A phase III, randomized, open-label, blinded endpoint, comparative trial of ferric derisomaltose versus no intravenous iron in iron-deficient subjects with symptomatic chronic heart failure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharmacosmos A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

17 Jul 2025 → ongoing

Decision date (initial)

2025-06-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pharmacosmos A/S

External identifiers

EU CT number

2024-519059-28-00

WHO UTN

U1111-1313-0493

ClinicalTrials.gov

NCT06929806

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Safety, Efficacy

To compare the efficacy of ferric derisomaltose to no IV iron on cardiovascular mortality and hospitalizations for worsening heart failure in irondeficient subjects with symptomatic CHF

Secondary objectives 4

1. Key secondary efficacy objective: To compare the efficacy of ferric derisomaltose to no IV iron on cardiovascular mortality, all-cause mortality, hospitalizations for worsening heart failure, and all-cause hospitalizations in irondeficient subjects with symptomatic CHF
2. Secondary efficacy objectives: To compare the efficacy of ferric derisomaltose to no IV iron on hospitalizations for cardiovascular, respiratory, or renal disease and other cardiovascular endpoints in iron-deficient subjects with symptomatic CHF
3. Pharmacodynamic (PD) objective: To compare the efficacy of ferric derisomaltose to no IV iron on Hb, s-ferritin, TSAT, s-iron, and total iron binding capacity (TIBC)
4. Safety objective: To assess the safety of ferric derisomaltose to no IV iron

Conditions and MedDRA coding

Chronic Heart Failure

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Subjects aged ≥18 years at the time of signing the ICF
2. 2. LVEF of ≤45 %
3. 3. History of heart failure and NYHA class II, III or IV
4. 4. Hb ≥9 g/dL and ≤13 g/dL for women; ≥9 g/dL and ≤14 g/dL for men
5. 5. TSAT <20 %
6. 6. On maximally tolerated guideline-directed medical therapy for heart failure as determined by Investigator
7. 7. Evidence of being in a higher risk heart failure group: • Currently hospitalized for worsening heart failure (hemodynamically stabilized and expected to survive to discharge). Hospital admission with, or complicated by signs of, worsening heart failure that has resulted in the use of IV diuretics or initiation of or a substantial increase in medication used to treat heart failure (e.g., increase in oral diuretics by 40 mg or more for furosemide or 1 mg or more for bumetanide and/or the addition of a thiazide like diuretic or the addition of a mineralocorticoid receptor antagonist and/or the addition of a sodium-glucose co-transporter 2 inhibitor and/or the addition of sacubitril/valsartan) • Hemodynamically stable CHF subjects identified in outpatient ambulatory services/practice or emergency departments with elevated natriuretic peptides: NT-proBNP >500 pg/mL in sinus rhythm or >1,000 pg/mL in atrial fibrillation (or BNP of >150 pg/mL or 300 pg/mL, respectively)
8. 8. At least 1 of the following prognostic enrichment criteria: • Medical history of ischemic heart failure etiology, and/or prior AMI, and/or prior coronary revascularization o eGFR ≤45 mL/min/1.73 m² o TSAT ≤15 % • Anemia as defined by a Hb of ≥9 and <12 g/dL for women and ≥9 and <13 g/dL for men
9. 9. Willingness to participate and signing the ICF

Exclusion criteria 14

1. 1. eGFR <15mL/min/1.73m² or on renal replacement therapy
2. 2. Chronic defined need for IV iron therapy
3. 3. Likely to need or already receiving ESA
4. 4. Any of the following cardiovascular comorbidities: • Planned cardiac surgery or revascularization or cardiac device implantation • Within 3 months of screening any of the following: a primary diagnosis of type 1 myocardial infarction (excluding small troponin elevations in the context of heart failure admissions), cerebrovascular accident, major cardiovascular surgery or percutaneous coronary intervention, or blood/plasma transfusion • On active cardiac transplant list • Left ventricular assist device implanted
5. 5. Any of the following other comorbidities: • Other disease with life expectancy of <2 years • Active clinically relevant bleeding in the Investigator’s opinion • Known or suspected gastrointestinal malignancy
6. 6. Pregnant or nursing women. To avoid pregnancy, women of childbearing potential must agree to use contraception as described in Section 16 during the whole trial period and at least 7 days after the last dosing if the subject decides to withdraw
7. 7. Previous serious hypersensitivity reactions to any IV iron compounds including ferric derisomaltose
8. 8. Iron overload or disturbances in utilization of iron (e.g., haemochromatosis, hemosiderosis)
9. 9. ALAT and/or ASAT >3 times upper limit of normal
10. 10. Received an investigational drug and/or invasive device within 30 days or 5 half-lives, whichever is longer, prior to screening
11. 11. Treatment with IV or IM iron within 6 months prior to screening
12. 12. Treatment with radiotherapy, chemotherapy or other drugs that suppress the bone marrow, and drugs which have anemia as side effect within 90 days prior to screening
13. 13. Any non-viral infection (non-viral infection that has been fully treated before the baseline visit is accepted)
14. 14. Any other laboratory abnormality (known B12 or folate deficiency should be corrected but do not exclude the subject), medical condition, or psychiatric disorders which, in the opinion of the Investigator, will put the subject’s disease management at risk or may result in the subject being unable to comply with the trial requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy endpoint: Number of cardiovascular deaths and hospitalizations for worsening heart failure

Secondary endpoints 20

1. Key Secondary efficacy endpoints: • Time to first hospitalization for worsening heart failure or cardiovascular death
2. Key Secondary efficacy endpoints: • Number of hospitalizations for worsening heart failure
3. Key Secondary efficacy endpoints: • Number of all-cause hospitalizations
4. Key Secondary efficacy endpoints: • Time to cardiovascular death
5. Key Secondary efficacy endpoints: • Time to all-cause death
6. Secondary efficacy endpoints: • Number of hospitalizations for cardiovascular, respiratory, or renal disease
7. Secondary efficacy endpoints: • Time to cardiovascular, respiratory, or renal death
8. Secondary efficacy endpoints: • Number of hospitalizations for cardiovascular events: stroke, acute myocardial infarct (AMI), and heart failure
9. Secondary efficacy endpoints: • Time to cardiovascular death or first hospitalization for cardiovascular event: stroke, AMI, and heart failure
10. Secondary efficacy endpoints: • Time to all-cause death or first hospitalization
11. Secondary efficacy endpoints: • Days hospitalized or dead for cardiovascular reasons at week 52
12. Secondary efficacy endpoints: • Days hospitalized or dead for any reason at week 52
13. Secondary efficacy endpoints: • Change in New York Heart Association (NYHA) from baseline to weeks 12, 26, and 52
14. Secondary efficacy endpoints: • All-cause rehospitalizations at 30 and 60 days
15. Secondary efficacy endpoints: • Rehospitalizations for worsening heart failure at 30 and 60 days
16. Secondary efficacy endpoints: • Number of cardiovascular deaths and hospitalizations for worsening heart failure including urgent and unscheduled outpatient IV diuretic treatment
17. Secondary efficacy endpoints: • Number of urgent and unscheduled outpatient IV diuretic treatment
18. PD endpoint: Change in Hb, s-ferritin, TSAT, s-iron, and TIBC from baseline to weeks 26 and 52
19. Safety endpoints: • Type and incidence of serious adverse events (SAEs)
20. Safety endpoints: • In addition, vital signs and safety laboratory parameters will be measured as part of standard safety assessments.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharmacosmos A/S

Sponsor organisation

Pharmacosmos A/S

Address

Roervangsvej 30

City

Holbaek

Postcode

4300

Country

Denmark

Scientific contact point

Organisation

Pharmacosmos A/S

Contact name

Trine Kolding

Public contact point

Organisation

Pharmacosmos A/S

Contact name

Trine Kolding

Third parties 4

Locations

12 EU/EEA countries · 141 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 174 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications