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

FibroGen

Status and phase: Terminated; Phase 3

Conditions: Anemia; Primary MDS (Very Low, Low or Intermediate IPSS-R With <5% Blasts)

Treatments: Drug: Roxadustat; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03263091

FGCL-4592-082

Details and patient eligibility

About

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.

Full 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.

Enrollment: 184 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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184 participants in 2 patient groups, including a placebo group

Roxadustat

Experimental group

Description:

Open-label, lead-in: Participants will receive sequential escalating roxadustat doses (1.5 milligrams/kilograms \[mg/kg\], 2.0 mg/kg and 2.5 mg/kg), three times a week (TIW) based upon their actual weight at the randomization visit to identify the starting dose for double-blind period. Double-blind: Participants will receive roxadustat 2.5 mg/kg TIW based upon their body weight for a duration of 52 weeks. Open-label: Participants with high serum erythropoietin levels (\>400 milli-international units \[mIU\]/milliliter \[mL\] mIU/mL) will receive roxadustat 2.5 mg/kg TIW based upon their body weight for a duration of 52 weeks.

Treatment:

Drug: Roxadustat

Placebo

Placebo Comparator group

Description:

Double-blind: Participants will receive placebo matching to roxadustat for a duration of 52 weeks.

Treatment:

Drug: Placebo