Mangafodipir - an intracellular contrast agent for Magnetic Resonance Imaging (MRI): Measuring manganese uptake rate in heart failure patients with preserved ejection fraction (HFpEF) patients.

2023-508118-40-01 Protocol MNC001 Therapeutic exploratory (Phase II) Ended

Start 22 Nov 2024 · End 29 Nov 2025 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol MNC001

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 42
Countries 1
Sites 1

Heart Failure

To quantify the manganese uptake rate after administration of mangafodipir trisodium in all segments of the left ventricular wall.

Key facts

Sponsor
IC Targets AS
Participant type
Healthy volunteers, Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
22 Nov 2024 → 29 Nov 2025
Decision date (initial)
2024-09-20
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
IC Targets AS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To quantify the manganese uptake rate after administration of mangafodipir trisodium in all segments of the left ventricular wall.

Secondary objectives 2

  1. Efficacy: Comparison of manganese uptake rate constant in healthy volunteers, HFpEF with HCM or CA.
  2. Safety: To assess the safety of mangafodipir trisodium injection.

Conditions and MedDRA coding

Heart Failure

VersionLevelCodeTermSystem organ class
20.0 LLT 10019279 Heart failure 10007541

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Run-in Phase
A run-in phase will include up to 6 participants (healthy volunteers and patients with HFpEF regardless of aetiology). These 6 participants will be enrolled to standardise the trial procedures, especially mangafodipir-enhanced imaging. This phase ensures that the imaging protocols, implementation, timing, and the storage and analysis of imaging data are optimised.
 Not Applicable None
2 Main Phase
The main phase will include all 36 participants. All will receive a single dose of both auxiliary and test products.
 Not Applicable None Patients with HFpEF due to HCM: 12 patients with heart failure with preserved ejection fraction due to hypertrophic cardiomyopathy
Patients with HFpEF due to CA: 12 patients with heart failure with preserved ejection fraction due to cardiac amyloidosis
HV: 12 Healthy volunteers

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2023-508118-40-00 A Phase 2 Proof-of-Concept clinical trial to quantify myocardial manganese uptake rate by cardiovascular magnetic resonance imaging following mangafodipir trisodium administration in healthy volunteers and heart failure patients with preserved ejection fraction caused by hypertrophic cardiomyopathy or cardiac amyloidosis. IC Targets AS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Participants who have given their signed declaration of consent and data protection declaration.
  2. Males and females (postmenopausal or surgically sterile females) aged ≥ 18 years and ≤ 90 years
  3. HFpEF (= LVEF > 50%) with NYHA (New York Heart Association) class I, II and III and objective evidence of cardial structural and/or functional abnormalitieconsistent with the presence of LV diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides.
  4. Patients with HCM or CA (according to current guidelines).
  5. Kidney functions eGFR (Estimated Glomerular Filtration Rate) > 30 mL/min/1.73 m2
  6. Healthy volunteers (cohort specific criteria): adults with no known pre-existing medical condition.

Exclusion criteria 23

  1. Tachycardia (heart rate >100, R-R interval <600ms)
  2. NYHA IV
  3. Previous coronary artery disease requiring intervention, including history of myocardial infarction including septal reduction therapies.
  4. Severely reduced renal function, defined as eGFR (Estimated Glomerular Filtration Rate) < 30mL/min/1.73 m2.
  5. Severely reduced liver function (Child-Pugh class C), especially severe obstructive hepatobiliary disease.
  6. Phaeochromocytoma
  7. Advanced cancer (with short/medium term prognosis).
  8. History of chest radiation therapy.
  9. Diabetic patients
  10. Severe valvular disease.
  11. Previous heart surgery.
  12. Left ventricular assist device (LVAD).
  13. Severe pulmonary disease.
  14. Hypersensitivity to any medicinal products containing gadolinium.
  15. Hypersensitivity to the active substance of the IMP or to any of the excipients.
  16. Contraindications to MRI, including implanted cardiac devices / pacemakers.
  17. Participants not able to follow instructions necessary to conduct the MRI.
  18. Women of childbearing potential.
  19. Participation in other clinical studies with investigational drugs either concurrently or within the last 30 days.
  20. Previous participation in this clinical trial
  21. History of ongoing drug abuse or alcoholism.
  22. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope, and possible impact of the trial
  23. Investigator site staff and sponsor directly involved in the conduct of the study and their family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Primary endpoint: Determination of the manganese uptake rate.

Secondary endpoints 2

  1. Efficacy: Difference in the uptake rate constant between healthy volunteers, HFpEF with HCM or CA.
  2. Safety: Frequency and severity of adverse events, injection site AEs, significant changes in vital signs, significant changes in ECG

Investigational products

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

Test 1

Anhydrous Mangafodipir Trisodium

SUB25422 · Substance

Active substance
Anhydrous Mangafodipir Trisodium
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS ADMINISTRATION
Max daily dose
0.05 mmol millimole(s)
Max total dose
0.05 mmol millimole(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Strength of the formerly approved product was 0.01 mmol/mL (50 mL vial); strength of the IMP is 0.058 mmol/mL (10 mL vial). The administered dose will be the same as the formerly approved product.

Auxiliary 1

Dotarem 279,3 mg/ml injeksjonsvæske, oppløsning

PRD355306 · Product

Active substance
Gadoteric Acid
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS USE
Max daily dose
0.2 mmol/kg millimole(s)/kilogram
Max total dose
0.2 mmol/kg millimole(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08CA02 — GADOTERIC ACID
Marketing authorisation
95-2155
MA holder
GUERBET
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IC Targets AS

Sponsor organisation
IC Targets AS
Address
Loerenveien 73 A
City
Oslo
Postcode
0585
Country
Norway

Scientific contact point

Organisation
IC Targets AS
Contact name
Clinical trial coordinator

Public contact point

Organisation
IC Targets AS
Contact name
Clinical trial coordinator

Third parties 1

OrganisationCity, countryDuties
Meddoc AS
ORL-000007587
 Sjetten, Norway On site monitoring, Code 10, Data management

Sponsor responsibilities

Article 77 compliance
IC Targets AS
Contact point sponsor
IC Targets AS
Article 77 implementation
IC Targets AS

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Norway Ended 42 1
Rest of world — 0 —

Investigational sites

Norway

1 site · Ended
Oslo University Hospital HF
Cardiology, Sognsvannsveien 20, 0372, Oslo

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2024-11-22 2025-11-29 2024-12-19 2025-06-30

Results and documents

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

Documents 6 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-508118-40-00_redacted 2.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Recruitment arrangements (for publication) K2_Recruitment material healthy volunteers_redacted 1
Subject information and informed consent form (for publication) L1_ICF_NO_redacted 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_EN_2023-508118-40-01 3.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_NO_2023-508118-40-01 3.0

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-06-13 Norway Acceptable
2024-09-20
 2024-09-20
2 NON SUBSTANTIAL MODIFICATION NSM-1 2025-01-14 Norway Acceptable
2024-09-20
 2025-01-14
3 NON SUBSTANTIAL MODIFICATION NSM-2 2025-05-06 Norway Acceptable
2024-09-20
 2025-05-06
4 SUBSTANTIAL MODIFICATION SM-4 2025-12-12 Norway Acceptable
2025-12-16
 2025-12-16

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