Clinical trial NCT03263091: Efficacy and Safety of Roxadustat for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome With Low Red Blood Cell Transfusion Burden
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Primary MDS (Very Low, Low or Intermediate IPSS-R With <5% Blasts)
Anemia
Keywords: Myelodysplastic Syndromes
Anemia
Hemoglobin (Hb)
Low Risk Myelodysplastic Syndrome
Low Risk MDS
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
name: Astellas Pharma Inc
First posted: 2017-08-28
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: OL and OL High-EPO Components: Number of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 Weeks (≥56 Consecutive Days) Since First Dose in the First 28 Weeks of Treatment
timeFrame: 28 weeks
measure: DB Component: Number of Participants Who Achieved RBC TI ≥56 Consecutive Days Since First Dose in the First 28 Weeks of Treatment
timeFrame: 28 weeks
Secondary outcomes:
measure: OL and OL High-EPO Components: Number of Participants Who Achieved TI ≥50% Reduction From Baseline in Number of Packs of Red Blood Cells (pRBC) Transfusions Over 8 Weeks
timeFrame: Baseline up to Week 8
measure: DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Since First Dose in 52 Weeks of Treatment
timeFrame: 52 weeks
measure: DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Anytime During the Study
timeFrame: Baseline up to Week 56
measure: DB Component: Number of Participants Who Achieved ≥50% Reduction From Baseline in Number of pRBC Transfusions Over 8 Weeks
timeFrame: Baseline up to Week 8
measure: DB Component: Cumulative Number of Participant Exposure Weeks (PEW) of TI Over the First 28 Weeks of Treatment
timeFrame: 28 weeks
measure: DB Component: Change From Baseline in Number of pRBC Packs Transfused Over the First 28 Weeks of Treatment
timeFrame: Baseline, Week 28
measure: DB Component: Number of Participants Who Achieved TI ≥20 Consecutive Weeks During the Study
timeFrame: Baseline up to Week 56
measure: DB Component: Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System-Short Form (PROMIS-SF) v2.0 Physical Function (PF) 10b Score at Week 9
timeFrame: Baseline, Week 9
measure: DB Component: Mean Change From Baseline in the PROMIS-SF v1.0 Fatigue 13a Score at Week 9
timeFrame: Baseline, Week 9
measure: DB Component: Mean Change From Baseline in the European Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) Visual Analogue Scale Score at Week 9
timeFrame: Baseline, Week 9
Other outcomes:
Locations:
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country: United States
facility: Investigational Site
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state: California
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state: Antwerpen
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city: Kfar Saba
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city: Monza
country: Italy
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state: Lombardia
city: Meldola
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state: Ravenna
city: Alessandria
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city: Genova
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city: Lecce
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city: Rimini
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city: Roma
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city: Torino
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city: Varese
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city: Incheon
country: Korea, Republic of
facility: Investigational Site
state: Incheon Gwang'yeogsi
city: Incheon
country: Korea, Republic of
facility: Investigational Site
state: Incheon Gwangyeogsi
city: Hwasun
country: Korea, Republic of
facility: Investigational Site
state: Jeonranamdo
city: Seoul
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state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site
city: Bialystok
country: Poland
facility: Investigational Site
city: Bydgoszcz
country: Poland
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city: Krakow
country: Poland
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city: Pila
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city: Slupsk
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city: Warszawa
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country: Russian Federation
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city: Moscow
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city: Moscow
country: Russian Federation
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city: Moscow
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country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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country: Russian Federation
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city: Sabadell
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state: Barcelona
city: Barcelona
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state: Catalunya
city: Pamplona
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state: Navarra
city: Barcelona
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
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city: Salamanca
country: Spain
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city: Sevilla
country: Spain
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city: Sevilla
country: Spain
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city: Valencia
country: Spain
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city: Ankara
country: Turkey
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city: Dikimevi
country: Turkey
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city: Izmir
country: Turkey
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city: Izmir
country: Turkey
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city: Kayseri
country: Turkey
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city: Tekirdag
country: Turkey
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city: Yenisehir
country: Turkey
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city: Boston
country: United Kingdom
facility: Investigational Site
state: Lincolnshire
city: Headington
country: United Kingdom
facility: Investigational Site
state: Oxford
city: Harrow
country: United Kingdom
facility: Investigational Site
city: London
country: United Kingdom
facility: Investigational Site
city: Manchester
country: United Kingdom
facility: Investigational Site
Study officials:
References:
citation: Henry DH, Glaspy J, Harrup R, Mittelman M, Zhou A, Carraway HE, Bradley C, Saha G, Modelska K, Bartels P, Leong R, Yu KP. Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study. Am J Hematol. 2022 Feb 1;97(2):174-184. doi: 10.1002/ajh.26397. Epub 2021 Nov 9.