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

• Sponsor: AMAG Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01114139
• Collaborator: (none)
• Enrollment: 812
• Locations: 182
• Arms: 2
• Actual Duration (Months): 28.1
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia	Drug: Ferumoxytol; Other: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 812 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Ferumoxytol for the Treatment of Iron Deficiency Anemia
• Actual Study Start Date: Jun 19, 2010
• Actual Primary Completion Date: Feb 27, 2012
• Actual Study Completion Date: Oct 22, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ferumoxytol 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; IV Ferumoxytol; Other Names: Feraheme
Placebo Comparator: 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.	Other: Placebo; IV Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria include:

1. Males and females ≥18 years of age

2. Participants with IDA defined as having:

3. Hemoglobin <10.0 g/deciliter (dL)

4. Transferrin saturation <20%

5. Participants who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used

6. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Birmingham	Alabama	United States
2	Clinical Trial Site	Mobile	Alabama	United States
3	Clinical Trial Site	Montgomery	Alabama	United States	36106
4	Clinical Trial Site	Montgomery	Alabama	United States
5	Clinical Trial Site	Green Valley	Arizona	United States
6	Clinical Trial Site	Phoenix	Arizona	United States	85032
7	Clinical Trial Site	Phoenix	Arizona	United States
8	Clinical Trial Site	Tucson	Arizona	United States	85710
9	Clinical Trial Site	Tucson	Arizona	United States
10	Clinical Trial Site	Alhambra	California	United States
11	Clinical Trial Site	Anaheim	California	United States
12	Clinical Trial Site	Bakersfield	California	United States
13	Clinical Trial Site	Buena Park	California	United States
14	Clinical Trial Site	Colton	California	United States
15	Clinical Trial Site	Fresno	California	United States
16	Clinical Trial Site	Glendale	California	United States
17	Clinical Trial Site	Laguna Hills	California	United States	92653
18	Clinical Trial Site	Laguna Hills	California	United States
19	Clinical Trial Site	Lakewood	California	United States
20	Clinical Trial Site	Los Angeles	California	United States	90036
21	Clinical Trial Site	Los Angeles	California	United States	90057
22	Clinical Trial Site	Los Angeles	California	United States
23	Clinical Trial Site	Mission Hills	California	United States
24	Clinical Trial Site	Orange	California	United States
25	Clinical Trial Site	San Diego	California	United States	92103
26	Clinical Trial Site	San Diego	California	United States	92123
27	Clinical Trial Site	San Diego	California	United States
28	Clinical Trial Site	Pueblo	Colorado	United States
29	Clinical Trial Site	Bristol	Connecticut	United States
30	Clinical Trial Site	Groton	Connecticut	United States
31	Clinical Trial Site	Newark	Delaware	United States
32	Clinical Trial Site	Boynton Beach	Florida	United States	33426
33	Clinical Trial Site	Boynton Beach	Florida	United States
34	Clinical Trial Site	Clearwater	Florida	United States	33759
35	Clinical Trial Site	Clearwater	Florida	United States
36	Clinical Trial Site	Hialeah	Florida	United States
37	Clinical Trial Site	Holiday	Florida	United States
38	Clinical Trial Site	Inverness	Florida	United States
39	Clinical Trial Site	Margate	Florida	United States
40	Clinical Trial Site	Miami Lakes	Florida	United States
41	Clinical Trial Site	Miami	Florida	United States	33126
42	Clinical Trial Site	Miami	Florida	United States	33143
43	Clinical Trial Site	Miami	Florida	United States	33144
44	Clinical Trial Site	Miami	Florida	United States	33175
45	Clinical Trial Site	Miami	Florida	United States
46	Clinical Trial Site	Naples	Florida	United States
47	Clinical Trial Site	Ocala	Florida	United States
48	Clinical Trial Site	Vero Beach	Florida	United States
49	Clinical Trial Site	Wellington	Florida	United States	33414
50	Clinical Trial Site	Wellington	Florida	United States
51	Clinical Trial Site	West Palm Beach	Florida	United States
52	Clinical Trial Site	Winter Park	Florida	United States
53	Clinical Trial Site	Zephyrhills	Florida	United States
54	Clinical Trial Site	Atlanta	Georgia	United States	30308
55	Clinical Trial Site	Atlanta	Georgia	United States	30342
56	Clinical Trial Site	Atlanta	Georgia	United States
57	Clinical Trial Site	Columbus	Georgia	United States
58	Clinical Trial Site	Decatur	Georgia	United States
59	Clinical Trial Site	Dublin	Georgia	United States
60	Clinical Trial Site	Rome	Georgia	United States
61	Clinical Trial Site	Sandy Springs	Georgia	United States
62	Clinical Trial Site	Savannah	Georgia	United States
63	Clinical Trial Site	Stockbridge	Georgia	United States
64	Clinical Trial Site	Aurora	Illinois	United States
65	Clinical Trial Site	Chicago	Illinois	United States	60611
66	Clinical Trial Site	Chicago	Illinois	United States
67	Clinical Trial Site	Evergreen Park	Illinois	United States
68	Clinical Trial Site	Skokie	Illinois	United States	60076
69	Clinical Trial Site	Skokie	Illinois	United States
70	Clinical Trial Site	Springfield	Illinois	United States
71	Clinical Trial Site	Indianapolis	Indiana	United States
72	Clinical Trial Site	Wichita	Kansas	United States
73	Clinical Trial Site	New Orleans	Louisiana	United States
74	Clinical Trial Site	Bethesda	Maryland	United States
75	Clinical Trial Site	Hollywood	Maryland	United States
76	Clinical Trial Site	Prince Frederick	Maryland	United States
77	AMAG Pharmaceuticals, Inc.	Waltham	Massachusetts	United States	02451
78	Clinical Trial Site	Bay City	Michigan	United States	48706
79	Clinical Trial Site	Bay City	Michigan	United States
80	Clinical Trial Site	Saginaw	Michigan	United States
81	Clinical Trial Site	Wyoming	Michigan	United States
82	Clinical Trial Site	Kansas City	Missouri	United States
83	Clinical Trial Site	Las Vegas	Nevada	United States
84	Clinical Trial Site	Lawrenceville	New Jersey	United States
85	Clinical Trial Site	Neptune	New Jersey	United States
86	Clinical Trial Site	Plainsboro	New Jersey	United States
87	Clinical Trial Site	Somerville	New Jersey	United States
88	Clinical Trial Site	Voorhees	New Jersey	United States
89	Clinical Trial Site	Albuquerque	New Mexico	United States
90	Clinical Trial Site	Brooklyn	New York	United States
91	Clinical Trial Site	Goshen	New York	United States
92	Clinical Trial Site	New York	New York	United States	10038
93	Clinical Trial Site	New York	New York	United States
94	Clinical Trial Site	Raleigh	North Carolina	United States
95	Clinical Trial Site	Wilmington	North Carolina	United States
96	Clinical Trial Site	Winston-Salem	North Carolina	United States
97	Clinical Trial Site	Bismarck	North Dakota	United States
98	Clinical Trial Site	Akron	Ohio	United States
99	Clinical Trial Site	Beavercreek	Ohio	United States
100	Clinical Trial Site	Canton	Ohio	United States
101	Clinical Trial Site	Carlisle	Ohio	United States
102	Clinical Trial Site	Cincinnati	Ohio	United States	45202
103	Clinical Trial Site	Cincinnati	Ohio	United States
104	Clinical Trial Site	Columbus	Ohio	United States
105	Clinical Trial Site	Dayton	Ohio	United States
106	Clinical Trial Site	Marion	Ohio	United States	43302
107	Clinical Trial Site	Marion	Ohio	United States
108	Clinical Trial Site	Mentor	Ohio	United States
109	Clinical Trial Site	Middletown	Ohio	United States
110	Clinical Trial Site	Zanesville	Ohio	United States
111	Clinical Trial Site	Norman	Oklahoma	United States
112	Clinical Trial Site	Jenkintown	Pennsylvania	United States
113	Clinical Trial Site	Levittown	Pennsylvania	United States
114	Clinical Trial Site	East Providence	Rhode Island	United States
115	Clinical Trial Site	Columbia	South Carolina	United States
116	Clinical Trial Site	Greer	South Carolina	United States
117	Clinical Trial Site	Myrtle Beach	South Carolina	United States
118	Clinical Trial Site	North Charleston	South Carolina	United States
119	Clinical Trial Site	Orangeburg	South Carolina	United States
120	Clinical Trial Site	Rapid City	South Dakota	United States
121	Clinical Trial Site	Nashville	Tennessee	United States
122	Clinical Trial Site	Arlington	Texas	United States
123	Clinical Trial Site	Dallas	Texas	United States
124	Clinical Trial Site	Houston	Texas	United States	77030
125	Clinical Trial Site	Houston	Texas	United States	77074
126	Clinical Trial Site	Houston	Texas	United States
127	Clinical Trial Site	Laredo	Texas	United States
128	Clinical Trial Site	Longview	Texas	United States
129	Clinical Trial Site	San Antonio	Texas	United States	78205
130	Clinical Trial Site	San Antonio	Texas	United States	78209
131	Clinical Trial Site	San Antonio	Texas	United States	78229
132	Clinical Trial Site	San Antonio	Texas	United States	78258
133	Clinical Trial Site	San Antonio	Texas	United States
134	Clinical Trial Site	Spring	Texas	United States
135	Clinical Trial Site	Orem	Utah	United States
136	Clinical Trial Site	Chesapeake	Virginia	United States
137	Clinical Trial Site	Norfolk	Virginia	United States
138	Clinical Trial Site	Vancouver	British Columbia	Canada
139	Clinical Trial Site	Saint John	New Brunswick	Canada
140	Clinical Trial Site	London	Ontario	Canada
141	Clinical Trial Site	Scarborough	Ontario	Canada
142	Clinical Trial Site	Thornhill	Ontario	Canada
143	Clinical Trial Site	Vaughan	Ontario	Canada
144	Clinical Trial Site	Pointe-Claire	Quebec	Canada
145	Clinical Trial Site	Békéscsaba		Hungary
146	Clinical Trial Site	Gyula		Hungary
147	Clinical Trial Site	Komárom		Hungary
148	Clinical Trial Site	Szekszárd		Hungary
149	Clinical Trial Site	Vác		Hungary
150	Clinical Trial Site	Hyderabad	Andhra Pradesh	India
151	Clinical Trial Site	Secunderabad	Andhra Pradesh	India
152	Clinical Trial Site	Visakhapatnam	Andhrapradesh	India
153	Clinical Trial Site	Guwahati	Assam	India
154	Clinical Trial Site	Bangalore	Karnataka	India	560002
155	Clinical Trial Site	Bangalore	Karnataka	India
156	Clinical Trial Site	Mangalore	Karnataka	India
157	Clinical Trial Site	Aurangabad	Maharashtra	India
158	Clinical Trial Site	Nagpur	Maharashtra	India
159	Clinical Trial Site	Nashik	Maharashtra	India
160	Clinical Trial Site	Pune	Maharashtra	India
161	Clinical Trial Site	Jaipur	Rajasthan	India	302001
162	Clinical Trial Site	Jaipur	Rajasthan	India	302013
163	Clinical Trial Site	Chennai	Tamil Nadu	India	600096
164	Clinical Trial Site	Chennai	Tamil Nadu	India
165	Clinical Trial Site	Coimbatore	Tamil Nadu	India
166	Clinical Trial Site	Madurai	Tamil Nadu	India
167	Clinical Trial Site	Lucknow	Uttar Pradesh	India	226003
168	Clinical Trial Site	Lucknow	Uttar Pradesh	India
169	Clinical Trial Site	Daugavpils		Latvia
170	Clinical Trial Site	Riga		Latvia	LV-1002
171	Clinical Trial Site	Riga		Latvia	LV-1005
172	Clinical Trial Site	Riga		Latvia	LV-1006
173	Clinical Trial Site	Riga		Latvia	LV-1010
174	Clinical Trial Site	Valmiera		Latvia	LV-4201
175	Clinical Trial Site	Ventspils		Latvia	LV-3601
176	Clinical Trial Site	Ventspils		Latvia
177	Clinical Trial Site	Białystok		Poland
178	Clinical Trial Site	Sopot		Poland
179	Clinical Trial Site	Warszawa		Poland	02-341
180	Clinical Trial Site	Warszawa		Poland	03-580
181	Clinical Trial Site	Wrocław		Poland
182	Clinical Trial Site	Zgierz		Poland

Sponsors and Collaborators

• AMAG Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Vadhan-Raj S, Strauss W, Ford D, Bernard K, Boccia R, Li J, Allen LF. Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron. Am J Hematol. 2014 Jan;89(1):7-12. doi: 10.1002/ajh.23582. Epub 2013 Sep 30.

• Responsible Party: AMAG Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01114139
• Other Study ID Numbers: AMAG-FER-IDA-301
• First Posted: Apr 30, 2010
• Last Update Posted: Apr 21, 2022
• Last Verified: Mar 1, 2022

• Keywords provided by AMAG Pharmaceuticals, Inc.: Iron deficiency anemia; Feraheme; ferumoxytol; IDA
• Additional relevant MeSH terms: Anemia; Anemia, Iron-Deficiency; Deficiency Diseases; Ferrosoferric Oxide

Study Results

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.

Arm/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	609	203
Received at Least 1 Dose of Study Drug	608	200
COMPLETED	569	187
NOT COMPLETED	40	16

Baseline Characteristics

Arm/Group Title	Ferumoxytol	Placebo	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	608	200	808
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (13.82)	46.0 (13.58)	45.1 (13.76)
Sex: Female, Male (Count of Participants)
Female	542 89.1%	178 89%	720 89.1%
Male	66 10.9%	22 11%	88 10.9%

Outcome Measures

1. Primary Outcome

Title	Participants Who Achieved A ≥2.0 g/dL Increase In Hemoglobin At Any Time From Baseline To Week 5
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Measure Participants	608	200
Up to Week 2	252 41.4%	5 2.5%
Up to Week 3	386 63.5%	7 3.5%
Up to Week 4	460 75.7%	8 4%
Up to Week 5	493 81.1%	11 5.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ferumoxytol, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	The 95% confidence interval was calculated using the large sample assumption.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The p-value is the result of the Cochran-Mantel-Haenszel test, adjusted for Baseline hemoglobin level and underlying condition.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	75.59
	Confidence Interval	(2-Sided) 95%; 71.15 to 80.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	The treatment difference (ferumoxytol - placebo) was expressed as a percentage.

2. Secondary Outcome

Title	Mean Change In Hemoglobin From Baseline To Week 5
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Measure Participants	608	200
Mean (Standard Deviation) [g/dL]	2.6 (1.52)	0.1 (0.89)

3. Secondary Outcome

Title	Participants Achieving A Hemoglobin Level ≥12.0 g/dL At Any Time From Baseline To Week 5
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population: Any randomized participant who had any exposure to study drug (ferumoxytol or placebo) and was based upon randomized treatment assignment.

Arm/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Measure Participants	608	200
Up to Week 2	33 5.4%	3 1.5%
Up to Week 3	131 21.5%	5 2.5%
Up to Week 4	240 39.5%	5 2.5%
Up to Week 5	307 50.5%	6 3%

4. Secondary Outcome

Title	Mean Change In TSAT From Baseline To Week 5
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Measure Participants	608	200
Mean (Standard Deviation) [percentage of saturation]	11.4 (15.06)	0.4 (5.81)

5. Secondary Outcome

Title	Mean Change In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline To Week 5
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Measure Participants	608	200
Mean (Standard Deviation) [units on a scale]	11.7 (11.73)	6.8 (9.51)

6. Secondary Outcome

Title	Time To Hemoglobin Increase Of ≥2.0 g/dL Or A Hemoglobin Value Of ≥12.0 g/dL From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ferumoxytol	Placebo
Arm/Group Description	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.	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.
Measure Participants	608	200
Mean (Inter-Quartile Range) [Days]	23.5	42.5

Adverse Events

Arm/Group Title	Ferumoxytol		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Ferumoxytol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ferumoxytol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/608 (2.6%)		6/200 (3%)
Blood and lymphatic system disorders
Anaemia	1/608 (0.2%)		3/200 (1.5%)
Cardiac disorders
Supraventricular Tachycardia	1/608 (0.2%)		0/200 (0%)
Gastrointestinal disorders
Colitis Ulcerative	1/608 (0.2%)		0/200 (0%)
Gastrointestinal Haemorrhage	1/608 (0.2%)		0/200 (0%)
Vomiting	1/608 (0.2%)		0/200 (0%)
General disorders
Chest Pain	1/608 (0.2%)		0/200 (0%)
Disease Progression	1/608 (0.2%)		0/200 (0%)
Immune system disorders
Anaphylactic Reaction	1/608 (0.2%)		0/200 (0%)
Hypersensitivity	3/608 (0.5%)		0/200 (0%)
Infections and infestations
Gastroenteritis	1/608 (0.2%)		0/200 (0%)
Gastroenteritis Viral	1/608 (0.2%)		0/200 (0%)
Lobar Pneumonia	1/608 (0.2%)		0/200 (0%)
Septic Shock	1/608 (0.2%)		0/200 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	1/608 (0.2%)		0/200 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion	1/608 (0.2%)		0/200 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant	0/608 (0%)		1/200 (0.5%)
Small Intestine Carcinoma	1/608 (0.2%)		0/200 (0%)
Nervous system disorders
Convulsion	0/608 (0%)		1/200 (0.5%)
Hypoaesthesia	1/608 (0.2%)		0/200 (0%)
Renal and urinary disorders
Nephrolithiasis	1/608 (0.2%)		0/200 (0%)
Reproductive system and breast disorders
Dysfunctional Uterine Bleeding	0/542 (0%)		1/178 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/608 (0.2%)		0/200 (0%)
Epistaxis	1/608 (0.2%)		0/200 (0%)
Other (Not Including Serious) Adverse Events
	Ferumoxytol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	198/608 (32.6%)		56/200 (28%)
Gastrointestinal disorders
Abdominal Pain	11/608 (1.8%)		5/200 (2.5%)
Abdominal Pain Upper	7/608 (1.2%)		1/200 (0.5%)
Constipation	10/608 (1.6%)		3/200 (1.5%)
Diarrhoea	17/608 (2.8%)		6/200 (3%)
Nausea	28/608 (4.6%)		5/200 (2.5%)
Toothache	5/608 (0.8%)		3/200 (1.5%)
Vomiting	12/608 (2%)		2/200 (1%)
General disorders
Fatigue	12/608 (2%)		3/200 (1.5%)
Oedema Peripheral	10/608 (1.6%)		1/200 (0.5%)
Pyrexia	7/608 (1.2%)		1/200 (0.5%)
Infections and infestations
Nasopharyngitis	16/608 (2.6%)		4/200 (2%)
Upper Respiratory Tract Infection	8/608 (1.3%)		2/200 (1%)
Urinary Tract Infection	17/608 (2.8%)		6/200 (3%)
Injury, poisoning and procedural complications
Skin Laceration	0/608 (0%)		3/200 (1.5%)
Metabolism and nutrition disorders
Hypokalaemia	9/608 (1.5%)		0/200 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/608 (1.5%)		5/200 (2.5%)
Back Pain	10/608 (1.6%)		2/200 (1%)
Muscle Spasms	7/608 (1.2%)		2/200 (1%)
Pain in Extremity	7/608 (1.2%)		1/200 (0.5%)
Nervous system disorders
Dizziness	24/608 (3.9%)		7/200 (3.5%)
Dysgeusia	9/608 (1.5%)		1/200 (0.5%)
Headache	35/608 (5.8%)		12/200 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	7/608 (1.2%)		1/200 (0.5%)
Dyspnoea	9/608 (1.5%)		4/200 (2%)
Skin and subcutaneous tissue disorders
Pruritus	3/608 (0.5%)		3/200 (1.5%)
Rash	12/608 (2%)		0/200 (0%)
Vascular disorders
Hypertension	9/608 (1.5%)		0/200 (0%)
Hypotension	8/608 (1.3%)		1/200 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.