Day 225 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proteinuria