A Trial Comparing Ferumoxytol With Placebo for the Treatment of Iron Deficiency Anemia

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of intravenous (IV) ferumoxytol compared with placebo for the treatment of iron deficiency anemia (IDA).

Detailed Description
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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.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Ferumoxytol for the Treatment of Iron Deficiency Anemia

Conditions
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Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Ferumoxytol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria include: Males and females ≥18 years of age Participants with IDA defined as having: Hemoglobin <10.0 g/deciliter (dL) Transferrin saturation <20% Participants who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used 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: History of allergy to IV iron Allergy to two or more classes of drugs Participants on dialysis or with an estimated glomerular filtration rate <30 mL/minute/1.73 m^2 Female participants who are pregnant, intend to become pregnant, are breastfeeding, within 2 weeks postpartum, or have a positive serum/urine pregnancy test Hemoglobin ≤7.0 g/dL Serum ferritin >600 nanograms/mL

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferumoxytol<br>Participants received a total of 2 doses of IV ferumoxytol 510 milligrams (mg) (17 milliliters [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 grams (g). | Drug: Ferumoxytol<br>* IV Ferumoxytol<br>* Other names: Feraheme;|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br>* IV Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 1) through Week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 1), Week 5 | 
| 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. | Baseline (Day 1) through Week 5 | 
| 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. | Baseline (Day 1), Week 5 | 
| 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. | Baseline (Day 1), Week 5 | 
| 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. | From Baseline (Day 1) up to Week 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron deficiency anemia, Feraheme, ferumoxytol, IDA