Clinical trial NCT05210790: A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera
Official title: A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients With Polycythemia Vera
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Polycythemia Vera
Keywords: Polycythemia Vera
PV
Lead sponsor: Protagonist Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-27
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blind (Part 1a):

Subjects will be randomized in a blinded fashion to 32 weeks of rusfertide or placebo added-on to each subject's ongoing treatment for polycythemia vera.

Open-label (Part 1b + Part 2):

Open-label treatment phase during which all subjects who complete Part 1a successfully will receive rusfertide for 124 weeks.
Primary purpose: TREATMENT

Brief summary: The study is designed to evaluate the safety and efficacy of rusfertide in subjects with polycythemia vera (PV) in maintaining hematocrit control and in improving symptoms of PV.

Detailed description: Phase 3 study in approximately 250 subjects previously diagnosed with polycythemia vera (PV) who require phlebotomy on a routine basis. There is a 32-week period during which rusfertide or placebo will be added-on to each subject's ongoing therapy for polycythemia vera which may include phlebotomy only or phlebotomy plus stable doses of either of hydroxyurea, interferon and/or ruxolitinib. All subjects who successfully complete the double blind 32-week portion of the study will receive rusfertide for 124 weeks. Approximately 6 and 12 months after their last dose of rusfertide, subjects will have a post-study contact (e.g. by phone) for safety.

Eligibility criteria: Main Inclusion Criteria: All subjects must meet ALL of the following inclusion criteria to be enrolled. There are additional inclusion criteria.

* Male and female subjects aged 18 (or the country specific minimum age of consent \>18) years or older.
* Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera.
* At least 3 phlebotomies due to inadequate hematocrit control in 6 months before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization.
* CBC values immediately prior to randomization:

  1. Hematocrit \<45%,
  2. WBC 4000/μL to 20,000/μL (inclusive), and
  3. Platelets 100,000/μL to 1,000,000/μL (inclusive)
* Subjects receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen.
* Subjects treated with phlebotomy alone at randomization must have stopped cytoreductive therapy 2 to 6 months before screening.

Main Exclusion Criteria: Subjects must meet NONE of the following exclusion criteria to be enrolled. There are additional exclusion criteria.

* Clinically meaningful laboratory abnormalities at Screening.
* Subjects who require phlebotomy at hematocrit levels lower than 45%.
* Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization.
* Active or chronic bleeding within 2 months prior to randomization.
* History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer.
* Subjects with in situ or stage 1 squamous cell carcinoma of the skin, in situ or stage 1 basal cell carcinoma of the skin, or in situ melanoma of the skin identified during screen unless the cancer is adequately treated before randomization.
* Received Busulfan, Pipobroman or 32Phosphorus within 7 months prior to screening.

Primary outcomes:
measure: Proportion of subjects achieving a response who receive rusfertide compared to placebo.
timeFrame: Week 20 through Week 32
Secondary outcomes:
measure: Comparison of mean number of phlebotomies between rusfertide and placebo.
timeFrame: Week 0 to Week 32
measure: Proportion of subjects with HCT values <45% for rusfertide and placebo.
timeFrame: Week 0 to Week 32
measure: Comparison mean change from baseline in total fatigue score based on PROMIS Short Form between rusfertide and placebo.
timeFrame: Week 32
measure: Comparison of mean change from baseline in total MFSAF total score.
timeFrame: Week 32
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Infirmary Cancer Care
state: Alabama
city: Glendale
country: United States
facility: Palo Verde Hematology-Oncology
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center, Duarte
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence - Fresno
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Care
state: California
city: Irvine
country: United States
facility: City of Hope Medical Center, Lenner
state: California
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD) - Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA) - Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Pomona
country: United States
facility: Pomona Valley Hospital Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Upland
country: United States
facility: City of Hope Medical Center, Upland
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Aurora
country: United States
facility: University of Colorado - Aurora Cancer Center
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers - Boulder
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Saint Petersburg
country: United States
facility: BayCare Suncoast Medical Clinic - Hematology/Oncology
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Lake Forest
country: United States
facility: Northwestern Medicine Lake Forest Hospital
state: Illinois
city: Rolling Meadows
country: United States
facility: Northwest Oncology and Hematology
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Des Moines
country: United States
facility: Mission Cancer & Blood
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Covington
country: United States
facility: Pontchartrain Cancer Center
state: Louisiana
city: Hammond
country: United States
facility: Pontchartrain Cancer Center
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland PA (Center for Cancer & Blood Disorders)
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Reno
country: United States
facility: Cancer Care Specialists
state: Nevada
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center - BASKING RIDGE
state: New Jersey
city: Lakewood
country: United States
facility: Monmouth Medical Center Southern Campus
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center - MONMOUTH
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Cancer Center - BERGEN
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Babylon
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Bronx
country: United States
facility: Montefiore Einstein Center for Cancer Care
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center - COMMACK
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center - WESTCHESTER
state: New York
city: New Hyde Park
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - KOCH
state: New York
city: New York
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: Patchogue
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Riverhead
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Rochester
country: United States
facility: Wilmot Cancer Institute, University of Rochester
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Cancer Center - NASSAU
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute - Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Infusion Center - Kenwood
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Infusion Center - Thomas
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University (OHSU) Knight Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington - Fred Hutchinson Cancer Center
state: Washington
city: Green Bay
country: United States
facility: HSHS St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: HSHS St. Mary's Hospital
state: Wisconsin
city: Nedlands
country: Australia
facility: One Clinical Research
state: Perth
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Linz
country: Austria
facility: Kepler Universitaets Klinikum GmbH
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz
city: Vienna
country: Austria
facility: Wiener Gesundheitsverbund-Klinik Hietzing 5-Med.
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen Gmb
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Antwerp
country: Belgium
facility: ZNA Stuivenberg
city: Gent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: Campus Gasthuisberg
city: Edmonton
country: Canada
facility: The University of Alberta - Edmonton
state: Alberta
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Las Condes
country: Chile
facility: Centro Medico Inmunocel
state: Santiago
city: Providencia
country: Chile
facility: Centro de Estudios Clinicos SAGA
state: Santiago
city: Concepción
country: Chile
facility: Biocenter Centro Clinico de Investigacion
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Angers
country: France
facility: CHU Angers
state: Cedex 09
city: Paris
country: France
facility: AP-HP Hospital Necker-Enfants Malades
state: Cedex 15
city: Poitiers
country: France
facility: CHU Poitiers
state: Cedex
city: Amiens
country: France
facility: CHU Amiens Picardie - Hopital Sud
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil
city: Béziers
country: France
facility: Centre Hospitalier de Beziers
city: Paris
country: France
facility: AP-HP Hopital Saint-Louis
city: Pierre-Bénite
country: France
facility: HCL Centre Hospitalier Lyon Sud
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen - Klinik fuer Haematologie, Onkologie, Haemostaseologie und Stammzelltransplantation (Med. Klinik IV)
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
city: Greifswald
country: Germany
facility: Universitaetsmedizin Greifswald
city: Hamburg
country: Germany
facility: ONCOResearch Lerchenfeld GmbH
city: Koblenz
country: Germany
facility: InVo-Institut fuer Versorgungsforschung in der Onkologie GbR
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendelointezet
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Center Ein Karem
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center - Davidoff Hematology Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Zerifin
country: Israel
facility: Shamir Medical Center (Assaf Harofe)
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadon"
state: Forli-Cesena
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universtaria di Bologna
city: Brescia
country: Italy
facility: UOC Ematologia - ASST Spedail Civill Brescia
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, SC Ematologia (Padiglione Marcora),
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pesaro
country: Italy
facility: UOC Ematologia e Centro Trapianti AST Pesaro Urbino, Stabilimento Muraglia
city: Roma
country: Italy
facility: Fondazione Policlinico Univ. A . Gemelli IRCCS
city: Torino
country: Italy
facility: AOU San Luigi Gonzaga Orbassano
city: Torino
country: Italy
facility: AOU Citta della Salute e della Scienza di Torino
city: Varese
country: Italy
facility: Azienda ASST-SETTELAGHI, Ospedale di Circolo e Fond. Macchi di Varese Ospedael Vecchio
city: Madero
country: Mexico
facility: Centro de Estudios de Investigacion SIYODE
city: Mexico City
country: Mexico
facility: SUPERARE Centro de Infusion S.A. de C.V.
city: Mexico City
country: Mexico
facility: Boca Clinical Trials Mexico S.C. - Ciudad de Mexico
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im.ks.B.Markiewicza
city: Bydgoszcz
country: Poland
facility: MICS Centrum Medyczne Bydgoszcz
city: Gdańsk
country: Poland
facility: Klinika Hematologii I Transplantologii - Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Promed P.Lach R.Glowacki Spolka Jawna
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum, Onkologii i Traumatologii im. M Kopernika w Lodzi
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Torun
city: Warszawa
country: Poland
facility: MTZ Clinical Research Powered by Pratia
city: Wrocław
country: Poland
facility: Centrum Medyczne Melita Medical
city: Łódź
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi Oddział
city: Almada
country: Portugal
facility: Conde Hospital Garcia de Orta
city: Braga
country: Portugal
facility: Hospital de Braga
city: Lisboa
country: Portugal
facility: CHULN - Hospital de Santa Maria
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Quironsalud de Zaragoza
city: Balkiraz
country: Turkey
facility: Ankara Universitesi Tip Fakultesi Hematologi Bilim dali Ankara
state: Ankara
city: Yenimahalle
country: Turkey
facility: Gazi University Medical Faculty
state: Ankara
city: Pamukkale
country: Turkey
facility: Pamukkale University Hospitals
state: Denizli
city: Bornova
country: Turkey
facility: Ege University Hospital Department of Hematology
state: Izmir
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Medical Faculty Farabi Hospital
state: Ortahisar
city: Gaziantep
country: Turkey
facility: Sanko Universitesi tip Fakultesi Ic Hastaliklari Anabilim Dali
state: Sehitkamil
city: Gaziantep
country: Turkey
facility: Gaziantep Universitesi Sahinbey Arastirma ve Uygulama Hastanesi
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training & Research Hospital
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi Hastanesi, Dedeman Hospital
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital
state: Middlesex
city: Barnet
country: United Kingdom
facility: Barnet Hospital
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital, Royal Free London NHSFT
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
References:
citation: Pemmaraju N, Kuykendall A, Kremyanskaya M, Ginzburg Y, Ritchie E, Gotlib J, Gerds A, Palmer J, Valone F, O'Connor P, Modi N, Gupta S, Hoffman R, Verstovsek S. MPN-469 Rusfertide (PTG-300) Treatment Interruption Reverses Hematological Gains and Upon Reinitiation, Restoration of Clinical Benefit Observed in Patients With Polycythemia Vera. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S338-S339. doi: 10.1016/S2152-2650(22)01462-8.