Iron Deficiency Anemia (IDA)
Conditions
Brief summary
The main objective of this study is to compare the safety, effect on quality of life, and resource utilization of Injectafer vs. intravenous (IV) iron standard of care (SOC) for the treatment of iron deficiency anemia (IDA) in an infusion center setting. The study will also assess the ability of baseline serum hepcidin levels to predict if subjects will have a clinically meaningful hemoglobin response to oral iron therapy or to IV iron therapy.
Detailed description
The main objective of this study is to compare the safety, effect on quality of life, and resource utilization of Injectafer vs. intravenous (IV) iron standard of care (SOC) for the treatment of iron deficiency anemia (IDA) in an infusion center setting. The study will also assess the ability of baseline serum hepcidin levels to predict if subjects will have a clinically meaningful hemoglobin response to oral iron therapy for 28 days or to IV iron therapy.
Interventions
DRUGInjectafer
2 doses at 15 mg/kg for a maximum single dose of 750 mg given 7 days apart for a total of up to 1500 mg.
DRUGSOC
Sponsors
American Regent, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects ≥ 18 years of age and able to give informed consent. * Iron deficiency is the primary etiology of anemia. * If using erythropoiesis stimulating agent (ESA), the subject must be using a dose consistent with package insert that has been stable for at least 30 days. * Doses of potential myelosuppressive medications have been stable for at least 30 days. * Females at risk of pregnancy must agree to use an acceptable form of birth control and have a negative serum or urine pregnancy test on the first day of dosing.
Exclusion criteria
* Hypersensitivity reaction to any component of Injectafer. * Requires dialysis for treatment of chronic kidney disease (CKD). * No evidence of iron deficiency. * During the 10 day period prior to screening has been treated with intravenous iron. * During the 30 day period prior to screening has been treated with a red red blood cell transfusion. * Any non-viral infection. * Known positive hepatitis with evidence of active disease. * Received an investigational drug within 30 days of screening. * Alcohol or drug abuse within the past 6 months. * Hemochromatosis or other iron storage disorders. * Estimated life expectancy of less than 6 months, or for cancer patients, an Eastern Cooperative Oncology Group (ECOG) Performance Status greater than 1. * Pregnant or actively trying to become pregnant (a definitive negative result on a serum or urine pregnancy test performed on the first day of dosing will be required for study enrollment by any women of childbearing potential). * Any other laboratory abnormality, medical condition or psychiatric disorders which in the opinion of the investigator would put the subject's disease management at risk or may result in the subject being unable to comply with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Multidimensional Assessment of Fatigue (MAF) Scores | Baseline to Day 30 | The MAF scale has 16 items that measure the Global Fatigue Index (GFI), a composite score of Items 1 through 15. Items 1 through 14 were measured on a scale of 1 to 10, with 1 = not at all and 10 = a great deal. Items 15 and 16 had categorical responses: degree of agreement from 0 to 4, with 0=no days and 4=every day. Then, a Global Fatigue Index (GFI) is calculated by summing specific items and averaging others. The final GFI score ranges from 1 (no fatigue) to 50 (severe fatigue). The resulting score is given as the mean value. |
| Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Baseline and Day 30 | The WPAI consisted of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed other reasons; 4 = hours actually worked; 5 = degree health affected productivity while working using a scale of 0 to 10, with 0 = PROBLEM had no effect on my work and 10 = PROBLEM completely prevented me from working; 6 = degree health affected productivity in regular unpaid activities using a scale of 0 to 10, with 0 = PROBLEM had no effect on my daily activities and 10 = PROBLEM completely prevented me from doing my daily activities. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. |
| Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Baseline and Day 30 | Participants rated 14 items with 4 domains. Scores for item 1 to 3, 9 to 11 and 14 ranged from 1=extremely dissatisfied to 7=extremely satisfied. Items 5 to 8, 12, 13 ranged from 1=extremely dissatisfied to 5=not at all dissatisfied. Item 4 was scored as: 0=No, 1=Yes. Effectiveness measured as (\[{sum of item 1 to 3} - 3\]/18)\*100; if 1 question (Q) was missing: (\[{sum of item 1 to 3} -2\]/12)\*100. Side-effect measured as if item 4=No, score=100; if not then (\[{sum of item 5 to 8} -4\]/16)\*100; if 1 Q was missing: (\[{sum of item 5 to 8} -3\]/12)\*100. Convenience measured as (\[{sum of item 9 to 11} -3\]/18)\*100; if 1 Q was missing: (\[{sum of item 9 to 11} - 2\]/12)\*100. Global satisfaction as (\[{sum of item 12 to 14} -3\]/14)\*100; if item 12 or 13 was missing: (\[{sum of item 12 to 14} -2\]/10)\*100; if item 14 was missing: (\[{sum of item 12 and 13} -2\]/8)\*100. All domains had scale of 0 (no satisfaction) to 100 (best level of satisfaction), higher score equals greater satisfaction |
| Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Baseline and Day 30 | The SF-12 is a multipurpose short form to measure health status. There are 10 domains: Physical Composite Index (score range from 0-100); Physical Functioning Index (score range from 0-100); Role Limitation Physical Index (score range 0-100); Pain Index Score (score range from 0-100); General Health Index (score range from 0-100); Mental Health Composite Index (score range from 1-100); Vitality Index (score range from 0-100); Social Functioning Index (score rang 0-100); Role Limitation Emotional Index (score range 0-100); and SF-12 Mental Health Index (score range from 0-100), the higher the score means a better outcome. The overall scale and sub-scales were calculated with the standard SF-12 formulas. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Injectafer 2 doses at 15 mg/kg for a maximum single dose of 750 mg given 7 days apart for a total of up to 1500 mg.
Injectafer: 2 doses at 15 mg/kg for a maximum single dose of 750 mg given 7 days apart for a total of up to 1500 mg. | 513 |
| IV Iron Standard of Care (SOC) At a dose and administration regimen as determined by the study site investigator
SOC | 512 |
| Total | 1,025 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 18 | 16 |
| Overall Study | Not Defined | 4 | 10 |
| Overall Study | Physician Decision | 3 | 4 |
| Overall Study | Withdrawal by Subject | 28 | 13 |
Baseline characteristics
| Characteristic | Injectafer | IV Iron Standard of Care (SOC) | Total |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 16.58 | 55.7 years STANDARD_DEVIATION 16.68 | 56.5 years STANDARD_DEVIATION 16.64 |
| Region of Enrollment United States | 513 Participants | 512 Participants | 1025 Participants |
| Sex: Female, Male Female | 421 Participants | 409 Participants | 830 Participants |
| Sex: Female, Male Male | 92 Participants | 103 Participants | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 513 | 1 / 512 |
| other Total, other adverse events | 28 / 513 | 21 / 512 |
| serious Total, serious adverse events | 4 / 513 | 1 / 512 |
Outcome results
Primary
Multidimensional Assessment of Fatigue (MAF) Scores
The MAF scale has 16 items that measure the Global Fatigue Index (GFI), a composite score of Items 1 through 15. Items 1 through 14 were measured on a scale of 1 to 10, with 1 = not at all and 10 = a great deal. Items 15 and 16 had categorical responses: degree of agreement from 0 to 4, with 0=no days and 4=every day. Then, a Global Fatigue Index (GFI) is calculated by summing specific items and averaging others. The final GFI score ranges from 1 (no fatigue) to 50 (severe fatigue). The resulting score is given as the mean value.
Time frame: Baseline to Day 30
Population: Change from baseline to Day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Injectafer | Multidimensional Assessment of Fatigue (MAF) Scores | -8.8 units on a scale | Standard Deviation 11.38 |
| IV Iron Standard of Care (SOC) | Multidimensional Assessment of Fatigue (MAF) Scores | -8.1 units on a scale | Standard Deviation 11.28 |
Primary
Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores.
The SF-12 is a multipurpose short form to measure health status. There are 10 domains: Physical Composite Index (score range from 0-100); Physical Functioning Index (score range from 0-100); Role Limitation Physical Index (score range 0-100); Pain Index Score (score range from 0-100); General Health Index (score range from 0-100); Mental Health Composite Index (score range from 1-100); Vitality Index (score range from 0-100); Social Functioning Index (score rang 0-100); Role Limitation Emotional Index (score range 0-100); and SF-12 Mental Health Index (score range from 0-100), the higher the score means a better outcome. The overall scale and sub-scales were calculated with the standard SF-12 formulas.
Time frame: Baseline and Day 30
Population: Change from Baseline to Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Overall Physical Health Score | 3.3 units on a scale | Standard Deviation 7.94 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Role Limitation Physical | 4.0 units on a scale | Standard Deviation 9.53 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | General Health | 3.2 units on a scale | Standard Deviation 9.86 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Vitality | 7.7 units on a scale | Standard Deviation 11.36 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Pain | 1.6 units on a scale | Standard Deviation 10.03 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Social Functioning | 3.6 units on a scale | Standard Deviation 12.19 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Overall Mental Health Score | 3.7 units on a scale | Standard Deviation 10.31 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Role Limitation Emotion | 2.7 units on a scale | Standard Deviation 12.69 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Mental Health | 2.9 units on a scale | Standard Deviation 10.1 |
| Injectafer | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Physical Functioning | 3.6 units on a scale | Standard Deviation 10.42 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Mental Health | 3.3 units on a scale | Standard Deviation 9.62 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | General Health | 2.5 units on a scale | Standard Deviation 9.84 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Pain | 2.5 units on a scale | Standard Deviation 10.52 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Overall Physical Health Score | 3.1 units on a scale | Standard Deviation 8.33 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Overall Mental Health Score | 3.7 units on a scale | Standard Deviation 10.39 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Physical Functioning | 3.4 units on a scale | Standard Deviation 10.45 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Vitality | 7.0 units on a scale | Standard Deviation 11.53 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Social Functioning | 3.0 units on a scale | Standard Deviation 11.47 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Role Limitation Emotion | 2.8 units on a scale | Standard Deviation 12.62 |
| IV Iron Standard of Care (SOC) | Short Form Health Survey, 12-Item (SF-12) v2 Quality of Life Scores. | Role Limitation Physical | 3.9 units on a scale | Standard Deviation 9.25 |
Primary
Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores
Participants rated 14 items with 4 domains. Scores for item 1 to 3, 9 to 11 and 14 ranged from 1=extremely dissatisfied to 7=extremely satisfied. Items 5 to 8, 12, 13 ranged from 1=extremely dissatisfied to 5=not at all dissatisfied. Item 4 was scored as: 0=No, 1=Yes. Effectiveness measured as (\[{sum of item 1 to 3} - 3\]/18)\*100; if 1 question (Q) was missing: (\[{sum of item 1 to 3} -2\]/12)\*100. Side-effect measured as if item 4=No, score=100; if not then (\[{sum of item 5 to 8} -4\]/16)\*100; if 1 Q was missing: (\[{sum of item 5 to 8} -3\]/12)\*100. Convenience measured as (\[{sum of item 9 to 11} -3\]/18)\*100; if 1 Q was missing: (\[{sum of item 9 to 11} - 2\]/12)\*100. Global satisfaction as (\[{sum of item 12 to 14} -3\]/14)\*100; if item 12 or 13 was missing: (\[{sum of item 12 to 14} -2\]/10)\*100; if item 14 was missing: (\[{sum of item 12 and 13} -2\]/8)\*100. All domains had scale of 0 (no satisfaction) to 100 (best level of satisfaction), higher score equals greater satisfaction
Time frame: Baseline and Day 30
Population: Change from baseline to Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Injectafer | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Side Effects | 63.5 units on a scale | Standard Deviation 27.21 |
| Injectafer | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Overall Satisfaction | 72.6 units on a scale | Standard Deviation 25.03 |
| Injectafer | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Convenience | 78.9 units on a scale | Standard Deviation 17.31 |
| Injectafer | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Effectiveness | 69.3 units on a scale | Standard Deviation 22.38 |
| IV Iron Standard of Care (SOC) | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Convenience | 72.8 units on a scale | Standard Deviation 20 |
| IV Iron Standard of Care (SOC) | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Overall Satisfaction | 72.7 units on a scale | Standard Deviation 21.07 |
| IV Iron Standard of Care (SOC) | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Side Effects | 69.2 units on a scale | Standard Deviation 21 |
| IV Iron Standard of Care (SOC) | Treatment Satisfaction Questionnaire for Medication Version 1.4 Scores | Effectiveness | 66.5 units on a scale | Standard Deviation 21.75 |
Primary
Work Productivity and Activity Impairment Questionnaire (WPAI) Scores
The WPAI consisted of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed other reasons; 4 = hours actually worked; 5 = degree health affected productivity while working using a scale of 0 to 10, with 0 = PROBLEM had no effect on my work and 10 = PROBLEM completely prevented me from working; 6 = degree health affected productivity in regular unpaid activities using a scale of 0 to 10, with 0 = PROBLEM had no effect on my daily activities and 10 = PROBLEM completely prevented me from doing my daily activities. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time frame: Baseline and Day 30
Population: Change from baseline to Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Injectafer | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent impairment while working due to problem | -13.2 units on a scale | Standard Deviation 28.75 |
| Injectafer | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent overall work impairment due to problem | -13.4 units on a scale | Standard Deviation 31.66 |
| Injectafer | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent work time missed due to problem | -3.2 units on a scale | Standard Deviation 23.76 |
| Injectafer | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent activity impairment due to problem | -15.2 units on a scale | Standard Deviation 29.85 |
| IV Iron Standard of Care (SOC) | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent work time missed due to problem | -2.5 units on a scale | Standard Deviation 17.23 |
| IV Iron Standard of Care (SOC) | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent overall work impairment due to problem | -8.5 units on a scale | Standard Deviation 25.89 |
| IV Iron Standard of Care (SOC) | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent activity impairment due to problem | -11.5 units on a scale | Standard Deviation 29.43 |
| IV Iron Standard of Care (SOC) | Work Productivity and Activity Impairment Questionnaire (WPAI) Scores | Percent impairment while working due to problem | -8.5 units on a scale | Standard Deviation 24.44 |