Iron Deficiency Anemia
Conditions
Keywords
Iron deficiency anemia, Feraheme, ferumoxytol, IDA
Brief summary
To evaluate the efficacy and safety of intravenous (IV) ferumoxytol compared with placebo for the treatment of iron deficiency anemia (IDA).
Detailed description
This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical study evaluated the safety and efficacy of ferumoxytol compared with placebo for the treatment of IDA, specifically in adult patients with IDA who have a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. The effect of ferumoxytol on hemoglobin, iron parameters and patient reported outcomes (PROs) compared with placebo was evaluated. Investigators were blinded to key laboratory parameters that could potentially unblind the treatment arms of the study, eg, hemoglobin \[Hgb\], hematocrit \[Hct\], iron, ferritin, total iron binding capacity \[TIBC\], and transferrin saturation \[TSAT\], and neither the Investigators nor the subjects were aware of their treatment assignment, hemoglobin or other laboratory values.
Interventions
DRUGFerumoxytol
IV Ferumoxytol
OTHERPlacebo
IV Placebo
Sponsors
AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria include: 1. Males and females ≥18 years of age 2. Participants with IDA defined as having: 1. Hemoglobin \<10.0 g/deciliter (dL) 2. Transferrin saturation \<20% 3. Participants who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used 4. Female participants of childbearing potential who are sexually active must be on an effective method of birth control for at least 1 month prior to screening and agree to remain on birth control until completion of participation in the study Key
Exclusion criteria
include: 1. History of allergy to IV iron 2. Allergy to two or more classes of drugs 3. Participants on dialysis or with an estimated glomerular filtration rate \<30 mL/minute/1.73 m\^2 4. Female participants who are pregnant, intend to become pregnant, are breastfeeding, within 2 weeks postpartum, or have a positive serum/urine pregnancy test 5. Hemoglobin ≤7.0 g/dL 6. Serum ferritin \>600 nanograms/mL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Baseline (Day 1) through Week 5 | Participants who achieved a ≥2.0 g/dL increase in hemoglobin at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants with no post-Baseline hemoglobin values were classified as not achieving a ≥2.0 g/dL increase. Statistical analysis was performed for data up to Week 5 only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change In Hemoglobin From Baseline To Week 5 | Baseline (Day 1), Week 5 | Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 hemoglobin value was missing, the change from Baseline was imputed to be zero. Participants without any post-Baseline hemoglobin values were treated as non-responders. |
| Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Baseline (Day 1) through Week 5 | Participants who achieved a ≥12.0 g/dL hemoglobin level at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants without any post-Baseline hemoglobin values were treated as non-responders. |
| Mean Change In TSAT From Baseline To Week 5 | Baseline (Day 1), Week 5 | Mean change in TSAT from Baseline to Week 5 was calculated for each participant as: TSAT Change = TSAT (Week 5) - TSAT (Baseline). TSAT, measured as a percentage, was part of the iron panel laboratory evaluations. Of the transferrin available to bind iron, this value indicates how much serum iron is bound. For example, a value of 20% means that 20% of iron-binding sites of transferrin are being occupied by iron. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 TSAT value was missing, the change from Baseline was imputed to be zero. |
| Mean Change In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5 | Baseline (Day 1), Week 5 | The FACIT-Fatigue questionnaire is a 13-item questionnaire designed and validated to specifically assess the presence and impact of treatment on fatigue and related symptoms, such as tiredness, on health-related quality of life in anemic participants with cancer. The questionnaire has 13 items, each measured on a 4-point Likert scale. Scoring ranges from 0 (the most fatigued) to 52 (the least fatigued) points, with higher scores representing better functioning or less fatigue. Mean change in FACIT-Fatigue Score from Baseline to Week 5 was calculated for each participant as: FACIT-Fatigue Score Change = FACIT-Fatigue Score (Week 5) - FACIT-Fatigue Score (Baseline). Baseline was defined as the Day 1 value (prior to first dose of study drug).The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 FACIT-Fatigue Score value was missing, the change from Baseline was imputed to be zero. |
| Time To Hemoglobin Increase Of ≥2.0 g/dL Or A Hemoglobin Value Of ≥12.0 g/dL From Baseline | From Baseline (Day 1) up to Week 5 | The time to hemoglobin increase of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL was defined as the days from Baseline (Day 1) to the first time the participant had an increase in hemoglobin of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL, and was calculated using a Kaplan-Meier curve. Participants who did not have a hemoglobin increase of ≥2.0 g/dL or to a hemoglobin level ≥12.0 g/dL were censored at their last visit day. Participants without any post-Baseline study visits were not included. |
Countries
Canada, Hungary, India, Latvia, Poland, United States
Participant flow
Recruitment details
The study was open to enrollment for adult participants with iron deficiency anemia (IDA), defined as hemoglobin \<10.0 gram (g)/deciliter (dL) and transferrin saturation (TSAT) \<20%, and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used.
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol Participants received a total of 2 doses of IV ferumoxytol 510 mg (17 mL). The first IV 510 mg dose was administered on Day 1 (Baseline) and second dose 2 to 8 (5±3) days after the first dose, for a total cumulative dose of 1.02 g. | 608 |
| Placebo Participants received a total of 2 doses of IV saline (17 mL). The first IV dose was administered on Day 1 (Baseline) and second dose 2 to 8 (5±3) days after the first dose. | 200 |
| Total | 808 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lost to Follow-up | 15 | 3 |
| Overall Study | Other-Missed 1 visit | 1 | 0 |
| Overall Study | Other-Out of window for study drug dose | 1 | 0 |
| Overall Study | Other-Participant falsified records | 0 | 1 |
| Overall Study | Other-Participant went on hospice | 0 | 1 |
| Overall Study | Other-Physician changed treatment | 1 | 0 |
| Overall Study | Other-Protocol Violation | 1 | 0 |
| Overall Study | Other-Withdrew prior to receiving dose | 1 | 3 |
| Overall Study | Withdrawal by Subject | 17 | 6 |
Baseline characteristics
| Characteristic | Ferumoxytol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 13.82 | 46.0 years STANDARD_DEVIATION 13.58 | 45.1 years STANDARD_DEVIATION 13.76 |
| Sex: Female, Male Female | 542 Participants | 178 Participants | 720 Participants |
| Sex: Female, Male Male | 66 Participants | 22 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 198 / 608 | 56 / 200 |
| serious Total, serious adverse events | 16 / 608 | 6 / 200 |
Outcome results
Primary
Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5
Participants who achieved a ≥2.0 g/dL increase in hemoglobin at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants with no post-Baseline hemoglobin values were classified as not achieving a ≥2.0 g/dL increase. Statistical analysis was performed for data up to Week 5 only.
Time frame: Baseline (Day 1) through Week 5
Population: Intent-To-Treat (ITT) Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 2 | 252 Participants |
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 3 | 386 Participants |
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 4 | 460 Participants |
| Ferumoxytol | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 5 | 493 Participants |
| Placebo | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 5 | 11 Participants |
| Placebo | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 2 | 5 Participants |
| Placebo | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 4 | 8 Participants |
| Placebo | Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5 | Up to Week 3 | 7 Participants |
Comparison: Participants who achieved a ≥2.0 g/dL increase in hemoglobin from Baseline up to Week 5 were analyzed. Statistical comparison was performed for data up to Week 5 only. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information.p-value: <0.000195% CI: [71.15, 80.02]Cochran-Mantel-Haenszel
Secondary
Mean Change In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5
The FACIT-Fatigue questionnaire is a 13-item questionnaire designed and validated to specifically assess the presence and impact of treatment on fatigue and related symptoms, such as tiredness, on health-related quality of life in anemic participants with cancer. The questionnaire has 13 items, each measured on a 4-point Likert scale. Scoring ranges from 0 (the most fatigued) to 52 (the least fatigued) points, with higher scores representing better functioning or less fatigue. Mean change in FACIT-Fatigue Score from Baseline to Week 5 was calculated for each participant as: FACIT-Fatigue Score Change = FACIT-Fatigue Score (Week 5) - FACIT-Fatigue Score (Baseline). Baseline was defined as the Day 1 value (prior to first dose of study drug).The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 FACIT-Fatigue Score value was missing, the change from Baseline was imputed to be zero.
Time frame: Baseline (Day 1), Week 5
Population: Intent-To-Treat (ITT) Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5 | 11.7 units on a scale | Standard Deviation 11.73 |
| Placebo | Mean Change In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5 | 6.8 units on a scale | Standard Deviation 9.51 |
Secondary
Mean Change In Hemoglobin From Baseline To Week 5
Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 hemoglobin value was missing, the change from Baseline was imputed to be zero. Participants without any post-Baseline hemoglobin values were treated as non-responders.
Time frame: Baseline (Day 1), Week 5
Population: Intent-To-Treat (ITT) Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In Hemoglobin From Baseline To Week 5 | 2.6 g/dL | Standard Deviation 1.52 |
| Placebo | Mean Change In Hemoglobin From Baseline To Week 5 | 0.1 g/dL | Standard Deviation 0.89 |
Secondary
Mean Change In TSAT From Baseline To Week 5
Mean change in TSAT from Baseline to Week 5 was calculated for each participant as: TSAT Change = TSAT (Week 5) - TSAT (Baseline). TSAT, measured as a percentage, was part of the iron panel laboratory evaluations. Of the transferrin available to bind iron, this value indicates how much serum iron is bound. For example, a value of 20% means that 20% of iron-binding sites of transferrin are being occupied by iron. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. If the Week 5 TSAT value was missing, the change from Baseline was imputed to be zero.
Time frame: Baseline (Day 1), Week 5
Population: Intent-To-Treat (ITT) Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Mean Change In TSAT From Baseline To Week 5 | 11.4 percentage of saturation | Standard Deviation 15.06 |
| Placebo | Mean Change In TSAT From Baseline To Week 5 | 0.4 percentage of saturation | Standard Deviation 5.81 |
Secondary
Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Participants who achieved a ≥12.0 g/dL hemoglobin level at any time from Baseline up to Week 5 are presented. Increase in hemoglobin at any time from Baseline up to Week 5 was calculated for each participant based on: Hemoglobin Change = Hemoglobin (Week X) - Hemoglobin (Baseline), where Week X was any post-Baseline visit up to and including Week 5. Baseline was defined as the Day 1 value (prior to injection of study drug). The screening or most recent value prior to Day 1 was used for any participant with missing Day 1 information. Participants without any post-Baseline hemoglobin values were treated as non-responders.
Time frame: Baseline (Day 1) through Week 5
Population: ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 2 | 33 Participants |
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 3 | 131 Participants |
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 4 | 240 Participants |
| Ferumoxytol | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 5 | 307 Participants |
| Placebo | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 5 | 6 Participants |
| Placebo | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 2 | 3 Participants |
| Placebo | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 4 | 5 Participants |
| Placebo | Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5 | Up to Week 3 | 5 Participants |
Secondary
Time To Hemoglobin Increase Of ≥2.0 g/dL Or A Hemoglobin Value Of ≥12.0 g/dL From Baseline
The time to hemoglobin increase of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL was defined as the days from Baseline (Day 1) to the first time the participant had an increase in hemoglobin of ≥2.0 g/dL or hemoglobin value of ≥12.0 g/dL, and was calculated using a Kaplan-Meier curve. Participants who did not have a hemoglobin increase of ≥2.0 g/dL or to a hemoglobin level ≥12.0 g/dL were censored at their last visit day. Participants without any post-Baseline study visits were not included.
Time frame: From Baseline (Day 1) up to Week 5
Population: Intent-To-Treat (ITT) Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ferumoxytol | Time To Hemoglobin Increase Of ≥2.0 g/dL Or A Hemoglobin Value Of ≥12.0 g/dL From Baseline | 23.5 Days |
| Placebo | Time To Hemoglobin Increase Of ≥2.0 g/dL Or A Hemoglobin Value Of ≥12.0 g/dL From Baseline | 42.5 Days |