Efficacy and Safety of Roxadustat for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome With Low Red Blood Cell Transfusion Burden

Primary MDS (Very Low, Low or Intermediate IPSS-R With <5% Blasts) Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients With Lower Risk Myelodysplastic Syndrome (MDS) With Low Red Blood Cell (RBC) Transfusion Burden (LTB)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03263091
• Other study ID #: FGCL-4592-082
• Status: Terminated
• Phase: Phase 3
• Start date: September 7, 2017
• Est. completion date: June 22, 2023

Study information

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

Clinical Trial Summary

The purpose of this study is to determine whether FG-4592 is safe and effective in the treatment of anemia in participants with lower risk MDS and low red blood cell transfusion burden.

Description:

This study includes an Open-Label Lead in, a Double-Blind component, and an Open-Label High Erythropoietin component. There is a screening period of up to 42 days followed by a treatment period of 52 weeks and a 4-week end of treatment assessment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 184
• Est. completion date: June 22, 2023
• Est. primary completion date: March 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Diagnosis of primary MDS classified by the International Prognostic Scoring System - Revised (IPSS-R) as very low, low or intermediate risk with <5% bone marrow blasts. There is no minimum time from diagnosis to registration/randomization except to allow for proper IPSS-R classification to be made (within 16 weeks prior to randomization), and to show transfusion dependence for participants in both portions of the study.

• RBC transfusion of either 2-4 pRBC units during the 8 weeks prior to registration/randomization or 1 pRBC in two consecutive periods of 8 weeks within the 16 weeks prior to registration/randomization. Open-Label Lead-in participants only, the requirement to demonstrate transfusion dependence can also be met by a Principal Investigator starting this particular participant on pRBC transfusion during the screening period.

• No restriction on prior use of recombinant erythropoietins or analogues (erythropoiesis-stimulating agents [ESAs]), except no ESA use within 8 weeks prior to Day 1 registration/randomization.

• Hemoglobin (Hb) =10.0 grams/deciliter (g/dL) during screening

• Eastern Cooperative Oncology Group (ECOG) of 0-2 at screening

Key Exclusion Criteria:

• Diagnosis of secondary MDS associated with prior chemotherapy, extensive radiation therapy (>25% of bone marrow reserve), and or/other significant chemical or radiation exposure

• Significant myelofibrosis (>2+ fibrosis)

• MDS associated with 5q(del) cytogenetic abnormality

• Screen serum erythropoietin level > 400 milli-international units (mIU)/milliliter (mL) • Clinically significant anemia, as determined by the investigator, due to non-MDS etiologies such as iron deficiency, vitamin B12 or folate deficiency, autoimmune or hereditary hemolysis or anemia or hemorrhage or hereditary anemia such as sickle cell anemia or thalassemia.

Related Conditions & MeSH terms

• Anemia
• Myelodysplastic Syndromes
• Preleukemia
• Primary MDS (Very Low, Low or Intermediate IPSS-R With <5% Blasts)
• Syndrome

Intervention

Drug:
• Roxadustat
Oral tablets
• Placebo
Oral tablets

Locations

Country	Name	City	State
Australia	Investigational Site	Darlinghurst	New South Wales
Australia	Investigational Site	Hobart	Tasmania
Australia	Investigational Site	Liverpool	New South Wales
Australia	Investigational Site	South Brisbane	Queensland
Australia	Investigational Site	Victoria Park	Saint Albans
Belgium	Investigational Site	Brugge	West-Vlaanderen
Belgium	Investigational Site	Brussels
Belgium	Investigational Site	Bruxelles	Brussels Capital Region
Belgium	Investigational Site	Hasselt	Limburg
Belgium	Investigational Site	Wilrijk	Antwerpen
Belgium	Investigational Site	Yvoir
Canada	Investigational Site	London	Ontario
Canada	Investigational Site	Vancouver	British Columbia
Denmark	Investigational Site	Odense
France	Investigational Site	Grenoble	Isère
France	Investigational Site	Nice	Alpes-Maritimes
France	Investigational Site	Paris
France	Investigational Site	Tours
Germany	Investigational Site	Dresden	Sachsen
Germany	Investigational Site	Düsseldorf
Germany	Investigational Site	Düsseldorf
Germany	Investigational Site	Freiburg	Baden-Wurttemberg
Germany	Investigational Site	Leipzig	Sachsen
Germany	Investigational Site	Munchen	Bayern
Germany	Investigational Site	Münster	Nordrhein-Westfalen
India	Investigational Site	Kolkata	West Bengal
India	Investigational Site	Vellore	Tamil Nadu
Israel	Investigational Site	Haifa
Israel	Investigational Site	Kfar Saba	HaMerkaz
Israel	Investigational Site	Nahariya	HaZafon
Israel	Investigational Site	Ramat Gan
Israel	Investigational Site	Tel Aviv
Israel	Investigational site	Tel HaShomer
Israel	Investigational Site	Zerifin	HaMerkaz
Italy	Investigational Site	Alessandria
Italy	Investigational Site	Bologna
Italy	Investigational Site	Firenze
Italy	Investigational Site	Genova
Italy	Investigational Site	Lecce
Italy	Investigational Site	Meldola	Ravenna
Italy	Investigational Site	Milano
Italy	Investigational Site	Monza	Lombardia
Italy	Investigational Site	Reggio Calabria
Italy	Investigational Site	Rimini
Italy	Investigational Site	Roma
Italy	Investigational Site	Terni
Italy	Investigational Site	Torino
Italy	Investigational Site	Varese
Korea, Republic of	Investigational Site	Hwasun	Jeonranamdo
Korea, Republic of	Investigational Site	Incheon	Incheon Gwang'yeogsi
Korea, Republic of	Investigational Site	Incheon	Incheon Gwangyeogsi
Korea, Republic of	Investigational Site	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Investigational Site	Seoul
Poland	Investigational Site	Bialystok
Poland	Investigational Site	Bydgoszcz
Poland	Investigational Site	Krakow
Poland	Investigational Site	Pila
Poland	Investigational Site	Skorzewo
Poland	Investigational Site	Slupsk
Poland	Investigational Site	Warszawa
Russian Federation	Investigational Site	Kaluga
Russian Federation	Investigational Site	Moscow
Russian Federation	Investigational Site	Moscow
Russian Federation	Investigational Site	Moscow
Russian Federation	Investigational Site	Omsk
Russian Federation	Investigational Site	Saint Petersburg
Russian Federation	Investigational Site	Saint Petersburg
Russian Federation	Investigational Site	Saint Petersburg
Russian Federation	Investigational Site	St. Petersburg
Spain	Investigational Site	Barcelona	Catalunya
Spain	Investigational Site	Barcelona
Spain	Investigational Site	Barcelona
Spain	Investigational Site	Barcelona
Spain	Investigational Site	Madrid
Spain	Investigational Site	Madrid
Spain	Investigational Site	Madrid
Spain	Investigational Site	Pamplona	Navarra
Spain	Investigational Site	Sabadell	Barcelona
Spain	Investigational Site	Salamanca
Spain	Investigational Site	Sevilla
Spain	Investigational Site	Sevilla
Spain	Investigational Site	Valencia
Turkey	Investigational Site	Ankara
Turkey	Investigational Site	Dikimevi
Turkey	Investigational Site	Izmir
Turkey	Investigational Site	Izmir
Turkey	Investigational Site	Kayseri
Turkey	Investigational Site	Tekirdag
Turkey	Investigational Site	Yenisehir
United Kingdom	Investigational Site	Boston	Lincolnshire
United Kingdom	Investigational Site	Harrow
United Kingdom	Investigational Site	Headington	Oxford
United Kingdom	Investigational Site	London
United Kingdom	Investigational Site	Manchester
United States	Investgational site	Atlanta	Georgia
United States	Investigational Site	Augusta	Georgia
United States	Investigational Site	Bakersfield	California
United States	Investigational Site	Beverly Hills	California
United States	Investigational Site	Burbank	California
United States	Investigational Site	Canton	Ohio
United States	Investigational Site	Charleston	South Carolina
United States	Investigational Site	Charlotte	North Carolina
United States	Investigational Site	Charlottesville	Virginia
United States	Investigational Site	Cleveland	Ohio
United States	Investigational Site	Cleveland	Ohio
United States	Investigational Site	Encino	California
United States	Investigational Site	Grand Junction	Colorado
United States	Investigational Site	Houston	Texas
United States	Investigational Site	Laguna Hills	California
United States	Investigational Site	Los Angeles	California
United States	Investigational Site	Los Angeles	California
United States	Investigational Site	Mayfield Heights	Ohio
United States	Investigational Site	Oceanside	California
United States	Investigational Site	Pasadena	California
United States	Investigational Site	Pembroke Pines	Florida
United States	Investigational Site	Philadelphia	Pennsylvania
United States	Investigational Site	Saint Louis	Missouri
United States	Investigational Site	Santa Maria	California
United States	Investigational Site	Torrance	California
United States	Investigational Site	Valencia	California
United States	Investigational Site	Ventura	California
United States	Investigational Site	Westlake Village	California
United States	Investiational Site	Weston	Florida
United States	Investigational Site	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
FibroGen	Astellas Pharma Inc, AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  India,  Israel,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Achieve Transfusion Independence (TI) =56 Consecutive Days in the First 28 Weeks of Treatment		28 weeks
Secondary	Percentage of Participants who Achieve TI =56 Consecutive Days Anytime During the Study		Weeks 28 and 52
Secondary	Percentage of Participants who Achieve =50% Reduction From Baseline in Number of RBC Transfusion Over Any 8 Weeks		Weeks 28 and 52
Secondary	Cumulative Number of Participant-Exposure-Week of TI		Weeks 28 and 52
Secondary	Number of Packs of Red Blood Cells (pRBC) Packs Transfused Compared to Baseline		Weeks 28 and 52
Secondary	Percentage of Participants who Achieved TI for > 20 Weeks (140 Days)		Weeks 28 and 52
Secondary	Mean Change From Baseline in Physical Function as Measured by Patient Reported Outcomes Measurement Information System (PROMIS)		Baseline, Weeks 9, 17, 28, 52 and 56
Secondary	Mean Change From Baseline in PROMIS Fatigue Score		Baseline, Weeks 9, 17, 28, 52 and 56
Secondary	Mean Change From Baseline in EuroQol Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) Assessment Score		Baseline, Weeks 9, 17, 28, 52 and 56