ORal IrON Supplementation With Ferric Maltol in Patients With Pulmonary Hypertension (ORION-PH-1) (ORION-PH-1)

A Pilot Study to Explore Preliminary Safety, Tolerability and Efficacy of ORal IrON Supplementation With Ferric Maltol in Treating Iron Deficiency in Patients With Pulmonary Hypertension and Iron Deficiency Anemia

This is an explorative, open-label, uncontrolled, single center study to explore the preliminary safety, tolerability and efficacy of oral ferric maltol in treating iron deficiency in patients with pulmonary hypertension and iron deficiency anemia.

Study Overview

• Status: Terminated
• Conditions: Hypertension, Pulmonary; Anemia, Iron Deficiency
• Intervention / Treatment: Drug: Ferric maltol 30 mg (Feraccru®)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed written informed consent prior to any study-related procedure and willingness to comply with treatment and follow-up procedures
2. Male and female patients ≥18 years at day of inclusion
3. Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial
4. Patients with a diagnosis of PH confirmed by a (historical) right heart catheterization showing a mean pulmonary artery pressure ≥25 mmHg at rest and stable PH medication for at least 3 months.
5. 6 min walk distance >50 m
6. Mild-to-moderate iron-deficiency anemia as defined by a hemoglobin concentration ≥7 g/dl and <12 g/dl in females or ≥8 g/dl and <13 g/dl in males, and serum ferritin <100 µg/l, or 100-300 µg/l and transferrin saturation <20% at screening
7. Prevention of pregnancy:

Women without childbearing potential defined as follows:

• at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or
• hysterectomy or uterine agenesis or
• ≥ 50 years and in postmenopausal state ≥ 1 year or
• < 50 years and in postmenopausal state ≥ 1 year with serum FSH > 40 IU/l and serum oestrogen < 30 ng/l or a negative oestrogen test or

Women of childbearing potential with a negative ß-HCG pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of four weeks following the last administration of study medication:

• correct use of contraception methods. The following are acceptable: hormonal contraceptives (combined oral contraceptives and oestrogen-free pills with desogestrel, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUS) or a barrier method, e.g. condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam, gel, film, cream or suppository)
• true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception)
• sexual relationship only with female partners and/or sterile male partners

Exclusion Criteria:

1. Active hematological disorders other than iron-deficiency anemia
2. Other medical condition that according to the investigator's assessment is causing or contributing to anemia
3. Active malignancy
4. Active infectious disease
5. Active bleeding
6. Severe renal insufficiency (glomerular filtration rate <30 ml/min)
7. Severe liver injury as indicated by serum aminotransferases >3 x upper limit of normal or bilirubin levels >50 µmol/l
8. Ongoing oral or intravenous iron supplementation
9. Hemoglobin <7 g/dl in females or <8 g/dl in males at screening
10. Concomitant erythropoietin medication
11. Pregnancy or lactation period
12. Subject has received any investigational medication or any investigational device within 30 days prior to the first dose of study medication or is actively participating in any investigational drug/devices trial, or is scheduled to receive an investigational drug/device during the course of the study.
13. Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product
14. Known haemochromatosis or other iron overload syndromes
15. Patients who have been receiving repeated (>1) blood transfusions during the past 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferric maltol 30 mg (Feraccru®); Treatment with Feraccru® 30 mg hard capsules (Ferric maltol 30 mg). One capsule twice daily, morning and evening, on an empty stomach for 12 weeks	Drug: Ferric maltol 30 mg (Feraccru®); Feraccru® 30 mg hard capsules will be used. Each capsule contains 30 mg iron (as ferric maltol), 91.5 mg of lactose, 0.5 mg of Allura Red AC (E129) and 0.3 mg Sunset Yellow FCF (E110) as excipients with known effects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin level from baseline to week 12	measurement of hemoglobin in blood	baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin from baseline to week 6	measurement of hemoglobin in blood	baseline to week 6
Change in serum ferritin levels from baseline to week 6 and 12	measurement of serum ferritin levels	baseline to week 6 and baseline to week 12
Change in transferrin saturation from baseline to week 6 and 12	measurement of transferrin saturation	baseline to week 6 and baseline to week 12
Change in 6 min walking distance from baseline to week 12	measurement of functional exercise capacity	baseline to week 12
Change in serum NT-proBNP from baseline to weeks 6 and 12	measurement of serum NT-proBNP	baseline to week 6 and baseline to week 12
Change in echocardiographic markers of right ventricular function from baseline to week 12 (1)	measurement of right atrial area	from baseline to week 12
Change in echocardiographic markers of right ventricular function from baseline to week 12 (2)	measurement of right ventricular diameter	from baseline to week 12
Change in echocardiographic markers of right ventricular function from baseline to week 12 (3)	measurement of fractional area change	from baseline to week 12
Change in echocardiographic markers of right ventricular function from baseline to week 12 (4)	measurement of tricuspid annular plane systolic excursion	from baseline to week 12
Change in World Health Organization Functional Class (WHO FC) from baseline to week 6 and week 12	measurement of different parameter according to an evaluated process	from baseline to week 6 and week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events [Safety and Tolerability]	Number of Adverse Events	first application of IMP until 4 weeks after treatment discontinuation
Incidence of Serious Adverse Events [Safety and Tolerability]	Number of Serious Adverse Events	first application of IMP until 4 weeks after treatment discontinuation

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: Shields, Shields and Associates
• Investigators: Principal Investigator: Marius Hoeper, Prof. Dr., Hannover Medical School, Department of Pneumology

Publications and helpful links

General Publications

• Olsson KM, Fuge J, Brod T, Kamp JC, Schmitto J, Kempf T, Bauersachs J, Hoeper MM. Oral iron supplementation with ferric maltol in patients with pulmonary hypertension. Eur Respir J. 2020 Nov 12;56(5):2000616. doi: 10.1183/13993003.00616-2020. Print 2020 Nov.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 27, 2018
• Primary Completion (ACTUAL): March 19, 2020
• Study Completion (ACTUAL): March 19, 2020

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (ACTUAL): December 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 17, 2020
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Iron Deficiency
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Hypertension; Anemia, Iron-Deficiency; Anemia; Hypertension, Pulmonary; Hematinics; Ferric maltol
• Other Study ID Numbers: ORION-PH-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No