Trial Outcomes & Findings for A Trial Comparing Ferumoxytol With Placebo for the Treatment of Iron Deficiency Anemia (NCT NCT01114139)

NCT ID: NCT01114139

Last Updated: 2022-04-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

812 participants

Primary outcome timeframe

Baseline (Day 1) through Week 5

Results posted on

2022-04-21

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Ferumoxytol
Participants received a total of 2 doses of intravenous (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 g.
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.
Overall Study
STARTED
609
203
Overall Study
Received at Least 1 Dose of Study Drug
608
200
Overall Study
COMPLETED
569
187
Overall Study
NOT COMPLETED
40
16

Reasons for withdrawal

Reasons for withdrawal
Measure
Ferumoxytol
Participants received a total of 2 doses of intravenous (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 g.
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.
Overall Study
Adverse Event
3
2
Overall Study
Lost to Follow-up
15
3
Overall Study
Withdrawal by Subject
17
6
Overall Study
Other-Missed 1 visit
1
0
Overall Study
Other-Protocol Violation
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-Withdrew prior to receiving dose
1
3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
Total
n=808 Participants
Total of all reporting groups
Age, Continuous
44.8 years
STANDARD_DEVIATION 13.82 • n=5 Participants
46.0 years
STANDARD_DEVIATION 13.58 • n=7 Participants
45.1 years
STANDARD_DEVIATION 13.76 • n=5 Participants
Sex: Female, Male
Female
542 Participants
n=5 Participants
178 Participants
n=7 Participants
720 Participants
n=5 Participants
Sex: Female, Male
Male
66 Participants
n=5 Participants
22 Participants
n=7 Participants
88 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
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
5 Participants
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
7 Participants
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
8 Participants
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
11 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
Mean Change In Hemoglobin From Baseline To Week 5
2.6 g/dL
Standard Deviation 1.52
0.1 g/dL
Standard Deviation 0.89

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Up to Week 2
33 Participants
3 Participants
Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Up to Week 3
131 Participants
5 Participants
Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Up to Week 4
240 Participants
5 Participants
Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Up to Week 5
307 Participants
6 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
Mean Change In TSAT From Baseline To Week 5
11.4 percentage of saturation
Standard Deviation 15.06
0.4 percentage of saturation
Standard Deviation 5.81

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
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
6.8 units on a scale
Standard Deviation 9.51

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Ferumoxytol
n=608 Participants
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.
Placebo
n=200 Participants
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.
Time To Hemoglobin Increase Of ≥2.0 g/dL Or A Hemoglobin Value Of ≥12.0 g/dL From Baseline
23.5 Days
Interval 15.0 to 29.0
42.5 Days
Interval 44.0 to
Insufficient number of participants with events.

Adverse Events

Ferumoxytol

Serious events: 16 serious events
Other events: 198 other events
Deaths: 0 deaths

Placebo

Serious events: 6 serious events
Other events: 56 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ferumoxytol
n=608 participants at risk
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.
Placebo
n=200 participants at risk
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.
Blood and lymphatic system disorders
Anaemia
0.16%
1/608
1.5%
3/200
Cardiac disorders
Supraventricular Tachycardia
0.16%
1/608
0.00%
0/200
Gastrointestinal disorders
Colitis Ulcerative
0.16%
1/608
0.00%
0/200
Gastrointestinal disorders
Gastrointestinal Haemorrhage
0.16%
1/608
0.00%
0/200
Gastrointestinal disorders
Vomiting
0.16%
1/608
0.00%
0/200
General disorders
Chest Pain
0.16%
1/608
0.00%
0/200
General disorders
Disease Progression
0.16%
1/608
0.00%
0/200
Immune system disorders
Anaphylactic Reaction
0.16%
1/608
0.00%
0/200
Immune system disorders
Hypersensitivity
0.49%
3/608
0.00%
0/200
Infections and infestations
Gastroenteritis
0.16%
1/608
0.00%
0/200
Infections and infestations
Gastroenteritis Viral
0.16%
1/608
0.00%
0/200
Infections and infestations
Lobar Pneumonia
0.16%
1/608
0.00%
0/200
Infections and infestations
Septic Shock
0.16%
1/608
0.00%
0/200
Metabolism and nutrition disorders
Hyperkalaemia
0.16%
1/608
0.00%
0/200
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
0.16%
1/608
0.00%
0/200
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant
0.00%
0/608
0.50%
1/200
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small Intestine Carcinoma
0.16%
1/608
0.00%
0/200
Nervous system disorders
Convulsion
0.00%
0/608
0.50%
1/200
Nervous system disorders
Hypoaesthesia
0.16%
1/608
0.00%
0/200
Renal and urinary disorders
Nephrolithiasis
0.16%
1/608
0.00%
0/200
Reproductive system and breast disorders
Dysfunctional Uterine Bleeding
0.00%
0/542
0.56%
1/178
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.16%
1/608
0.00%
0/200
Respiratory, thoracic and mediastinal disorders
Epistaxis
0.16%
1/608
0.00%
0/200

Other adverse events

Other adverse events
Measure
Ferumoxytol
n=608 participants at risk
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.
Placebo
n=200 participants at risk
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.
Gastrointestinal disorders
Abdominal Pain
1.8%
11/608
2.5%
5/200
Gastrointestinal disorders
Abdominal Pain Upper
1.2%
7/608
0.50%
1/200
Gastrointestinal disorders
Constipation
1.6%
10/608
1.5%
3/200
Gastrointestinal disorders
Diarrhoea
2.8%
17/608
3.0%
6/200
Gastrointestinal disorders
Nausea
4.6%
28/608
2.5%
5/200
Gastrointestinal disorders
Toothache
0.82%
5/608
1.5%
3/200
Gastrointestinal disorders
Vomiting
2.0%
12/608
1.0%
2/200
General disorders
Fatigue
2.0%
12/608
1.5%
3/200
General disorders
Oedema Peripheral
1.6%
10/608
0.50%
1/200
General disorders
Pyrexia
1.2%
7/608
0.50%
1/200
Infections and infestations
Nasopharyngitis
2.6%
16/608
2.0%
4/200
Infections and infestations
Upper Respiratory Tract Infection
1.3%
8/608
1.0%
2/200
Infections and infestations
Urinary Tract Infection
2.8%
17/608
3.0%
6/200
Injury, poisoning and procedural complications
Skin Laceration
0.00%
0/608
1.5%
3/200
Metabolism and nutrition disorders
Hypokalaemia
1.5%
9/608
0.00%
0/200
Musculoskeletal and connective tissue disorders
Arthralgia
1.5%
9/608
2.5%
5/200
Musculoskeletal and connective tissue disorders
Back Pain
1.6%
10/608
1.0%
2/200
Musculoskeletal and connective tissue disorders
Muscle Spasms
1.2%
7/608
1.0%
2/200
Musculoskeletal and connective tissue disorders
Pain in Extremity
1.2%
7/608
0.50%
1/200
Nervous system disorders
Dizziness
3.9%
24/608
3.5%
7/200
Nervous system disorders
Dysgeusia
1.5%
9/608
0.50%
1/200
Nervous system disorders
Headache
5.8%
35/608
6.0%
12/200
Respiratory, thoracic and mediastinal disorders
Cough
1.2%
7/608
0.50%
1/200
Respiratory, thoracic and mediastinal disorders
Dyspnoea
1.5%
9/608
2.0%
4/200
Skin and subcutaneous tissue disorders
Pruritus
0.49%
3/608
1.5%
3/200
Skin and subcutaneous tissue disorders
Rash
2.0%
12/608
0.00%
0/200
Vascular disorders
Hypertension
1.5%
9/608
0.00%
0/200
Vascular disorders
Hypotension
1.3%
8/608
0.50%
1/200

Additional Information

Medical Information

AMAG Pharmaceuticals, Inc.

Results disclosure agreements

  • Principal investigator is a sponsor employee If no multi-site publication within 18 months after Study has been completed or terminated at all Study sites, and all data have been received by Sponsor, Site, and Site Management Organization (SMO) shall have the right to publish its results from the Study for non-commercial purposes, if submitted to Sponsor for review 60 days prior to submission of publication. Publication must remove all confidential information and may be delayed by up to 180 days to allow Sponsor to protect its interests.
  • Publication restrictions are in place

Restriction type: OTHER