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.
TALEN is a prospective, randomised, double blind, placebo-controlled phase 2 study of 5-ALA-SFC administration in adults undergoing non-emergent cardiac surgery on CPB examining the potential of 5-ALA-SFC to induce haem oxygenase-1 (HO-1) as a novel cardio- and cyto-protective strategy for clinical benefit. 5-ALA is an amino acid found in several foods and a natural endogenous precursor in the synthesis of haem. Oral administration of 5-ALA-SFC has been shown to be safe and to induce a pharmacodynamic effect on the key effector, HO-1. TALEN is designed as a dose-finding trial with sequential dose cohorts, evaluating the safety, tolerability and PD response to 5-ALA-SFC to determine the optimum biological dose for further evaluation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
48
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.
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.
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.
John Radcliffe Hospital
Oxford, Oxfordshire, United Kingdom
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)
Time frame: Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
Number of Participants With Dose Limiting Toxicity
Time frame: Up to 72 hours post-surgery
Incidence of treatment related emergent AEs [safety and tolerability]
Treatment-related AEs assessed using CTCAE v5.0
Time frame: 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
HO enzyme activity
Time frame: 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
Cardiac troponin area under the curve for 72 hours
Time frame: Serial measurements until 72 hours after release of aortic cross clamping
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.