Clinical trial NCT02680756: Safety and Efficacy Study of Oral Ferric Maltol Compared to Intravenous Iron To Treat Iron Deficiency Anaemia in IBD
Official title: A Phase 3b, Randomized, Controlled, Multicentre Study With Oral Ferric Maltol (Feraccru) or Intravenous Iron (Ferric Carboxy Maltose; FCM), for the Treatment of Iron Deficiency Anaemia in Subjects With Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia, Iron-Deficiency
Inflammatory Bowel Disease
Crohn's Disease
Keywords: Iron Deficiency
Anaemia
Crohn's Disease
Deficiency Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Lead sponsor: Shield Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-02-11
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy of ferric maltol and intravenous iron (IVI) Ferric Carboxy Maltose in the treatment of iron deficiency anaemia (IDA) and subsequent maintenance of haemoglobin in subjects with Inflammatory Bowel Disease (IBD).

Detailed description: A phase 3b, randomized, controlled, multicentre study with oral ferric maltol or intravenous iron (FCM), for the treatment of iron deficiency anaemia in subjects with inflammatory bowel disease.

Approximately 242 eligible subjects will be randomised (1:1) to receive one of the following treatments for the duration of the study treatment period (52 weeks):

* Oral ferric maltol, 30 mg capsule bid.
* Intravenous iron (ferric carboxy maltose) as per SPC

In the FCM arm IV iron treatment will be repeated if the subject is iron deficient at any of the study visits.

Subject participation in the study will consist of 3 periods:

* Screening: Up to 14 days
* Randomised Treatment: 52 weeks
* Post-treatment safety follow-up: 14 days after study medication discontinuation

Primary efficacy and safety of ferric maltol and Intravenous iron (ferric carboxy maltose) will be evaluated after the first 12 weeks.

End of study evaluations will occur at Week 52 or premature discontinuation.

Eligibility criteria: All of the following criteria must be met to randomize a subject in the study:

1. Subjects must be competent to understand the information given in the Independent Ethics Committee (IEC) or Institutional Review Board (IRB) approved informed consent form and must sign and date the informed consent prior to any study mandated procedure
2. Subjects must be willing and able to comply with study requirements
3. Age ≥ 18 years
4. Subjects must have a confirmed diagnosis of IBD (endoscopic and/or biopsy)
5. Subjects must be considered suitable for intravenous iron treatment by the Investigator
6. Subjects must have iron deficiency anaemia defined by the following criteria:

   1. Hb 8.0 g/dL and ≤11.0 g/dL for women OR a Hb 8.0 g/dL and ≤12.0 g/dL for men
   2. AND Ferritin \<30ng/ml OR Ferritin \<100 ng/ml WITH Transferrin saturation (TSAT) \<20%
7. Female subjects of childbearing potential (including perimenopausal females who have had a menstrual period within 1 year prior to screening) must agree to use a reliable method of contraception until they have completed the study and for at least 4 weeks following their final study visit. Reliable contraception is defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly, such as implants, injectables, some intrauterine contraceptive devices (IUDs), complete sexual abstinence, or a vasectomized partner. Oral contraceptive medications are allowed in this study. Female subjects who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal (defined as no menstrual period within 1 year of screening) are also allowed to participate.

A subject who meets any of the following criteria is not eligible for participation in the study.

1. Subject with anaemia due to any cause other than iron deficiency, including, but not limited to:

   1. Untreated or untreatable severe malabsorption syndrome
   2. Immunosuppressant use. Immunosuppressants are permitted so long as there is no clinical evidence or suspicion of the immunosuppressant contributing to the subject's anaemia or affecting erythropoiesis.

   Variations to dosing are permitted at the discretion of the investigator so long as there is no clinical evidence or suspicion of the immunosuppressant contributing to the subject's anaemia or affecting erythropoiesis
2. Subject who has received prior to screening:

   1. Within 8 weeks intramuscular or intravenous (IV) iron or administration of depot iron preparation
   2. Within 2 weeks a blood transfusion
   3. Oral iron supplementation, taken specifically to treat anaemia, within the previous 4 weeks (Over the Counter (OTC) multivitamins containing iron are permitted)
3. Subjects with active inflammatory bowel disease as defined by a SCCAI score greater than 5 at Screening or a CDAI score greater than 300 in the Screening period (as assessed using the Screening haematocrit (HCT) and CDAI diary card completed by the subject for 7 days prior to planned randomization).
4. Subjects with known hypersensitivity or allergy to either the active substance or excipients of ferric maltol capsules or ferric carboxymaltose solution for IV administration
5. Subjects who have had serious adverse reactions to previous doses of ferric carboxymaltose or any other intravenous iron.
6. Subjects with contraindication for treatment with iron preparations, e.g. hemochromatosis, chronic hemolytic disease, sideroblastic anaemia, thalassemia, or lead intoxication induced anaemia.
7. Subjects with vitamin B12 or folic acid deficiency as determined by the central laboratory screening results. Subjects may start vitamin B12 or folate replacement and rescreen after at least 2 weeks.
8. Subjects who are pregnant or breast feeding.
9. Concomitant medical conditions with significant active bleeding likely to initiate or prolong anaemia.
10. Participation in any other interventional clinical study within 30 days prior to screening.
11. Subject with cardiovascular, liver, renal, haematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject or severely limit the lifespan of the subject (i.e. unlikely to complete the full duration of the study).
12. Subject with significant neurologic or psychiatric symptoms resulting in disorientation, memory impairment, or inability to report accurately that might interfere with treatment compliance, study conduct or interpretation of the results (e.g., Alzheimer's disease, schizophrenia or other psychosis, active or current alcohol or drug abuse)
13. Subject who is an inmate of a psychiatric ward, prison, or other state institution.
14. Subject who is an Investigator or any other team member involved directly or indirectly in the conduct of the clinical study.
15. Subjects with severe renal impairment: creatinine clearance \<30 mL/min. (Applicable to US sites Only)

Primary outcomes:
measure: Number of Subjects Achieving Either a 2g/dL Increase in Hb OR Normalization of Hb at Week 12
timeFrame: Baseline to Week 12
measure: Number of Subjects Achieving Either a 2g/dL Increase in Hb OR Normalization of Hb at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in Hb Concentration From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in Hb Concentration From Baseline to Week 12 in Subjects With a Baseline Hb <9.5 g/dL
timeFrame: Baseline to Week 12
measure: Number of Subjects Who Experience a Change From Baseline in Hb Concentration ≥1.0 g/dL at Week 12
timeFrame: Baseline to Week 12
measure: Number of Subjects With Baseline Hb <9.5g/dL That Achieve an Increase in Hb Concentration of ≥1 g/dL at Week 12
timeFrame: Baseline to Week 12
measure: Number of Subjects With Hb Concentration Within Normal Limits at Week 12
timeFrame: Baseline to Week 12
measure: Number of Subjects With Baseline Hb Concentration <9.5 g/dL That is Within Normal Limits at Week 12
timeFrame: Baseline to Week 12
measure: Proportion of Subjects Who Are Non-anaemic at 6 Months and 12 Months
timeFrame: Baseline to Month 6
measure: Change in Hb Concentration From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: Change in Hb Concentration From Baseline to Week 4 in Subjects With a Baseline Hb <9.5 g/dL
timeFrame: Baseline to Week 4
measure: Number of Subjects Who Experience a Change From Baseline in Hb Concentration ≥2.0 g/dL at Week 12
timeFrame: Baseline to Week 12
measure: Number of Subjects With Baseline Hb <9.5g/dL That Achieve an Increase in Hb Concentration of ≥2 g/dL at Week 12
timeFrame: Baseline to Week 12
measure: Number of Subjects Who Experience a Change From Baseline in Hb Concentration ≥1.0 g/dL at Week 4
timeFrame: Baseline to Week 4
measure: Number of Subjects With Baseline Hb <9.5g/dL That Achieve an Increase in Hb Concentration of ≥1 g/dL at Week 4
timeFrame: Baseline to Week 4
measure: Number of Subjects With Hb Concentration Within Normal Limits at Week 4
timeFrame: Baseline to Week 4
measure: Number of Subjects With Baseline Hb Concentration <9.5 g/dL That is Within Normal Limits at Week 4
timeFrame: Baseline to Week 4
measure: Number of Subjects Who Experience a Change From Baseline in Hb Concentration ≥2.0 g/dL at Week 4
timeFrame: Baseline to Week 4
measure: Number of Subjects With Baseline Hb <9.5g/dL That Achieve an Increase in Hb Concentration of ≥2 g/dL at Week 4
timeFrame: Baseline to Week 4
Other outcomes:
measure: Change From Baseline Physical Component and Mental Component Score
timeFrame: Baseline to Week 52 (LOCF)
measure: Number of Patients With Treatment-emergent Adverse Events (AEs)
timeFrame: Baseline to Week 52
measure: Number of Patients With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Baseline to Week 52
Locations:
city: Dothan
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Gainesville
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Chevy Chase
country: United States
state: Maryland
city: Saint Paul
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Great Neck
country: United States
state: New York
city: Lima
country: United States
state: Ohio
city: Germantown
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Beaumont
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Bellevue
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Gent
country: Belgium
city: Clichy
country: France
city: Lille
country: France
city: Lyon
country: France
city: Saint Etienne
country: France
city: Salouel
country: France
city: Vandœuvre-lès-Nancy
country: France
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Jena
country: Germany
city: Leipzig
country: Germany
city: Lubeck
country: Germany
city: Luneburg
country: Germany
city: Minden
country: Germany
city: Oldenburg
country: Germany
city: Schweinfurt
country: Germany
city: Budapest
country: Hungary
city: Miskolc
country: Hungary
city: Szeged
country: Hungary
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Girona
country: Spain
city: Madrid
country: Spain
city: Santiago de Compostela
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Shield Therapeutics
name: Jackie Mitchell, PhD
role: STUDY_DIRECTOR
References: