Blinded Randomized Placebo-Controlled Study Efficacy and Safety of Injectafer in ID Patients With Fibromyalgia

• Sponsor: American Regent, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02409459
• Collaborator: (none)
• Enrollment: 81
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

This study investigates the efficacy and safety of an IV iron Injectafer in the treatment of iron deficient patients with fibromyalgia. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 42 days.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency; Fibromyalgia	Drug: Injectafer; Drug: Placebo	Phase 2

Detailed Description

This is a blinded, randomized, placebo-controlled study. All subjects who meet the inclusion requirements and no exclusion criteria will be entered into an up to 14 day screening phase. Eligible subjects will be randomized in a 1:1 ratio to receive Injectafer or Placebo on days 0 and 5. All treated subjects will be followed for efficacy and safety for 42 days. Subjects will visit the clinic on days 0 and 5 for treatment, and then on days 14, 28, and 42. The subject's participation in the study will be for approximately 42 days from day 0.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Blinded, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Injectafer (Ferric Carboxymaltose) in the Treatment of Iron Deficient Patients With Fibromyalgia
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Injectafer 15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute	Drug: Injectafer; Other Names: Ferric Carboxymaltose (FCM)
Placebo Comparator: Placebo 15 cc of Normal Saline IV push at 2 ml/minute	Drug: Placebo; Normal saline solution; Other Names: Saline solution

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With a ≥13 Point Improvement in FIQR Score [Day 42]

   The primary efficacy endpoint was the percentage of subjects who had a ≥13-point improvement in the FIQR from baseline to Day 42.

Secondary Outcome Measures

1. Change in BPI, Pain Interference [Change from Baseline in Brief Pain Inventory Pain Interference Score at Day 42]

   The short version of the Brief Pain Inventory (BPI) includes front and back body diagrams, 4 pain severity items and 7 pain interference items rated on 0-10 scales (with 0 being the best outcome and 10 being the worst outcome), and a question about percentage of pain relief by analgesics. The Pain Interference Score is calculated by adding the scores for the 7 pain interference questions and then dividing by 7 to give a score out of 10.

2. Change in FIQR Score [Change from Baseline in FIQR score at Day 42]

   The FIQR has 21 individual questions. All questions are based on an 11-point numeric rating scale of 0 to 10, with 10 being 'worst' and all questions are framed in the context of the past 7 days. The summed score for function (range 0 to 90) is divided by 3, the summed score for overall impact (range 0 to 20) is not changed, and the summed score for symptoms (range 0 to 100) is divided by 2. The total FIQR is the sum of the three modified domain scores.

3. Change in BPI, Pain Severity [Change from Baseline in Brief Pain Inventory Pain Severity Score at Day 42]

   The short version of the Brief Pain Inventory (BPI) includes front and back body diagrams, 4 pain severity items and 7 pain interference items rated on 0-10 scales (with 0 being the best outcome and 10 being the worst outcome), and a question about percentage of pain relief by analgesics. The Pain Severity Score is calculated by adding the scores for the 4 pain severity questions and then dividing by 4 to give a severity score out of 10.

4. Change in Fatigue Visual Numeric Scale [Change from Baseline in Fatigue Visual Numeric Scale at Day 42]

   Scores range from 0 to 10, with the higher score indicating more fatigue.

5. Change in Iron Indices, Serum Ferritin [Change from Baseline in Iron Indices, Serum ferritin at Day 42]

6. Change in Iron Indices - Transferrin Saturation [Change from baseline in Iron Indices, Transferrin saturation, at Day 42]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subject's ≥ 18 years of age, able to give informed consent to the study.

• Fibromyalgia diagnosis based on The 2011 modification of the American College of Rheumatology (ACR) 's 2010 preliminary criteria for diagnosing fibromyalgia (2011ModCr)

• A baseline score ≥ 60 on the FIQR

• Subject's current medications to treat fibromyalgia, including pain medicines, anti-depressants, sleep medications must be on a stable dose for at least 30 days.

• Subject's current narcotic medication must be on a stable dose for at least 30 days prior to randomization

• Subjects at risk for pregnancy must have a negative pregnancy test at baseline and be practicing an acceptable form of birth control: have had a hysterectomy or tubal ligation, or otherwise be incapable of pregnancy, or have practiced any of the following methods of contraception for at least one month prior to study entry: hormonal contraceptives, spermicide and barrier, intrauterine device, partner sterility.

Exclusion Criteria:

• Parenteral iron use within 4 weeks prior to screening.

• History of > 10 blood transfusions in the past 2 years.

• Anticipated need for blood transfusion during the study.

• Known hypersensitivity reaction to any component of Injectafer® (Ferric Carboxymaltose).

• Current or acute or chronic infection other than viral upper respiratory tract infection

• Malignancy (other than basal or squamous cell skin cancer or the subject has been cancer free for ≥ 5 years).

• Active inflammatory arthritis (e.g. rheumatoid arthritis, SLE).

• Pregnant or lactating women.

• Severe peripheral vascular disease with significant skin changes.

• Seizure disorder currently being treated with medication.

• Baseline ferritin ≥ 50 ng/mL.

• Baseline TSAT ≥ 20%.

• History of hemochromatosis or hemosiderosis or other iron storage disorders.

• Known positive hepatitis with evidence of active disease.

• Hemoglobin greater than the upper limit of normal.

• Calcium or phosphorous outside the normal range.

• Known positive hepatitis B antigen (HBsAg) or hepatitis C viral antibody (HCV) with evidence of active hepatitis (i.e., AST/ALT greater than the upper limit of normal).

• Known positive HIV-1/HIV-2 antibodies (anti-HIV)

• Received an investigational drug within 30 days before randomization.

• Chronic alcohol or drug abuse within the past 6 months.

• Any other pre-existing laboratory abnormality, medical condition or disease which in view of the investigator participation in this study may put the subject at risk.

• Subject unable to comply with the study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Solutions	Franklin	Tennessee	United States	37064

Sponsors and Collaborators

• American Regent, Inc.

Investigators

• Study Director: Mark A Falone, MD, American Regent, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: American Regent, Inc.
• ClinicalTrials.gov Identifier: NCT02409459
• Other Study ID Numbers: 1VIT14038
• First Posted: Apr 6, 2015
• Last Update Posted: Feb 20, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Fibromyalgia; Myofascial Pain Syndromes

Study Results

Participant Flow

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Period Title: Overall Study
STARTED	41	40
COMPLETED	40	39
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo	Injectafer	Total
Arm/Group Description	Group B: Placebo	Group A: Injectafer	Total of all reporting groups
Overall Participants	40	41	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44 (10.85)	41 (11.07)	43 (10.97)
Sex: Female, Male (Count of Participants)
Female	40 100%	40 97.6%	80 98.8%
Male	0 0%	1 2.4%	1 1.2%
Race/Ethnicity, Customized (Count of Participants)
African American	7 17.5%	7 17.1%	14 17.3%
Asian	0 0%	1 2.4%	1 1.2%
Caucasian	30 75%	33 80.5%	63 77.8%
Hispanic	2 5%	0 0%	2 2.5%
Other	1 2.5%	0 0%	1 1.2%
History of iron intolerance (Count of Participants)
No	37 92.5%	35 85.4%	72 88.9%
Yes	3 7.5%	6 14.6%	9 11.1%
History of drug allergy (Count of Participants)
No	17 42.5%	21 51.2%	38 46.9%
Yes	23 57.5%	20 48.8%	43 53.1%
IRLS score per Arm/Group (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16.3 (14.9)	13.4 (13.16)	14.8 (14.04)

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With a ≥13 Point Improvement in FIQR Score
Description	The primary efficacy endpoint was the percentage of subjects who had a ≥13-point improvement in the FIQR from baseline to Day 42.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

The Safety population consisted of all subjects who received at least one dose of randomized treatment. The Efficacy Evaluable Population consisted of all subjects who received at least 1 dose of randomized treatment with at least 1 completed post treatment FIQR evaluation.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	39	39
Count of Participants [Participants]	30 75%	26 63.4%

2. Secondary Outcome

Title	Change in BPI, Pain Interference
Description	The short version of the Brief Pain Inventory (BPI) includes front and back body diagrams, 4 pain severity items and 7 pain interference items rated on 0-10 scales (with 0 being the best outcome and 10 being the worst outcome), and a question about percentage of pain relief by analgesics. The Pain Interference Score is calculated by adding the scores for the 7 pain interference questions and then dividing by 7 to give a score out of 10.
Time Frame	Change from Baseline in Brief Pain Inventory Pain Interference Score at Day 42

Outcome Measure Data

Analysis Population Description

Patients without a particular measure at a required time point were excluded from the analysis of that measure.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	38	39
Mean (Standard Deviation) [units on a scale]	-4.1 (3.3)	-2.3 (2.6)

3. Secondary Outcome

Title	Change in FIQR Score
Description	The FIQR has 21 individual questions. All questions are based on an 11-point numeric rating scale of 0 to 10, with 10 being 'worst' and all questions are framed in the context of the past 7 days. The summed score for function (range 0 to 90) is divided by 3, the summed score for overall impact (range 0 to 20) is not changed, and the summed score for symptoms (range 0 to 100) is divided by 2. The total FIQR is the sum of the three modified domain scores.
Time Frame	Change from Baseline in FIQR score at Day 42

Outcome Measure Data

Analysis Population Description

Patients without a particular measure at a required time point were excluded from the analysis of that measure.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	38	39
Mean (Standard Deviation) [units on a scale]	-45.0 (29.5)	-29.7 (27.0)

4. Secondary Outcome

Title	Change in BPI, Pain Severity
Description	The short version of the Brief Pain Inventory (BPI) includes front and back body diagrams, 4 pain severity items and 7 pain interference items rated on 0-10 scales (with 0 being the best outcome and 10 being the worst outcome), and a question about percentage of pain relief by analgesics. The Pain Severity Score is calculated by adding the scores for the 4 pain severity questions and then dividing by 4 to give a severity score out of 10.
Time Frame	Change from Baseline in Brief Pain Inventory Pain Severity Score at Day 42

Outcome Measure Data

Analysis Population Description

Patients without a particular measure at a required time point were excluded from the analysis of that measure.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	38	39
Mean (Standard Deviation) [units on a scale]	-3.1 (2.7)	-1.8 (2.1)

5. Secondary Outcome

Title	Change in Fatigue Visual Numeric Scale
Description	Scores range from 0 to 10, with the higher score indicating more fatigue.
Time Frame	Change from Baseline in Fatigue Visual Numeric Scale at Day 42

Outcome Measure Data

Analysis Population Description

Patients without a particular measure at a required time point were excluded from the analysis of that measure.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	37	39
Mean (Standard Deviation) [units on a scale]	-3.7 (3.2)	-1.7 (2.2)

6. Secondary Outcome

Title	Change in Iron Indices, Serum Ferritin
Time Frame	Change from Baseline in Iron Indices, Serum ferritin at Day 42

Outcome Measure Data

Analysis Population Description

Patients without a particular measure at a required time point were excluded from the analysis of that measure.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	39	38
Mean (Standard Deviation) [ug/L]	292.5 (145.9)	2.0 (13.8)

7. Secondary Outcome

Title	Change in Iron Indices - Transferrin Saturation
Time Frame	Change from baseline in Iron Indices, Transferrin saturation, at Day 42

Outcome Measure Data

Analysis Population Description

Patients without a particular measure at a required time point were excluded from the analysis of that measure.

Arm/Group Title	Injectafer	Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer	15 cc of Normal Saline IV push at 2 ml/minute Normal Saline
Measure Participants	39	38
Mean (Standard Deviation) [percent of transferrin saturation]	24.4 (11.4)	5.8 (15.1)

Adverse Events

Time Frame	7 months
Arm/Group Title	Injectafer		Placebo
Arm/Group Description	15 mg/kg up to 750 mg undiluted blinded dose of IV Injectafer (ferric carboxymaltose) at 100 mg/minute Injectafer		15 cc of Normal Saline IV push at 2 ml/minute Placebo: Normal saline solution
All Cause Mortality
	Injectafer		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)
Serious Adverse Events
	Injectafer		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Injectafer		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/41 (39%)		2/40 (5%)
Ear and labyrinth disorders
Ear discomfort	1/41 (2.4%)	1	0/40 (0%)	0
Gastrointestinal disorders
Nausea	3/41 (7.3%)	3	0/40 (0%)	0
Infections and infestations
Oral herpes	0/41 (0%)	0	1/40 (2.5%)	1
Metabolism and nutrition disorders
Dehydration	0/41 (0%)	0	1/40 (2.5%)	1
Nervous system disorders
Dizziness	2/41 (4.9%)	2	0/40 (0%)	0
Dysgeusia	1/41 (2.4%)	1	0/40 (0%)	0
Headache	1/41 (2.4%)	1	0/40 (0%)	0
Paraesthesia	1/41 (2.4%)	1	0/40 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis	1/41 (2.4%)	1	0/40 (0%)	0
Vascular disorders
Flushing	6/41 (14.6%)	6	0/40 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.