A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 47
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PF-06730512 Cohort 3 (optional) PF-06730512 Subjects in cohort 3 will receive dose 3 IV infusion. 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.
- 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 Cleveland Clinic - Investigational Drug Pharmacy
🇺🇸Cleveland, Ohio, United States
The Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
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
Cedars-Sinai Ambulatory Infusion Center
🇺🇸Los Angeles, California, United States
Academic Medical Research Institute
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical 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 Department of Medicine
🇺🇸Los Angeles, California, United States
UCLA Clinical and Translational Research Center
🇺🇸Los Angeles, California, United States
Stanford University-Nephrology Division
🇺🇸Stanford, California, United States
Clinical and Translation Research Unit
🇺🇸Palo Alto, California, United States
Stanford Health Care Investigational Pharmacy
🇺🇸Stanford, California, United States
Stanford University
🇺🇸Stanford, California, United States
Yale Center for Clinical Investigation Hospital Research Unit
🇺🇸New Haven, Connecticut, United States
Yale University School of Medicine - Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale Nephrology Clinical Research Clinic
🇺🇸New Haven, Connecticut, United States
Yale Center for Clinical Investigation - Church Street Research Unit
🇺🇸New Haven, Connecticut, United States
University of Miami Hospital and Clinics
🇺🇸Miami, Florida, United States
University of Miami Katz Family Division of Nephrology
🇺🇸Miami, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Georgia Nephrology Research Institute
🇺🇸Lawrenceville, Georgia, United States
Georgia Nephrology
🇺🇸Lawrenceville, Georgia, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Boston Medical Center - Interventional Radiology
🇺🇸Boston, Massachusetts, United States
Boston Medical Center - Nephrology
🇺🇸Boston, Massachusetts, United States
Clinical Research Consultants, LLC
🇺🇸Kansas City, Missouri, United States
Boston University - GCRU
🇺🇸Boston, Massachusetts, United States
St. Luke's Hospital
🇺🇸Kansas City, Missouri, United States
University of Cincinnati at DCI McMillan Research Unit
🇺🇸Cincinnati, Ohio, United States
UNC Clinical and Translational Research Center
🇺🇸Chapel Hill, North Carolina, United States
UNC Eastowne
🇺🇸Chapel Hill, North Carolina, United States
New York University Grossman School of Medicine - CTSI
🇺🇸New York, New York, United States
UC Health Barrett Center
🇺🇸Cincinnati, Ohio, United States
Hoxworth Center Subspecialties Clinic
🇺🇸Cincinnati, Ohio, United States
UC Health Medical Arts Building
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Gardner Neuroscience Institute
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Investigational Drug Services
🇺🇸Columbus, Ohio, United States
The Ohio State University Wexner Medical Center- Nephrology Clinical Trials Unit
🇺🇸Columbus, Ohio, United States
The Ohio State University Clinical Research Center
🇺🇸Columbus, Ohio, United States
Kidney and Hypertension Care Center, PA
🇺🇸Houston, Texas, United States
Southside Pharmacy
🇺🇸Houston, Texas, United States
Baylor Scott & White Clinic - Temple South Loop
🇺🇸Temple, Texas, United States
Prolato Clinical Research Center (PCRC)
🇺🇸Houston, Texas, United States
University of Alberta - Pharmacy Research Office
🇨🇦Edmonton, Alberta, Canada
University of Alberta - Clinical Investigation Unit
🇨🇦Edmonton, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Vancouver General Hospital/Vancouver Coastal Health
🇨🇦Vancouver, British Columbia, Canada
Sunnybrook Health Sciences Centre - Kidney Care Centre at the CNIB
🇨🇦Toronto, Ontario, Canada
CHU de Quebec-Universite Laval
🇨🇦Quebec, Canada
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Hopital Henri Mondor
🇫🇷Creteil, France
Centre for Innovative Medicine, Research Institute of the McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
CIUSSS de l'Est-de-l'Ile-de-Montreal - installation Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
CHU de Nice - Hopital Pasteur
🇫🇷Nice Cedex 1, France
Hopital Necker - Enfants Malades
🇫🇷Paris, France
Universitätsklinikum Dresden, Medizinische Klinik III, Nephrologie
🇩🇪Dresden, Saxony, Germany
Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Charite - Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Universitaetsklinikum Erlangen
🇩🇪Erlangen, Germany
Uniklinik Koeln
🇩🇪Koeln, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
Universitaetsklinikum Mannheim
🇩🇪Mannheim, Germany
Nephrologisches Zentrum Villingen-Schwenningen
🇩🇪Villingen-Schwenningen, Germany
Sidonia Apotheke
🇩🇪Villingen-Schwenningen, Germany
Ics Maugeri Spa-Sb Irccs
🇮🇹Pavia PV, Pavia, Italy
Asst Papa Giovanni Xxiii
🇮🇹Bergamo, Italy
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
SMIQ S de RL de CV
🇲🇽Queretaro, Mexico
Apteka Szpitalna SPZOZ
🇵🇱Lodz, Poland
Miedzyleski Szpital Specjalistyczny w Warszawie
🇵🇱Warszawa, Poland
Centrum Zdrowia MDM
🇵🇱Warszawa, Poland
Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
🇸🇰Banska Bystrica, Slovakia
Univerzitna nemocnica Bratislava
🇸🇰Bratislava, Slovakia
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Headington, Oxford, United Kingdom
St. George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Johnson County Clin Trials
🇺🇸Lenexa, Kansas, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
St. Paul's Hospital/Providence Health Care
🇨🇦Vancouver, British Columbia, Canada
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
🇲🇽Mexico City, Mexico
University of California, San Francisco
🇺🇸San Francisco, California, United States
Pacific Nephrology Group
🇨🇦Vancouver, British Columbia, Canada
Hospital Público Da Mariña
🇪🇸Burela, Lugo, Spain
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
Yale University
🇺🇸New Haven, Connecticut, United States
University Health Network
🇨🇦Toronto, Ontario, Canada
National Hospital Organization Chiba-East Hospital
🇯🇵Chiba, Japan
Samodzielny Publiczny Zaklad Opieki Zdrowotnej
🇵🇱Lodz, Poland
Hospital Universitario "Dr Jose Eleuterio Gonzalez"
🇲🇽Monterrey, Nuevo LEON, Mexico
Narodny ustav detskych chorob
🇸🇰Bratislava, Slovakia
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
CarePoint East at The Ohio State University
🇺🇸Columbus, Ohio, United States
University Hospitals Coventry & Warwickshire NHS Trust
🇬🇧Coventry, United Kingdom