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

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)

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 Overview

• Status: Terminated
• Conditions: Focal Segmental Glomerulosclerosis (FSGS)
• Intervention / Treatment: Drug: PF-06730512

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • CHU de Quebec-Universite Laval
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
    • Edmonton, Alberta, Canada, T6G 1Z1
      • University of Alberta - Pharmacy Research Office
    • Edmonton, Alberta, Canada, T6G 287
      • University of Alberta - Clinical Investigation Unit
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Pacific Nephrology Group
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital/Vancouver Coastal Health
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital/Providence Health Care
    • Vancouver, British Columbia, Canada, V6Z 2K8
      • St. Paul's Hospital/Providence Health Care
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
    • Toronto, Ontario, Canada, M4G 3E8
      • Sunnybrook Health Sciences Centre - Kidney Care Centre at the CNIB
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSS de l'Est-de-l'Ile-de-Montreal - installation Hopital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H4A 3J1
      • Centre for Innovative Medicine, Research Institute of the McGill University Health Centre
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Praha 2, Czechia, 128 08
    • Vseobecna Fakultni Nemocnice V Praze
• France
  • Creteil, France, 94010
    • Hopital Henri MONDOR
  • Nice Cedex 1, France, 06001
    • CHU de Nice - Hopital Pasteur
  • Paris, France, 75015
    • Hôpital Necker - Enfants Malades
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum Aachen
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Koeln, Germany, 50937
    • Uniklinik Koeln
  • Mannheim, Germany, 68167
    • Universitaetsklinikum Mannheim
  • Villingen-Schwenningen, Germany, 78052
    • Nephrologisches Zentrum Villingen-Schwenningen
  • Villingen-Schwenningen, Germany, 78052
    • Sidonia Apotheke
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitätsklinikum Dresden, Medizinische Klinik III, Nephrologie
• Italy
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII
  • Pavia
    • Pavia PV, Pavia, Italy, 27100
      • Ics Maugeri Spa-Sb Irccs
• Japan
  • Chiba, Japan, 260-8712
    • National Hospital Organization Chiba-East Hospital
  • Niigata, Japan, 951-8510
    • Niigata University Medical & Dental Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
  • Queretaro, Mexico, 76070
    • SMIQ S de RL de CV
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Hospital Universitario "Dr Jose Eleuterio Gonzalez"
• Poland
  • Lodz, Poland, 92-213
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej
  • Lodz, Poland, 92-216
    • Apteka Szpitalna SPZOZ
  • Warszawa, Poland, 04-749
    • Miedzyleski Szpital Specjalistyczny w Warszawie
  • Warszawa, Poland, 00-631
    • Centrum Zdrowia MDM
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
  • Banska Bystrica, Slovakia, 975 01
    • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
  • Bratislava, Slovakia, 831 01
    • Univerzitna nemocnica Bratislava
  • Bratislava, Slovakia, 833 40
    • Narodny ustav detskych chorob
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Lugo
    • Burela, Lugo, Spain, 27880
      • Hospital Público da Mariña
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Coventry, United Kingdom, CV2 2DX
    • University Hospitals Coventry & Warwickshire NHS Trust
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, SW17 0QT
    • St. George's University Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 7LE
      • Oxford University Hospitals NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The Kirklin Clinic of University Alabama Birmingham Hospital
    • Birmingham, Alabama, United States, 35249
      • Investigational Drug Service Pharmacy UAB Hosptial
    • Birmingham, Alabama, United States, 35294
      • Clinical Research Unit at UAB Hospital
    • Birmingham, Alabama, United States, 35294
      • UAB Nephrology Research Clinic at Paula Building
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Department of Medicine
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Comprehensive Transplant Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Ambulatory Infusion Center
    • Los Angeles, California, United States, 90095
      • UCLA Clinical and Translational Research Center
    • Palo Alto, California, United States, 94304
      • Clinical and Translation Research Unit
    • Palo Alto, California, United States, 94304
      • Stanford University-Nephrology Division
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
    • Stanford, California, United States, 94305
      • Stanford Health Care Investigational Pharmacy
    • Stanford, California, United States, 94305
      • Stanford University-Nephrology Division
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
    • New Haven, Connecticut, United States, 06510
      • Yale Nephrology Clinical Research Clinic
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine - Yale-New Haven Hospital
    • New Haven, Connecticut, United States, 06519
      • Yale Center for Clinical Investigation - Church Street Research Unit
    • New Haven, Connecticut, United States, 06511
      • Yale New Haven Hospital
    • New Haven, Connecticut, United States, 06510
      • Yale Center for Clinical Investigation Hospital Research Unit
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
    • Miami, Florida, United States, 33136
      • University of Miami Katz Family Division of Nephrology
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Georgia Nephrology Research Institute
    • Lawrenceville, Georgia, United States, 30046
      • Georgia Nephrology
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin Trials
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center - Interventional Radiology
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center - Nephrology
    • Boston, Massachusetts, United States, 02118
      • Boston University - GCRU
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
  • New York
    • New York, New York, United States, 10016
      • New York University Grossman School of Medicine - CTSI
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Eastowne
    • Chapel Hill, North Carolina, United States, 27599-7064
      • UNC Clinical and Translational Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45206
      • University of Cincinnati at DCI McMillan Research Unit
    • Cincinnati, Ohio, United States, 45219
      • Hoxworth Center Subspecialties Clinic
    • Cincinnati, Ohio, United States, 45219
      • UC Health Barrett Center
    • Cincinnati, Ohio, United States, 45219
      • UC Health Medical Arts Building
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati Gardner Neuroscience Institute
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic - Investigational Drug Pharmacy
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Investigational Drug Services
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Columbus, Ohio, United States, 43203
      • CarePoint East at The Ohio State University
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Clinical Research Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center- Nephrology Clinical Trials Unit
  • Texas
    • Houston, Texas, United States, 77004
      • Kidney and Hypertension Care Center, PA
    • Houston, Texas, United States, 77030
      • Southside Pharmacy
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center (PCRC)
    • Temple, Texas, United States, 76502
      • Baylor Scott & White Clinic - Temple South Loop

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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)	Number of participants with positive ADA and/or NAb were reported for this outcome measure.	From Day 1 of treatment up to Week 33

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Beck LH Jr, Berasi SP, Copley JB, Gorman D, Levy DI, Lim CN, Henderson JM, Salant DJ, Lu W. PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis. Kidney Int Rep. 2021 Apr 3;6(6):1629-1633. doi: 10.1016/j.ekir.2021.03.892. eCollection 2021 Jun.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): February 14, 2023
• Study Completion (Actual): February 14, 2023

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 28, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Proteinuria
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulosclerosis, Focal Segmental
• Other Study ID Numbers: C0221002; 2019-003607-35 (EudraCT Number); ROBO2 (Other Identifier: Alias Study Number); PODO (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No