Clinical trial NCT03448692: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Focal Segmental Glomerulosclerosis (FSGS)
Keywords: Proteinuria
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-02-28
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13
timeFrame: Baseline, Week 13
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From Day 1 of treatment up to 9 weeks after last dose of study treatment (up to Week 33)
measure: Number of Participants With Abnormalities in Laboratory Test Parameters
timeFrame: From Day 1 of treatment up to Week 33
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33
measure: Change From Baseline in Body Temperature
timeFrame: Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33
measure: Number of Participants With Abnormalities in Electrocardiogram (ECG)
timeFrame: Weeks 3, 7, 11, 13, 17, 21, 25, 33
measure: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 2, 5, 9 and 13
timeFrame: Baseline, Weeks 2, 5, 9 and 13
measure: Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13
timeFrame: Baseline, Weeks 3, 5, 9 and 13
measure: Serum PF-06730512 Concentration Versus Time Summary
timeFrame: 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)
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody(NAb)
timeFrame: From Day 1 of treatment up to Week 33
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic of University Alabama Birmingham Hospital
state: Alabama
city: Birmingham
country: United States
facility: Investigational Drug Service Pharmacy UAB Hosptial
state: Alabama
city: Birmingham
country: United States
facility: Clinical Research Unit at UAB Hospital
state: Alabama
city: Birmingham
country: United States
facility: UAB Nephrology Research Clinic at Paula Building
state: Alabama
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Ambulatory Infusion Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Transplant Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical and Translational Research Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine
state: California
city: Palo Alto
country: United States
facility: Clinical and Translation Research Unit
state: California
city: Palo Alto
country: United States
facility: Stanford University-Nephrology Division
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford Health Care Investigational Pharmacy
state: California
city: Stanford
country: United States
facility: Stanford University-Nephrology Division
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale Center for Clinical Investigation Hospital Research Unit
state: Connecticut
city: New Haven
country: United States
facility: Yale Nephrology Clinical Research Clinic
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale Center for Clinical Investigation - Church Street Research Unit
state: Connecticut
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Miami
country: United States
facility: University of Miami Katz Family Division of Nephrology
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Lawrenceville
country: United States
facility: Georgia Nephrology Research Institute
state: Georgia
city: Lawrenceville
country: United States
facility: Georgia Nephrology
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lenexa
country: United States
facility: Johnson County Clin Trials
state: Kansas
city: Boston
country: United States
facility: Boston Medical Center - Interventional Radiology
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center - Nephrology
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University - GCRU
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: New York
country: United States
facility: New York University Grossman School of Medicine - CTSI
state: New York
city: Chapel Hill
country: United States
facility: UNC Eastowne
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Clinical and Translational Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati at DCI McMillan Research Unit
state: Ohio
city: Cincinnati
country: United States
facility: Hoxworth Center Subspecialties Clinic
state: Ohio
city: Cincinnati
country: United States
facility: UC Health Barrett Center
state: Ohio
city: Cincinnati
country: United States
facility: UC Health Medical Arts Building
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Gardner Neuroscience Institute
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic - Investigational Drug Pharmacy
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: CarePoint East at The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Clinical Research Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Investigational Drug Services
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center- Nephrology Clinical Trials Unit
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Houston
country: United States
facility: Kidney and Hypertension Care Center, PA
state: Texas
city: Houston
country: United States
facility: Southside Pharmacy
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center (PCRC)
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Clinic - Temple South Loop
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta - Pharmacy Research Office
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta - Clinical Investigation Unit
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Pacific Nephrology Group
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital/Vancouver Coastal Health
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital/Providence Health Care
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital/Providence Health Care
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre - Kidney Care Centre at the CNIB
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-l'Ile-de-Montreal - installation Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Centre for Innovative Medicine, Research Institute of the McGill University Health Centre
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Nice Cedex 1
country: France
facility: CHU de Nice - Hopital Pasteur
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden, Medizinische Klinik III, Nephrologie
state: Saxony
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Koeln
country: Germany
facility: Uniklinik Koeln
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim
city: Villingen-Schwenningen
country: Germany
facility: Nephrologisches Zentrum Villingen-Schwenningen
city: Villingen-Schwenningen
country: Germany
facility: Sidonia Apotheke
city: Pavia PV
country: Italy
facility: Ics Maugeri Spa-Sb Irccs
state: Pavia
city: Bergamo
country: Italy
facility: Asst Papa Giovanni Xxiii
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Chiba
country: Japan
facility: National Hospital Organization Chiba-East Hospital
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr Jose Eleuterio Gonzalez"
state: Nuevo LEON
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Queretaro
country: Mexico
facility: SMIQ S de RL de CV
city: Lodz
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej
city: Lodz
country: Poland
facility: Apteka Szpitalna SPZOZ
city: Warszawa
country: Poland
facility: Centrum Zdrowia MDM
city: Warszawa
country: Poland
facility: Miedzyleski Szpital Specjalistyczny w Warszawie
city: Banska Bystrica
country: Slovakia
facility: Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
city: Banska Bystrica
country: Slovakia
facility: Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
city: Burela
country: Spain
facility: Hospital Público Da Mariña
state: Lugo
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Headington
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: Oxford
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire NHS Trust
city: London
country: United Kingdom
facility: St. George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.