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)

Pfizer107 sites in 1 country47 target enrollmentOctober 15, 2018

ConditionsFocal Segmental Glomerulosclerosis (FSGS)

InterventionsPF-06730512

DrugsPF-06730512

Overview

Phase: Phase 2
Intervention: PF-06730512
Conditions: Focal Segmental Glomerulosclerosis (FSGS)
Sponsor: Pfizer
Enrollment: 47
Locations: 107
Primary Endpoint: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

October 15, 2018

End Date

February 14, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

Eligibility Criteria

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 m
•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/m
•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.

Arms & Interventions

PF-06730512 Cohort 1

Subjects in cohort 1 will receive dose 1 Intravenous (IV) infusion.

Intervention: PF-06730512

PF-06730512 Cohort 2

Subjects in cohort 2 will receive dose 2 IV infusion.

Intervention: PF-06730512

PF-06730512 Cohort 3 (optional)

Subjects in cohort 3 will receive dose 3 IV infusion.

Intervention: PF-06730512

Outcomes

Primary Outcomes

Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13

Time Frame: Baseline, Week 13

UPCR is a ratio between two measured substances in urine: milligram of protein per millimole (mmol) of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function.

Secondary Outcomes

Number of Participants With Abnormalities in Electrocardiogram (ECG)(Weeks 3, 7, 11, 13, 17, 21, 25, 33)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From Day 1 of treatment up to 9 weeks after last dose of study treatment (up to Week 33))
Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 2, 5, 9 and 13(Baseline, Weeks 2, 5, 9 and 13)
Number of Participants With Abnormalities in Laboratory Test Parameters(From Day 1 of treatment up to Week 33)
Change From Baseline in Body Weight(Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33)
Change From Baseline in Blood Pressure(Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33)
Change From Baseline in Pulse Rate(Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33)
Change From Baseline in Body Temperature(Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33)
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13(Baseline, Weeks 3, 5, 9 and 13)
Serum PF-06730512 Concentration Versus Time Summary(For 12-Week treatment(WT):pre-dose on Day1,8,15,29,43,57,71,follow-up(Fup)visit on Day85,99,113,141,For 24-WT:pre-dose on Day1,8,15,29,43,57,71,85,99,113,127,141,155,Fup visit on Day169,183,197,225;1hour post-dose on Day1,71,155(only applicable for 24-WT))
Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody(NAb)(From Day 1 of treatment up to Week 33)