Treatment With 5-AminoLEvuliNic Acid Before Cardiac Surgery

NCT07027670 | Completed Phase 2 DMC

• 1 other identifier: 280513
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

TALEN is a prospective randomised double-blind placebo-controlled phase 2 study of 5-Aminolevulinic Acid with Sodium Ferrous Citrate (5-ALA-SFC) in adult patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). TALEN aims to identify the optimal biological dose (OBD) of 5-ALA-SFC.

Conditions

Cardiac Surgical Procedures; Coronary Artery Bypass; Aortic Valve Disease; Mitral Valve Disease

Keywords

heme oxygenase; cardiopulmonary bypass; HO-1; aortic valve replacement; mitral valve surgery; 5-aminolevulinic acid; delta aminolevulinic acid; sodium ferrous citrate

Outcome Measures

Primary Outcomes (2)

• Change from baseline HO-1 expression to time of cardiac surgery

  Normalised HO-1 expression in peripheral blood •Safety: Occurrence of adverse events / laboratory safety events defined as dose-limiting toxicity (DLTs)

  Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)

• Number of Participants With Dose Limiting Toxicity

  Up to 72 hours post-surgery

Secondary Outcomes (3)

• Incidence of treatment related emergent AEs [safety and tolerability]

  From time of administration of placebo or investigational medicinal product (IMP) (i.e. treatment-emergent AEs, TEAEs) to 72 hours post-operatively

• Change from baseline HO activity to time of cardiac surgery

  Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)

• Preliminary evaluation of the kinetics of peri-operative myocardial injury

  Serial measurements until 72 hours after release of aortic cross clamping

Study Arms (5)

Cohort 1

EXPERIMENTAL

75 mg 5-ALA with 118 mg SFC bd (lowest/starting dose) for three days before surgery (n=8 patients)

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA); Drug: Sodium ferrous citrate (SFC)

Cohort 2

EXPERIMENTAL

150 mg 5-ALA with 236 mg SFC or bd for three days before surgery (n=8 patients)

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA); Drug: Sodium ferrous citrate (SFC)

Cohort 3

EXPERIMENTAL

225 mg 5-ALA with 354 mg SFC bd for three days before surgery (n=8 patients)

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA); Drug: Sodium ferrous citrate (SFC)

Cohort 4

EXPERIMENTAL

300 mg 5-ALA with 472 mg SFC bd (maximum dose) for three days before surgery (n=8 patients)

Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA); Drug: Sodium ferrous citrate (SFC)

Placebo

PLACEBO COMPARATOR

2 patients in each cohort above will be allocated to placebo (n=8 patients in total across the study)

Other: Placebo

Interventions

5-Aminolevulinic Acid hydrochloride (5-ALA) DRUG

5-ALA: supplied for oral administration as a dark green, opaque, size 0, hypromellose (HPMC) capsule containing drug alone at a dosage strength of 75mg (58.7mg as 5-ALA). There are no excipients.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Placebo OTHER

Supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing 125mg lactose. The capsule shells are of non-animal origin, and are comprised of HPMC, titanium dioxide, and a copper complex of chlorophyllins.

Placebo

Sodium ferrous citrate (SFC) DRUG

SFC: supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing drug alone at a dosage strength 118mg (12.5mg as Fe). There are no excipients.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled for non-emergent cardiac surgery under CPB (including coronary artery bypass grafting, valve replacement, valve repair or a combination thereof)
• Signed informed consent
• Age ≥18 years
• Able and willing to comply with all study requirements

You may not qualify if:

• Female participants who are of childbearing potential who are either unable or unwilling to use highly effective contraception, or who are pregnant or breast feeding
• History of hypersensitivity to 5-ALA, SFC and/or porphyrins
• Acute or chronic types of porphyria
• Known genetic haemochromatosis or clinically significant iron overload
• History of clinically significant photosensitization
• Current long-term (\> 3 months) use of amiodarone
• Concomitant use of hypericin extract (including St John's Wort) or concomitant therapeutic dose oral iron replacement
• Use of other investigational medical product(s) \< 28 days prior to study or 5 half-lives, whichever is longer
• Cardiogenic shock/Low cardiac output syndrome requiring catecholamine infusion and/or mechanical circulatory support prior to induction of anaesthesia for cardiac surgery
• Recent acute myocardial infarction
• Cardiac surgery without cardiopulmonary bypass or induced fibrillating heart surgery
• Inadequate renal or liver function
• Any other condition which, in the opinion of the Investigator, makes the patient unsuitable for or may compromise their participation in the study

Sponsors & Collaborators

• University of Oxford: lead
• SBI Pharmaceuticals Co, Ltd.: collaborator
• Emerald Clinical Inc.: collaborator

Study Sites (1)

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Aortic Valve Disease

Interventions

Aminolevulinic Acid; ferrous citrate

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Arash Yavari, DPhil MRCP

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomisation will follow a sequential randomisation list prepared by the blinded trial statistician. As participants are randomised, they will be manually allocated the next available treatment kit (active or placebo) number from this list which will correspond to the randomisation number.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Sequential dose escalation cohorts of 10 evaluable patients each (8 on active:2 on placebo) dosed twice daily (bd) with 5-ALA-SFC or placebo for three pre-operative days and once on the day of cardiac surgery. Up to 4 discrete dose levels are anticipated.

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: June 18, 2025
• Study Start: February 1, 2021
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)