A Phase 1b Pharmacodynamic Study of VK0214 in Adrenomyeloneuropathy.
Research type
Research Study
Full title
Phase 1b, Multi-center, Randomized, Double-Blind, Placebo-Controlled, Rising Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of VK0214, in Subjects with the Adrenomyeloneuropathy Form (AMN) of X-linked Adrenoleukodystrophy (X-ALD).
IRAS ID
1005780
Contact name
Marianne Mancini
Contact email
Sponsor organisation
Viking Therapeutics Inc.
Eudract number
2022-000791-19
Clinicaltrials.gov Identifier
Research summary
A Phase 1b Pharmacodynamic Study of VK0214 in Adrenomyeloneuropathy.
Summary of Results
VK0214 is a novel, orally available thyroid hormone receptor beta agonist that is being evaluated as a potential treatment for X-linked adrenoleukodystrophy (X-ALD), a rare neurogenerative disease for which there are currently no pharmacologic treatment options. Like VK2809, VK0214 is also an orally available small molecule that is selective for the beta isoform of the thyroid hormone receptor.
X-ALD is a debilitating metabolic disorder that is caused by genetic mutations that disable the function of a peroxisomal transporter of very long chain fatty acids (VLCFAs). As a result, patients are unable to efficiently metabolize these acids, and their accumulation is believed to contribute to the onset and progression of X-ALD. Activation of the thyroid hormone receptor beta has been shown to increase the expression of an important compensatory VLCFA transporter, leading to improved metabolism and clearance of these compounds.
In the fourth quarter of 2024, Viking reported the results from a 28-day Phase 1b study of its small molecule drug candidate VK0214 in patients with X-ALD. The trial enrolled patients across three cohorts: placebo, and VK0214 doses of 20 mg and 40 mg daily. The primary objectives of the Phase 1b study were to evaluate the safety and tolerability of VK0214 in subjects with the adrenomyeloneuropathy (AMN) form of X-ALD, which is the most common form of the disease. An exploratory objective was to evaluate the effects of VK0214 on plasma levels of VLCFAs in this population. The results of this study showed that treatment with VK0214 resulted in significant reductions in mean VLCFA levels at both the 20 mg and 40 mg doses, compared to placebo. Plasma levels of the important 26 carbon very long chain fatty acid, a diagnostic biomarker, were reduced by approximately 38% relative to placebo (p<0.05).
In addition, subjects who received VK0214 experienced reductions in other important plasma lipids. Mean reductions relative to baseline and placebo were observed for LDL-C, apolipoprotein B, and lipoprotein (a) following 28 days of treatment. Importantly, VK0214 also demonstrated encouraging safety and tolerability, with treatment emergent adverse events generally reported as mild to moderate. The company plans to explore partnering opportunities for the further development of VK0214.
REC name
HSC REC A
REC reference
22/NI/0128
Date of REC Opinion
18 Nov 2022
REC opinion
Further Information Favourable Opinion