A Study to Evaluate the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Participants Receiving Chemotherapy Treatment for Non-Myeloid Malignancies

Study Overview
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Brief Summary
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The main goal of this study is to evaluate the efficacy of roxadustat for treatment of anemia in participants with non-myeloid malignancies receiving multi-cycle treatments of myelosuppressive chemotherapy.

Detailed Description
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Participants who are eligible for participation will be randomized to roxadustat and SEPO® (recombinant human erythropoietin-α [rHuEPO-α]), and undergo a 12-week treatment period followed by a 4-week follow-up period.

Official Title
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A Randomized, Open-label, Active-controlled, Multicenter Phase 3 Study to Investigate the Efficacy and Safety of Roxadustat for Treatment of Anemia in Subjects Receiving Chemotherapy Treatment for Non-Myeloid Malignancies

Conditions
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Chemotherapy Induced Anemia

Intervention / Treatment
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* Drug: SEPO®
* Drug: Roxadustat


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of non-myeloid malignancy, by histological or cytological confirmation. Anemia related to myelosuppressive chemotherapy, defined as Hb ≤100 g/L at screening with documented participant's Hb level decrease ≥10 g/L after the initiation of chemotherapy as judged by the investigator. Planned concurrent treatment of cancer (myelosuppressive chemotherapy) for at least 8 additional weeks. Body weight ≥40 kg. Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 2. Ferritin ≥50 nanograms (ng)/milliliter (mL) and transferrin saturation (TSAT) ≥10%. Key Exclusion Criteria: Participants with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure. Participants who are only receiving hormonal products, biological products, novel immunosuppressive products (such as programmed cell death protein-1 [PD-1] and programmed death-ligand 1 [PD-L1] checkpoint inhibitors) or targeted biological or radiation therapy to treat/manage their cancer, however if chemotherapy is co-administered with these products, then it is acceptable to enroll the participant. Participants with hematocrit (HCT) ≥36%. Participants who have received an RBC transfusion or ESA within 4 weeks of randomization. Thromboembolic event (including but not limited to deep vein thrombosis [DVT], pulmonary embolism, myocardial infarction, stroke, transient ischemic attack [TIA] within previous 6 months of screening. Clinically significant anemia due to other etiologies such as iron deficiency, vitamin B12 or folate deficiency, autoimmune anemia, hemolysis, hemorrhage, or hereditary anemia such as sickle cell anemia or thalassemia. The Investigator judges that the participant will be unable to fully participate in the study and complete it for any reason, including inability to comply with study procedures and treatment, addiction, or any other relevant medical conditions. Note: Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roxadustat<br>Participants will receive roxadustat, administered orally 3 times per week (TIW) for 12 weeks to achieve Hb levels of 100-120 g/L. The starting dose will be based on the participant's weight group. The maximum dose for individual participants may not exceed 3.5 milligrams (mg)/kilogram (kg) or 400 mg TIW whichever is lower. | Drug: Roxadustat<br>* Roxadustat will be administered per dose and schedule specified in the arm description.<br>* Other names: FG-4592;|
| Active Comparator: SEPO®<br>Participants will receive SEPO®, injected subcutaneously TIW for 12 weeks to achieve Hb levels of 100-120 g/L. The starting dose will be 150 international units (IU)/kg subcutaneously TIW. | Drug: SEPO®<br>* SEPO® will be administered per dose and schedule specified in the arm description.<br>* Other names: Recombinant human erythropoietin-α [rHuEPO-α];|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin (Hb) Level From Baseline to the Level Averaged Over Weeks 9-13 | Hb levels measured from Weeks 9 through 13 will be averaged in order to provide a single measure for comparison to the baseline Hb levels. | Baseline, Weeks 9 through 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve a ≥10 Grams (g)/Liter (L) Increase in Hb From Baseline Through Week 13 |  | Baseline through Week 13 | 
| Percentage of Participants who Require Red Blood Cell (RBC) Transfusion or Hb <60 g/L or with any Hb< 60 g/L From Week 5 Through Week 13 |  | Week 5 through Week 13 | 
| Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale Score Averaged Over Weeks 9-13 | FACT-An subscale scores will be averaged over Weeks 9 through 13 in order to provide a single measure for comparison to the baseline score. | Baseline, Weeks 9 through 13 | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Subscale Score Averaged Over Weeks 9-13 | FACIT-F subscale scores will be averaged over Weeks 9 through 13 in order to provide a single measure for comparison to the baseline score. | Baseline, Weeks 9 through 13 | 
| Percentage of Participants who Require Dose Reduction or a Dose-Hold of Chemotherapy Due to Anemia |  | Baseline through Week 13 | 
| Change in Hb From Baseline up to 4 Weeks After the Last Dose of Chemotherapy During the Treatment Period |  | Baseline up to 4 weeks after the last dose of chemotherapy (up to Week 16) | 
| Change in Hb From Baseline Through Week 9 |  | Baseline through Week 9 | 
| Change in Hb From Baseline Through Week 13 |  | Baseline through Week 13 | 
| Percentage of Participants who Achieve a ≥ 15 g/L Increase in Hb From Baseline Through Week 13 |  | Baseline through Week 13 | 
| Percentage of Participants who Achieve Hb Levels ≥ 110 g/L From Baseline Through Week 13 |  | Baseline through Week 13 | 
| Percentage of Participants who Achieve an Increase in Hb of 15 g/L or Attaining a Hb of 110 g/L From Baseline Through Week 13 |  | Baseline through Week 13 | 
| Time to First RBC Transfusion |  | Baseline up to Week 13 | 
| Percentage of Participants Requiring 1 or More RBC Transfusion |  | Baseline up to Week 13 | 
| Number of RBC Transfusions Adjusted for Exposure From Baseline Through Week 13 |  | Baseline through Week 13 | 
| Percentage of Participants who Require RBC Transfusion as Medical Intervention and/or Erythropoiesis-Stimulating Agent (ESA) as a Rescue Agent |  | Baseline through Week 13 |