Treatment Response of Injectafer vs Oral Iron to Baseline Hepcidin Levels in Patients With Iron Deficiency Anemia (IDA) Secondary to Inflammatory Bowel Disease (IBD) or Gastric Bypass

• ClinicalTrials.gov Identifier: NCT02086968
• Recruitment Status: Completed
• First Posted: March 13, 2014
• Results First Posted: September 17, 2020
• Last Update Posted: September 17, 2020
• Sponsor: American Regent, Inc.
• Information provided by (Responsible Party): American Regent, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Iron Deficiency Anemia Secondary to IBD or Gastric Bypass
• Interventions: Drug: Injectafer; Drug: Ferrous Sulfate tablets
• Enrollment: 198

Participant Flow

Recruitment Details	This study was conducted at 41 study centers in the United States. The first subject was screened on 06 February 2014 and the last subject was completed on 07 July 2016.
Pre-assignment Details

Arm/Group Title	Injectafer	Ferrous Sulfate Tablets
Arm/Group Description	2 doses of Injectafer, at 15 mg/kg for a maximum single dose of 750 mg given on Days 0 and 7 for a total of up to 1500 mg	Oral Ferrous Sulfate at 325 mg (1 tablet) three times a day for 28 days
Period Title: Overall Study
Started	100	98
Completed	92	85
Not Completed	8	13
Reason Not Completed
Adverse Event	1	5
Lost to Follow-up	2	3
Study drug received outside protocol	0	1
Physician Decision	4	0
Withdrawal by Subject	1	4

Baseline Characteristics

Arm/Group Title		Injectafer	Ferrous Sulfate Tablets	Total
Arm/Group Description		2 doses of Injectafer, at 15 mg/kg for a maximum single dose of 750 mg given on Days 0 and 7 for a total of up to 1500 mg Injectafer: 2 doses of Injectafer, at 15mg/kg for a maximum single dose of 750mg given on days 0 and 7 for a total of up to 1500mg	Oral Ferrous Sulfate at 325 mg (1 tablet) three times a day for 28 days Ferrous Sulfate tablets: 325mg (1 tablet) three times a day for 28 days	Total of all reporting groups
Overall Number of Baseline Participants		99	97	196
Baseline Analysis Population Description		Of the 198 subjects randomized, two subjects (one in each group) were not treated.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	99 participants	97 participants	196 participants
		38.3; (18.6 to 85.5)	43.0; (18.5 to 74.3)	40.5; (18.5 to 85.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	99 participants	97 participants	196 participants
	Female	76 76.8%	66 68.0%	142 72.4%
	Male	23 23.2%	31 32.0%	54 27.6%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants
White	Number Analyzed	97 participants	97 participants	194 participants
		72	79	151
Black/African American	Number Analyzed	97 participants	97 participants	194 participants
		25	17	42
Asian	Number Analyzed	97 participants	97 participants	194 participants
		1	1	2
American Indian/Alaska Native	Number Analyzed	97 participants	97 participants	194 participants
		0	1	1
		[1] Measure Analysis Population Description: The category of Race is Check All That Apply. In the Injectafer group, two subjects didn't check any options and one subject checked two options. In the Oral Iron group, one subject checked two options.
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	99 participants	97 participants	196 participants
		99 100.0%	97 100.0%	196 100.0%
Point of Care Hemoglobin [1]; Mean (Standard Deviation); Unit of measure: g/dL
	Number Analyzed	99 participants	95 participants	194 participants
		9.3 (1.19)	9.4 (0.99)	9.3 (1.10)
		[1] Measure Analysis Population Description: Included subjects who received at least 1 dose of randomized treatment and had at least 1 post-randomization measurement of hemoglobin

Outcome Measures

1. Primary Outcome

Title	Correlation Between Screening Hepcidin and Change in Hemoglobin From Baseline to Highest Observed Hemoglobin Change (Proportion of Responders).
Description	Responders were defined as subjects achieving an increase from baseline ≥2 g/dL at anytime between baseline and the end of the study (Day 28). The relation between screening hepcidin and change in hemoglobin was assessed with regression models with baseline hepcidin and treatment group as independent factors. Treatment group differences (oral vs. IV iron) for mean changes in endpoints were assessed with the analysis of covariance with a fixed factor for treatment and baseline value as covariate. Treatment group differences for proportions were assessed with the normal approximation to the binomial distribution.
Time Frame	anytime between baseline and end of study (day 28) or time of intervention

Outcome Measure Data

Analysis Population Description

Full analysis set population

Arm/Group Title	Injectafer	Ferrous Sulfate Tablets
Arm/Group Description:	2 doses of Injectafer, at 15 mg/kg for a maximum single dose of 750 mg given on Days 0 and 7 for a total of up to 1500 mg Injectafer: 2 doses of Injectafer, at 15mg/kg for a maximum single dose of 750mg given on days 0 and 7 for a total of up to 1500mg	Oral Ferrous Sulfate at 325 mg (1 tablet) three times a day for 28 days Ferrous Sulfate tablets: 325mg (1 tablet) three times a day for 28 days
Overall Number of Participants Analyzed	94	92
Measure Type: Count of Participants; Unit of Measure: Participants
	60 63.8%	34 37.0%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Injectafer		Ferrous Sulfate Tablets
Arm/Group Description	2 doses of Injectafer, at 15 mg/kg for a maximum single dose of 750 mg given on Days 0 and 7 for a total of up to 1500 mg Injectafer: 2 doses of Injectafer, at 15mg/kg for a maximum single dose of 750mg given on days 0 and 7 for a total of up to 1500mg		Oral Ferrous Sulfate at 325 mg (1 tablet) three times a day for 28 days Ferrous Sulfate tablets: 325mg (1 tablet) three times a day for 28 days
All-Cause Mortality
	Injectafer		Ferrous Sulfate Tablets
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/99 (0.00%)		0/97 (0.00%)
Serious Adverse Events
	Injectafer		Ferrous Sulfate Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/99 (3.03%)		1/97 (1.03%)
Gastrointestinal disorders
Colitis ulcerative † 1	1/99 (1.01%)	1	0/97 (0.00%)	0
Crohn's disease † 1	0/99 (0.00%)	0	1/97 (1.03%)	1
Large intestinal obstruction † 1	1/99 (1.01%)	1	0/97 (0.00%)	0
Small intestinal obstruction † 1	0/99 (0.00%)	0	1/97 (1.03%)	1
Infections and infestations
Clostridium difficile colitis † 1	1/99 (1.01%)	1	0/97 (0.00%)	0
1 Term from vocabulary, MedDRA (16.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Injectafer		Ferrous Sulfate Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/99 (33.33%)		24/97 (24.74%)
Gastrointestinal disorders
Abdominal pain * 1	1/99 (1.01%)	1	5/97 (5.15%)	5
Abdominal pain upper * 1	0/99 (0.00%)	0	3/97 (3.09%)	3
Constipation * 1	1/99 (1.01%)	1	10/97 (10.31%)	10
Diarrhoea * 1	0/99 (0.00%)	0	3/97 (3.09%)	3
Dyspepsia * 1	2/99 (2.02%)	2	0/97 (0.00%)	0
Faeces discoulered * 1	0/99 (0.00%)	0	3/97 (3.09%)	3
Flatulence * 1	0/99 (0.00%)	0	2/97 (2.06%)	2
Nausea * 1	2/99 (2.02%)	2	6/97 (6.19%)	6
Rectal haemorrhage * 1	0/99 (0.00%)	0	2/97 (2.06%)	2
Vomiting * 1	0/99 (0.00%)	0	5/97 (5.15%)	5
Immune system disorders
Hypersensitivity * 1	2/99 (2.02%)	2	0/97 (0.00%)	0
Investigations
Blood phosphorous decreased * 1	10/99 (10.10%)	10	0/97 (0.00%)	0
Metabolism and nutrition disorders
Hypophosphataemia * 1	5/99 (5.05%)	5	0/97 (0.00%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain * 1	2/99 (2.02%)	2	0/97 (0.00%)	0
Nervous system disorders
Headache * 1	4/99 (4.04%)	4	0/97 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus * 1	3/99 (3.03%)	3	0/97 (0.00%)	0
Urticaria * 1	2/99 (2.02%)	2	0/97 (0.00%)	0
1 Term from vocabulary, MedDRA (16.1); * Indicates events were collected by non-systematic assessment

Limitations and Caveats

The study was stopped early due to slow enrollment, however it was not considered prematurely terminated. A total of 198 of the 400 subjects planned were randomized, 196 were treated, and the study concluded normally.

More Information

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.

Sponsor reserves the right to publish the results collected from all sites. PI may publish results from a specific site if there is no multi-site publication within 12 months of the conclusion, abandonment or termination of the study. PI must provide sponsor with copy of draft publication at least 60 days before the scheduled submission to allow sponsor to protect confidential information. PI must withhold submission of publication for 90 days to allow sponsor to seek patent protection.

Results Point of Contact

• Name/Title: Angelia Butcher
• Organization: Luitpold Pharmaceuticals, Inc.
• Phone: 610-650-4200 ext 811
• EMail: abutcher@lpicrd.com

• Responsible Party: American Regent, Inc.
• ClinicalTrials.gov Identifier: NCT02086968
• Other Study ID Numbers: 1VIT13035
• First Submitted: March 12, 2014
• First Posted: March 13, 2014
• Results First Submitted: December 11, 2017
• Results First Posted: September 17, 2020
• Last Update Posted: September 17, 2020