Chemotherapy Induced Anemia
Conditions
Keywords
Anemia, Chemotherapy induced anemia, Myelosuppressive chemotherapy, Non-Myeloid malignances
Brief summary
The purpose of this study is to find out if roxadustat (also known as FG-4592) is safe and effective for the treatment of anemia in participants receiving chemotherapy treatment for cancer.
Detailed description
This study consists of three periods: 1. Screening Period up to 28 days 2. Treatment Period of up to16 weeks 3. A Follow-up period of 4 weeks.
Interventions
DRUGRoxadustat
Roxadustat will be administered per schedule specified in the arm description.
Sponsors
AstraZeneca
Astellas Pharma Inc
Kyntra Bio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of non-myeloid malignancy 2. Anemia caused by cancer treatment (myelosuppressive chemotherapy) defined as Hb ≤10.0 grams (g)/deciliter (dL) at screening 3. Planned concurrent treatment of cancer with chemotherapy for at least 8 additional weeks 4. Estimated life expectancy ≥ 6 months at enrollment (Day 1)
Exclusion criteria
1. Participants with cancer receiving chemotherapy when the anticipated outcome is cure 2. Participants who are only receiving hormonal products, biological products, cancer immunotherapy or radiation therapy to treat/manage their cancer 3. History of leukemia 4. Participants who have received an RBC transfusion or erythropoietic therapy within 4 weeks of enrollment 5. Use of any investigational drug within 8-weeks prior to treatment with roxadustat 6. Clinically significant anemia due to other etiologies 7. Cardiovascular risks, such as myocardial infarction, stroke, heart failure or thromboembolic event (for example, deep vein thrombosis \[DVT\] or pulmonary embolism) within previous 6 months of screening 8. Clinically significant or uncontrolled ongoing autoimmune disease (for example, rheumatoid arthritis, Crohn's disease, celiac disease, etc.) 9. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Change in Hb Within 16 Weeks From Baseline Without Red Blood Cell (RBC) Transfusion | Baseline, up to Week 16 | Baseline Hb was defined as the mean of the assessments from central lab prior to first dose of the study treatment, which included up to 2 latest screening values prior to Day 1 and a value on Day 1. All central lab assessments from Day 1 to end of treatment (EOT) or early termination (ET) were included in the evaluation of this endpoint. Hb values within 4 weeks after an RBC transfusion were excluded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hb From Baseline at Weeks 9, 13, and 16 (Without RBC Transfusion) | Baseline, Weeks 9, 13, and 16 | Baseline Hb was defined as the mean of the assessments from central lab prior to first dose of the study treatment, which included up to 2 latest screening values prior to Day 1 and a value on Day 1. |
| Percentage of Participants Who Achieved a ≥1 g/dL Increase in Hb From Baseline Through Week 16 | Baseline through Week 16 | The 95% confidence interval (CI) was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded. |
| Time to Achieve a ≥1 g/dL Increase in Hb From Baseline Through Week 16 | Baseline through Week 16 | Median was calculated using Kaplan-Meier product limit method. 95% CI was calculated using the method of Brookmeyer and Crowley. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion were excluded. |
| Mean Change in Hb Level From Baseline to Week 16 (Without RBC Transfusion) | Baseline, Week 16 | Baseline Hb was defined as the mean of the assessments from central lab prior to first dose of the study treatment, which included up to 2 latest screening values prior to Day 1 and a value on Day 1. Mean Hb during treatment was computed using the mean area-under-the-curve trapezoid method, from Day 1 to EOT or ET Hb assessment. |
| Percentage of Participants Who Achieved a Hematopoietic Response | Baseline through Week 16 | Hematopoietic response was defined as an increase in Hb of 1.5 g/dL from baseline or attaining a Hb of 11 g/dL. The 95% CI was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded. |
| Percentage of Participants Who Achieved a ≥2 g/dL Increase in Hb From Baseline Through Week 16 | Baseline through Week 16 | The 95% CI was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded. |
| Percentage of Participants Who Had an RBC Transfusion From Beginning of Week 5 (Day 29) to Week 16 | Week 5 to Week 16 | — |
| Percentage of Participants Who Achieved a ≥1.5 g/dL Increase in Hb From Baseline Through Week 16 | Baseline through Week 16 | The 95% CI was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat Participants received roxadustat as an oral tablet, TIW for up to a maximum of 16 weeks. The starting dose of roxadustat was 2.0 mg/kg. The dose was updated with Amendment 3 (dated 22 May 2020) for newly enrolled participants by 1 level that is, from 2.0 mg/kg to 2.5 mg/kg level to achieve an improved Hb response. | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 13 |
| Overall Study | Other than specified | 6 |
| Overall Study | Progressive Disease | 2 |
| Overall Study | Withdrawal by Subject | 12 |
Baseline characteristics
| Characteristic | Roxadustat |
|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 10.44 |
| Baseline Hemoglobin (Hb) | 8.59 grams (g)/deciliter (dL) STANDARD_DEVIATION 0.956 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 76 Participants |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 92 |
| other Total, other adverse events | 71 / 92 |
| serious Total, serious adverse events | 40 / 92 |
Outcome results
Primary
Maximum Change in Hb Within 16 Weeks From Baseline Without Red Blood Cell (RBC) Transfusion
Baseline Hb was defined as the mean of the assessments from central lab prior to first dose of the study treatment, which included up to 2 latest screening values prior to Day 1 and a value on Day 1. All central lab assessments from Day 1 to end of treatment (EOT) or early termination (ET) were included in the evaluation of this endpoint. Hb values within 4 weeks after an RBC transfusion were excluded.
Time frame: Baseline, up to Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Maximum Change in Hb Within 16 Weeks From Baseline Without Red Blood Cell (RBC) Transfusion | 2.47 g/dL | Standard Deviation 1.51 |
Secondary
Change in Hb From Baseline at Weeks 9, 13, and 16 (Without RBC Transfusion)
Baseline Hb was defined as the mean of the assessments from central lab prior to first dose of the study treatment, which included up to 2 latest screening values prior to Day 1 and a value on Day 1.
Time frame: Baseline, Weeks 9, 13, and 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change in Hb From Baseline at Weeks 9, 13, and 16 (Without RBC Transfusion) | Change at Week 9 | 1.43 g/dL | Standard Deviation 1.421 |
| Roxadustat | Change in Hb From Baseline at Weeks 9, 13, and 16 (Without RBC Transfusion) | Change at Week 13 | 2.15 g/dL | Standard Deviation 1.921 |
| Roxadustat | Change in Hb From Baseline at Weeks 9, 13, and 16 (Without RBC Transfusion) | Change at Week 16 | 2.52 g/dL | Standard Deviation 1.7 |
Secondary
Mean Change in Hb Level From Baseline to Week 16 (Without RBC Transfusion)
Baseline Hb was defined as the mean of the assessments from central lab prior to first dose of the study treatment, which included up to 2 latest screening values prior to Day 1 and a value on Day 1. Mean Hb during treatment was computed using the mean area-under-the-curve trapezoid method, from Day 1 to EOT or ET Hb assessment.
Time frame: Baseline, Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Change in Hb Level From Baseline to Week 16 (Without RBC Transfusion) | 1.20 g/dL | Standard Deviation 1.012 |
Secondary
Percentage of Participants Who Achieved a ≥1.5 g/dL Increase in Hb From Baseline Through Week 16
The 95% CI was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded.
Time frame: Baseline through Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants Who Achieved a ≥1.5 g/dL Increase in Hb From Baseline Through Week 16 | 73.0 percentage of participants |
Secondary
Percentage of Participants Who Achieved a ≥1 g/dL Increase in Hb From Baseline Through Week 16
The 95% confidence interval (CI) was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded.
Time frame: Baseline through Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants Who Achieved a ≥1 g/dL Increase in Hb From Baseline Through Week 16 | 82.0 percentage of participants |
Secondary
Percentage of Participants Who Achieved a ≥2 g/dL Increase in Hb From Baseline Through Week 16
The 95% CI was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded.
Time frame: Baseline through Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants Who Achieved a ≥2 g/dL Increase in Hb From Baseline Through Week 16 | 60.7 percentage of participants |
Secondary
Percentage of Participants Who Achieved a Hematopoietic Response
Hematopoietic response was defined as an increase in Hb of 1.5 g/dL from baseline or attaining a Hb of 11 g/dL. The 95% CI was based on the exact method of Clopper-Pearson method. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion was excluded.
Time frame: Baseline through Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants Who Achieved a Hematopoietic Response | 75.3 percentage of participants |
Secondary
Percentage of Participants Who Had an RBC Transfusion From Beginning of Week 5 (Day 29) to Week 16
Time frame: Week 5 to Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants Who Had an RBC Transfusion From Beginning of Week 5 (Day 29) to Week 16 | 14.5 percentage of participants |
Secondary
Time to Achieve a ≥1 g/dL Increase in Hb From Baseline Through Week 16
Median was calculated using Kaplan-Meier product limit method. 95% CI was calculated using the method of Brookmeyer and Crowley. All central lab assessments from Day 1 to EOT or ET were included in the analysis. Hb values within 4 weeks after an RBC transfusion were excluded.
Time frame: Baseline through Week 16
Population: Full analysis set included all enrolled participants who received at least 1 dose of roxadustat, had a baseline Hb and at least 1 central lab Hb assessment during the treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Roxadustat | Time to Achieve a ≥1 g/dL Increase in Hb From Baseline Through Week 16 | 41.0 days |