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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
47
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.
Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at 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.
Time frame: Baseline, Week 13
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: From Day 1 of treatment up to 9 weeks after last dose of study treatment (up to Week 33)
Number of Participants With Abnormalities in Laboratory Test Parameters
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.
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Time frame: From Day 1 of treatment up to Week 33
Change From Baseline in Body Weight
Change from baseline in body weight and at baseline values were reported for this outcome measure.
Time frame: 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
Change from baseline in blood pressure and at baseline values were reported for this outcome measure.
Time frame: 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
Change from baseline in pulse rate and at baseline values were reported for this outcome measure.
Time frame: 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
Change from baseline in body temperature and at baseline values were reported for this outcome measure.
Time frame: Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33
Number of Participants With Abnormalities in Electrocardiogram (ECG)
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.
Time frame: Weeks 3, 7, 11, 13, 17, 21, 25, 33
Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at 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.
Time frame: Baseline, Weeks 2, 5, 9 and 13
Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at 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.
Time frame: Baseline, Weeks 3, 5, 9 and 13
Serum PF-06730512 Concentration Versus Time Summary
Time frame: 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)
Number of participants with positive ADA and/or NAb were reported for this outcome measure.
Time frame: From Day 1 of treatment up to Week 33