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

Focal Segmental Glomerulosclerosis (FSGS) Clinical Trial

— PODO  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03448692
• Other study ID #: C0221002
• Secondary ID: 2019-003607-35RO
• Status: Terminated
• Phase: Phase 2
• Start date: October 15, 2018
• Est. completion date: February 14, 2023

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 47
• Est. completion date: February 14, 2023
• Est. primary completion date: February 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis (FSGS)
• Glomerulosclerosis, Focal Segmental

Intervention

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.

Locations

Country	Name	City	State
Canada	University of Alberta - Clinical Investigation Unit	Edmonton	Alberta
Canada	University of Alberta - Pharmacy Research Office	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	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	CHU de Quebec-Universite Laval	Quebec
Canada	Sunnybrook Health Sciences Centre - Kidney Care Centre at the CNIB	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	Pacific Nephrology Group	Vancouver	British Columbia
Canada	St. Paul's Hospital/Providence Health Care	Vancouver	British Columbia
Canada	St. Paul's Hospital/Providence Health Care	Vancouver	British Columbia
Canada	Vancouver General Hospital/Vancouver Coastal Health	Vancouver	British Columbia
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	Hopital Henri Mondor	Creteil
France	CHU de Nice - Hopital Pasteur	Nice Cedex 1
France	Hopital Necker - Enfants Malades	Paris
Germany	Universitaetsklinikum Aachen	Aachen
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Universitätsklinikum Dresden, Medizinische Klinik III, Nephrologie	Dresden	Saxony
Germany	Universitaetsklinikum Erlangen	Erlangen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Uniklinik Koeln	Koeln
Germany	Universitaetsklinikum Mannheim	Mannheim
Germany	Nephrologisches Zentrum Villingen-Schwenningen	Villingen-Schwenningen
Germany	Sidonia Apotheke	Villingen-Schwenningen
Italy	Asst Papa Giovanni Xxiii	Bergamo
Italy	Ics Maugeri Spa-Sb Irccs	Pavia PV	Pavia
Japan	National Hospital Organization Chiba-East Hospital	Chiba
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Osaka University Hospital	Suita	Osaka
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City
Mexico	Hospital Universitario "Dr Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON
Mexico	SMIQ S de RL de CV	Queretaro
Poland	Apteka Szpitalna SPZOZ	Lodz
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Lodz
Poland	Centrum Zdrowia MDM	Warszawa
Poland	Miedzyleski Szpital Specjalistyczny w Warszawie	Warszawa
Slovakia	Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica	Banska Bystrica
Slovakia	Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica	Banska Bystrica
Slovakia	Narodny ustav detskych chorob	Bratislava
Slovakia	Univerzitna nemocnica Bratislava	Bratislava
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Público Da Mariña	Burela	Lugo
Spain	Hospital Universitario 12 de Octubre	Madrid
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	University Hospitals Coventry & Warwickshire NHS Trust	Coventry
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Headington	Oxford
United Kingdom	Hammersmith Hospital	London
United Kingdom	St. George's University Hospitals NHS Foundation Trust	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United States	Clinical Research Unit at UAB Hospital	Birmingham	Alabama
United States	Investigational Drug Service Pharmacy UAB Hosptial	Birmingham	Alabama
United States	The Kirklin Clinic of University Alabama Birmingham Hospital	Birmingham	Alabama
United States	UAB Nephrology Research Clinic at Paula Building	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Boston Medical Center - Interventional Radiology	Boston	Massachusetts
United States	Boston Medical Center - Nephrology	Boston	Massachusetts
United States	Boston University - GCRU	Boston	Massachusetts
United States	UNC Clinical and Translational Research Center	Chapel Hill	North Carolina
United States	UNC Eastowne	Chapel Hill	North Carolina
United States	Hoxworth Center Subspecialties Clinic	Cincinnati	Ohio
United States	UC Health Barrett Center	Cincinnati	Ohio
United States	UC Health Medical Arts Building	Cincinnati	Ohio
United States	University of Cincinnati at DCI McMillan Research Unit	Cincinnati	Ohio
United States	University of Cincinnati Gardner Neuroscience Institute	Cincinnati	Ohio
United States	The Cleveland Clinic	Cleveland	Ohio
United States	The Cleveland Clinic - Investigational Drug Pharmacy	Cleveland	Ohio
United States	CarePoint East at The Ohio State University	Columbus	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	The Ohio State University Clinical Research Center	Columbus	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	Henry Ford Hospital	Detroit	Michigan
United States	Kidney and Hypertension Care Center, PA	Houston	Texas
United States	Prolato Clinical Research Center (PCRC)	Houston	Texas
United States	Southside Pharmacy	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	St. Luke's Hospital	Kansas City	Missouri
United States	Georgia Nephrology	Lawrenceville	Georgia
United States	Georgia Nephrology Research Institute	Lawrenceville	Georgia
United States	Johnson County Clin Trials	Lenexa	Kansas
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	UCLA Department of Medicine	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	University of Miami Hospital and Clinics	Miami	Florida
United States	University of Miami Katz Family Division of Nephrology	Miami	Florida
United States	Yale Center for Clinical Investigation - Church Street Research Unit	New Haven	Connecticut
United States	Yale Center for Clinical Investigation Hospital Research Unit	New Haven	Connecticut
United States	Yale Nephrology Clinical Research Clinic	New Haven	Connecticut
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Yale University School of Medicine - Yale-New Haven Hospital	New Haven	Connecticut
United States	New York University Grossman School of Medicine - CTSI	New York	New York
United States	Clinical and Translation Research Unit	Palo Alto	California
United States	Stanford University-Nephrology Division	Palo Alto	California
United States	University of California, San Francisco	San Francisco	California
United States	Stanford Health Care Investigational Pharmacy	Stanford	California
United States	Stanford University	Stanford	California
United States	Stanford University-Nephrology Division	Stanford	California
United States	Baylor Scott & White Clinic - Temple South Loop	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  France,  Germany,  Italy,  Japan,  Mexico,  Poland,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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

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