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

Phase 2

Terminated

• Conditions: Focal Segmental Glomerulosclerosis (FSGS)
• Interventions: Drug: PF-06730512

• Registration Number: NCT03448692
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-22
• Study First Submitted QC: 2018-02-22
• Study First Posted: 2018-02-28
• Study Start: 2018-10-15
• Primary Completion: 2023-02-14
• Study Completion: 2023-02-14
• Results First Submitted: 2024-02-01
• Status Verified: 2024-04
• Results First Submitted QC: 2024-04-16
• Last Update Submitted: 2024-04-16
• Results First Posted: 2024-04-18
• Last Update Posted: 2024-04-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

1. Adults age 18 years and older who have a confirmed biopsy diagnosis of FSGS.
2. 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.
3. Urine protein:creatinine ratio (UPCR) greater than 1.5 g/g at screening.
4. 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

1. Diagnosis of collapsing FSGS.
2. Advanced chronic changes on renal biopsy as evidenced by greater than 50% tubulointerstitial fibrosis.
3. Organ transplant.
4. 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.
5. Body mass index (BMI) greater than 45 kg/m2.
6. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PF-06730512 Cohort 2	PF-06730512	Subjects in cohort 2 will receive dose 2 IV infusion.
PF-06730512 Cohort 1	PF-06730512	Subjects in cohort 1 will receive dose 1 Intravenous (IV) infusion.
PF-06730512 Cohort 3 (optional)	PF-06730512	Subjects in cohort 3 will receive dose 3 IV infusion.

Primary Outcome Measures

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

Name	Time	Method
Number of Participants With Abnormalities in Electrocardiogram (ECG)	Weeks 3, 7, 11, 13, 17, 21, 25, 33	ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): greater than (\>) 450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; 3) Heart rate (bpm): RR decrease \>25% and to a VR (interval between QRS wave and T wave on ECG) \>100; RR (interval between 2 successive R waves on ECG) increase \>25% and to a VR \<50; 4) Pulse rate (msec): increase \>25% and to a value \>200; 5) QT (msec): \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; 6) QRS (msec): increase \>25% and to a value \>110. Categories (timepoints) with at least 1 participant having ECG abnormality in any of the reporting arms, were reported for this outcome measure.
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)	An adverse event was considered treatment emergent relative to a given treatment if the event occurred for the first time during the investigational treatment period and was not seen prior to the start of treatment (during the lead-in period), or the event was seen prior to the start of treatment but increased in severity during treatment. Adverse events occurring during the lead-in period were considered non-treatment emergent. Events that occurred during the follow-Up period were counted as treatment emergent and attributed to the previous treatment taken.
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	UPCR is a ratio between two measured substances in urine: mmol of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function.
Number of Participants With Abnormalities in Laboratory Test Parameters	From Day 1 of treatment up to Week 33	Hemoglobin (Hg), hematocrit, erythrocytes: \<0.8\*lower limits of normal (LLN); platelets: \<0.5\*LLN\>1.75\*upper limits of normal(ULN); leukocytes (leu), glucose-fasting:\<0.6\*LLN\>1.5\*ULN; lymphocytes (lym), lym/leu, neutrophils(neu),neu/leu, protein, albumin, phosphate, free thyroxine, thyroid stimulating hormone: \<0.8\*LLN\>1.2\*ULN; basophils (bas), bas/leu, eosinophils (eos), eos/leu, monocytes(mon), mon/leu: \>1.2\*ULN; bilirubin (total, direct, indirect):\>1.5\*ULN; aspartate aminotransferase(AT), alanine AT, lactate dehydrogenase, alkaline phosphatase:\>3.0\*ULN; blood urea nitrogen, creatinine, cholesterol (total,LDL,HDL),triglycerides, Hg A1C: \>1.3\*ULN; sodium: \<0.95\*LLN\>1.05\*ULN; potassium, chloride, calcium, magnesium, bicarbonate: \<0.9\*LLLN\>1.1\*ULN; prolactin: \>1.1\*ULN; creatine kinase: \>2.0\*ULN; urobilinogen: \>=1; Urine-specific gravity: \<1.003\>1.030, pH: \<4.5 \>8, glucose,protein,bilirubin,nitrite,leukocyte esterase, ketones: \>=1.Categories with at-least 1 non-zero values are reported.
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 body weight and at baseline values were reported for this outcome measure.
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 blood pressure and at baseline values were reported for this outcome measure.
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 pulse rate and at baseline values were reported for this outcome measure.
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	Change from baseline in body temperature and at baseline values were reported for this outcome measure.
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13	Baseline, Weeks 3, 5, 9 and 13	The eGFR was calculated using 4 variable formula developed by the modification of diet in renal disease (MDRD) study group. The 4 variables needed to estimate glomerular filtration rate (GFR) using this formula were serum creatinine concentration, age, sex (for females, eGFR was multiplied by 0.742) and ethnic origin (for African-Caribbean people only, eGFR was multiplied by 1.212). Thus eGFR in milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) = 175\*(sCr/88.4)\^-1.154\*(Age)\^-0.203\*(0.742 if female)\*(1.212 if African-Caribbean). Baseline eGFR was determined predose at Week 0 (Day 1). For Baseline eGFR, the "Low eGFR" group was defined as baseline eGFR \< 45 mL/min/1.73m2, and the "High eGFR" group was defined as baseline eGFR \> 45 mL/min/1.73 m2.
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	Number of participants with positive ADA and/or NAb were reported for this outcome measure.

Trial Locations

Locations (107)

The Kirklin Clinic of University Alabama Birmingham Hospital; 🇺🇸 Birmingham, Alabama, United States

Investigational Drug Service Pharmacy UAB Hosptial; 🇺🇸 Birmingham, Alabama, United States

Clinical Research Unit at UAB Hospital; 🇺🇸 Birmingham, Alabama, United States

UAB Nephrology Research Clinic at Paula Building; 🇺🇸 Birmingham, Alabama, United States

Academic Medical Research Institute; 🇺🇸 Los Angeles, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Ambulatory Infusion Center; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Comprehensive Transplant Center; 🇺🇸 Los Angeles, California, United States

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

UCLA Clinical and Translational Research Center; 🇺🇸 Los Angeles, California, United States

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