Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase III Safety Study of Ferumoxytol Compared to Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (IDA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02694978
Recruitment Status : Completed
First Posted : March 1, 2016
Results First Posted : June 11, 2018
Last Update Posted : June 11, 2018
Sponsor:
Information provided by (Responsible Party):
AMAG Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Iron Deficiency Anemia
Interventions Drug: Ferumoxytol
Drug: FCM
Enrollment 2014
Recruitment Details Participants with iron deficiency anemia (IDA), <12.0 grams (g) per deciliter (dL) for females and <14.0 g/dL for males within 60 days of dosing and transferrin saturation (TSAT) <20% or Ferritin ≤100 nanograms (ng) per milliliter (mL) within 60 days of dosing and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used.
Pre-assignment Details  
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM)
Hide Arm/Group Description Participants received an IV infusion of ferumoxytol 510 milligram (mg) diluted (17 milliliter [mL]) in 233 mL 0.9% sodium chloride injection, United States Pharmacopeia (USP) (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g. Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g.
Period Title: Overall Study
Started 1006 1008
Received at Least 1 Dose of Study Drug 997 1000
Completed [1] 935 948
Not Completed 71 60
Reason Not Completed
Adverse Event             10             9
Withdrawal by Subject             22             19
Lost to Follow-up             14             17
Death             4             1
Other-Decision of Participant             6             1
Other-Investigator’s decision             1             0
Other-Unable to be reached             0             1
Other-Protocol noncompliant             2             1
Other-Personal reasons             3             3
Other-Withdrew prior to dosing             9             8
[1]
Completed=received at least 1 dose of study drug and returned for final study visit (Week 5).
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM) Total
Hide Arm/Group Description Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g. Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g. Total of all reporting groups
Overall Number of Baseline Participants 997 1000 1997
Hide Baseline Analysis Population Description
The safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 997 participants 1000 participants 1997 participants
55.6  (17.30) 54.8  (17.02) 55.2  (17.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 997 participants 1000 participants 1997 participants
Female
743
  74.5%
776
  77.6%
1519
  76.1%
Male
254
  25.5%
224
  22.4%
478
  23.9%
1.Primary Outcome
Title Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension
Hide Description

All IV iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Signs and symptoms potentially representing hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee (CEC). Hypotension is defined as a >30% drop in systolic blood pressure from baseline or decrease of >20 mmHg for systolic blood pressure.

Statistical analysis was only performed on composite data. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time Frame Day 1 (after first dosing) through Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM)
Hide Arm/Group Description:
Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g.
Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g.
Overall Number of Participants Analyzed 997 1000
Measure Type: Count of Participants
Unit of Measure: Participants
Moderate hypersensitivity reaction
3
   0.3%
6
   0.6%
Severe hypersensitivity reaction
1
   0.1%
0
   0.0%
Anaphylaxis
0
   0.0%
0
   0.0%
Moderate hypotension
2
   0.2%
1
   0.1%
Severe hypotension
0
   0.0%
0
   0.0%
Any TE moderate to severe hypersensitivity rxn
6
   0.6%
7
   0.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ferumoxytol, Ferric Carboxymaltose (FCM)
Comments Statistical analysis was only performed on composite reaction data (that is, the "Any TE moderate to severe hypersensitivity rxn" row in the data table).
Type of Statistical Test Non-Inferiority
Comments The non-inferiority margin of 2.64% was used for the primary endpoint statistical analysis.
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Wald
Comments The p-value was calculated using the Wald large sample assumption.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.80 to 0.61
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Participants With Moderate To Severe Hypersensitivity Reactions, Including Anaphylaxis, Serious Cardiovascular Events, And Death
Hide Description

All IV iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Signs and symptoms potentially representing hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee (CEC).

A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time Frame Day 1 (after first dosing) through Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM)
Hide Arm/Group Description:
Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g.
Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g.
Overall Number of Participants Analyzed 997 1000
Measure Type: Count of Participants
Unit of Measure: Participants
Moderate hypersensitivity reaction
3
   0.3%
6
   0.6%
Severe hypersensitivity reaction
1
   0.1%
0
   0.0%
Anaphylaxis
0
   0.0%
0
   0.0%
Serious cardiovascular event
6
   0.6%
13
   1.3%
Death
4
   0.4%
2
   0.2%
Any moderate to severe hypersensitivity rxn
13
   1.3%
20
   2.0%
3.Secondary Outcome
Title Mean Change In Hemoglobin From Baseline To Week 5
Hide Description Mean change in hemoglobin from Baseline to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) – Hemoglobin (Baseline). 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.
Time Frame Baseline (Day 1), Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: any randomized participant who had any exposure to study drug, based on randomized treatment assignment.
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM)
Hide Arm/Group Description:
Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g.
Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g.
Overall Number of Participants Analyzed 997 1000
Mean (Standard Deviation)
Unit of Measure: g/dL
1.38  (1.351) 1.63  (1.535)
4.Secondary Outcome
Title Mean Change In Hemoglobin Per Gram Of Iron Administered From Baseline To Week 5
Hide Description Mean change in hemoglobin per g of iron administered from Baseline (Day 1) to Week 5 was calculated for each participant as: Hemoglobin Change = Hemoglobin (Week 5) – Hemoglobin (Baseline). 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.
Time Frame Baseline (Day 1), Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: any randomized participant who had any exposure to study drug, based on randomized treatment assignment.
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM)
Hide Arm/Group Description:
Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g.
Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g.
Overall Number of Participants Analyzed 997 1000
Mean (Standard Deviation)
Unit of Measure: g/dL
1.35  (1.353) 1.10  (1.050)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ferumoxytol Ferric Carboxymaltose (FCM)
Hide Arm/Group Description Participants received an IV infusion of ferumoxytol 510 mg diluted (17 mL) in 233 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.020 g. Participants received an IV infusion of FCM 750 mg diluted (15 mL) in 235 mL 0.9% sodium chloride injection, USP (normal saline) (final volume 250 mL) over at least 15 minutes with a second dose 7-8 days after the first dose, for a total cumulative dose of 1.500 g.
All-Cause Mortality
Ferumoxytol Ferric Carboxymaltose (FCM)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ferumoxytol Ferric Carboxymaltose (FCM)
Affected / at Risk (%) Affected / at Risk (%)
Total   36/997 (3.61%)   35/1000 (3.50%) 
Blood and lymphatic system disorders     
Haemorrhagic anaemia  2/997 (0.20%)  0/1000 (0.00%) 
Anaemia vitamin B12 deficiency  1/997 (0.10%)  0/1000 (0.00%) 
Cardiac disorders     
Cardiac failure congestive  1/997 (0.10%)  3/1000 (0.30%) 
Cardiorespiratory arrest  1/997 (0.10%)  0/1000 (0.00%) 
Left ventricular failure  1/997 (0.10%)  0/1000 (0.00%) 
Angina pectoris  0/997 (0.00%)  2/1000 (0.20%) 
Atrial fibrillation  0/997 (0.00%)  2/1000 (0.20%) 
Cardiac failure  0/997 (0.00%)  1/1000 (0.10%) 
Cardiac failure chronic  0/997 (0.00%)  1/1000 (0.10%) 
Acute myocardial infarction  0/997 (0.00%)  1/1000 (0.10%) 
Gastrointestinal disorders     
Gastric ulcer haemorrhage  1/997 (0.10%)  1/1000 (0.10%) 
Abdominal pain  1/997 (0.10%)  0/1000 (0.00%) 
Ascites  1/997 (0.10%)  0/1000 (0.00%) 
Pancreatitis acute  1/997 (0.10%)  0/1000 (0.00%) 
Gastric haemorrhage  0/997 (0.00%)  1/1000 (0.10%) 
Gastroduodenal ulcer  0/997 (0.00%)  1/1000 (0.10%) 
Gastrointestinal haemorrhage  0/997 (0.00%)  1/1000 (0.10%) 
Impaired gastric emptying  0/997 (0.00%)  1/1000 (0.10%) 
Pancreatitis chronic  0/997 (0.00%)  1/1000 (0.10%) 
General disorders     
Chest pain  0/997 (0.00%)  1/1000 (0.10%) 
Hepatobiliary disorders     
Hepatitis acute  0/997 (0.00%)  1/1000 (0.10%) 
Immune system disorders     
Anaphylactic reaction  1/997 (0.10%)  0/1000 (0.00%) 
Infections and infestations     
Gastroenteritis  3/997 (0.30%)  1/1000 (0.10%) 
Pneumonia  2/997 (0.20%)  0/1000 (0.00%) 
Osteomyelitis chronic  1/997 (0.10%)  0/1000 (0.00%) 
Joint abscess  1/997 (0.10%)  0/1000 (0.00%) 
Anal abscess  1/997 (0.10%)  0/1000 (0.00%) 
Cellulitis  1/997 (0.10%)  1/1000 (0.10%) 
Sepsis  1/997 (0.10%)  0/1000 (0.00%) 
Sepsis syndrome  1/997 (0.10%)  0/1000 (0.00%) 
Osteomyelitis  0/997 (0.00%)  1/1000 (0.10%) 
Injury, poisoning and procedural complications     
Anastomotic ulcer  1/997 (0.10%)  0/1000 (0.00%) 
Intentional overdose  1/997 (0.10%)  0/1000 (0.00%) 
Fall  0/997 (0.00%)  1/1000 (0.10%) 
Post-procedural haemorrhage  0/997 (0.00%)  1/1000 (0.10%) 
Wound dehiscence  0/997 (0.00%)  1/1000 (0.10%) 
Metabolism and nutrition disorders     
Fluid overload  1/997 (0.10%)  1/1000 (0.10%) 
Hyperkalaemia  1/997 (0.10%)  0/1000 (0.00%) 
Hypokalaemia  1/997 (0.10%)  0/1000 (0.00%) 
Musculoskeletal and connective tissue disorders     
Haemarthrosis  1/997 (0.10%)  0/1000 (0.00%) 
Arthritis  0/997 (0.00%)  1/1000 (0.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1/997 (0.10%)  1/1000 (0.10%) 
Bladder cancer  0/997 (0.00%)  1/1000 (0.10%) 
Breast cancer metastatic  0/997 (0.00%)  1/1000 (0.10%) 
Metastatic uterine cancer  0/743 (0.00%)  1/776 (0.13%) 
Mixed hepatocellular cholangiocarcinoma  0/997 (0.00%)  1/1000 (0.10%) 
Nervous system disorders     
Seizure  2/997 (0.20%)  0/1000 (0.00%) 
Syncope  3/997 (0.30%)  3/1000 (0.30%) 
Cerebrovascular accident  1/997 (0.10%)  0/1000 (0.00%) 
Restless legs syndrome  0/997 (0.00%)  1/1000 (0.10%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1/743 (0.13%)  0/776 (0.00%) 
Ectopic pregnancy  1/743 (0.13%)  0/776 (0.00%) 
Psychiatric disorders     
Completed suicide  1/997 (0.10%)  0/1000 (0.00%) 
Bipolar disorder  0/997 (0.00%)  1/1000 (0.10%) 
Renal and urinary disorders     
Acute kidney injury  2/997 (0.20%)  0/1000 (0.00%) 
End stage renal disease  0/997 (0.00%)  1/1000 (0.10%) 
Haematuria  0/997 (0.00%)  1/1000 (0.10%) 
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1/997 (0.10%)  0/1000 (0.00%) 
Respiratory distress  1/997 (0.10%)  0/1000 (0.00%) 
Respiratory failure  1/997 (0.10%)  0/1000 (0.00%) 
Asthma  0/997 (0.00%)  1/1000 (0.10%) 
Pulmonary embolism  0/997 (0.00%)  1/1000 (0.10%) 
Skin and subcutaneous tissue disorders     
Rash maculopapular  1/997 (0.10%)  0/1000 (0.00%) 
Vascular disorders     
Aortic stenosis  1/997 (0.10%)  0/1000 (0.00%) 
Hypertensive crisis  1/997 (0.10%)  0/1000 (0.00%) 
Aortic aneurysm  0/997 (0.00%)  1/1000 (0.10%) 
Hypertensive emergency  0/997 (0.00%)  1/1000 (0.10%) 
Hypotension  0/997 (0.00%)  1/1000 (0.10%) 
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Ferumoxytol Ferric Carboxymaltose (FCM)
Affected / at Risk (%) Affected / at Risk (%)
Total   186/997 (18.66%)   245/1000 (24.50%) 
Gastrointestinal disorders     
Nausea  35/997 (3.51%)  60/1000 (6.00%) 
Diarrhoea  29/997 (2.91%)  33/1000 (3.30%) 
Abdominal pain  17/997 (1.71%)  21/1000 (2.10%) 
Constipation  14/997 (1.40%)  13/1000 (1.30%) 
Vomiting  11/997 (1.10%)  13/1000 (1.30%) 
General disorders     
Fatigue  30/997 (3.01%)  36/1000 (3.60%) 
Chest discomfort  8/997 (0.80%)  11/1000 (1.10%) 
Pyrexia  7/997 (0.70%)  22/1000 (2.20%) 
Chest pain  10/997 (1.00%)  4/1000 (0.40%) 
Metabolism and nutrition disorders     
Hypophosphataemia  0/997 (0.00%)  18/1000 (1.80%) 
Musculoskeletal and connective tissue disorders     
Back pain  19/997 (1.91%)  16/1000 (1.60%) 
Arthralgia  14/997 (1.40%)  12/1000 (1.20%) 
Nervous system disorders     
Headache  60/997 (6.02%)  82/1000 (8.20%) 
Dizziness  25/997 (2.51%)  40/1000 (4.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  15/997 (1.50%)  13/1000 (1.30%) 
Dyspnoea  11/997 (1.10%)  18/1000 (1.80%) 
Skin and subcutaneous tissue disorders     
Pruritus  12/997 (1.20%)  11/1000 (1.10%) 
Urticaria  3/997 (0.30%)  13/1000 (1.30%) 
Vascular disorders     
Flushing  11/997 (1.10%)  16/1000 (1.60%) 
Hypertension  7/997 (0.70%)  15/1000 (1.50%) 
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If there is no multi-site publication within 18 months after the Study has been completed or terminated at all Study sites, and all data have been received by Sponsor, the Site, and 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.
Results Point of Contact
Name/Title: Medical Information
Organization: AMAG Pharmaceuticals, Inc.
Phone: 1-877-411-2510
Responsible Party: AMAG Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02694978     History of Changes
Other Study ID Numbers: AMAG-FER-IDA-304
First Submitted: February 8, 2016
First Posted: March 1, 2016
Results First Submitted: March 26, 2018
Results First Posted: June 11, 2018
Last Update Posted: June 11, 2018