Part 1; Single ascending dose (main objective)• To investigate the safety and tolerability of single oral doses of VRG50635 in healthy adult subjectsPart 1; Single ascending dose (secondary objective)• To characterize the plasma and urine…
ID
Source
Brief title
Condition
- Spinal cord and nerve root disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1; Single ascending dose:
• Assessment of adverse events (AEs), vital signs, electrocardiograms (ECGs),
physical examinations, Columbia Suicide Severity Rating Scale (C-SSRS) and
laboratory safety tests
Part 2; Multiple ascending dose
• Assessment of AEs, vital signs, ECGs, physical examinations, C-SSRS and
laboratory safety tests
Secondary outcome
Part 1 Single ascending dose Food effect
•VRG50635 and VRG50468 measured by LC-MS/MS in plasma samples following single
oral doses of VRG50635. The pharmacokinetic parameters include: Tmax, tlag,
Cmax, AUC(0-last), AUC(0-inf) and T1/2
•Urine PK parameters: cumulative total amount excreted in urine and cumulative
percentage of dose in urine
Food Effect part 1
•PK of VRG50635 and VRG50468 following single oral dose to healthy adult
subjects in the fed and fasted states, based on the following parameters where
possible and appropriate: Tmax, tlag, Cmax, AUC(0-last), AUC(0-inf) and T1/2
Part 2; Multiple ascending dose
• VRG50635 and VRG50468 measured by LC-MS/MS in plasma samples and CSF
following multiple oral doses of VRG50635. The pharmacokinetic parameters
include: Tmax, tlag, Cmax, AUC(0-tau), Ctrough, Cavg, T1/2 and ARAUC
• VRG50635 and VRG50468 concentrations measured by LC-MS/MS in CSF and
plasma/CSF ratio
Background summary
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that
results from the loss of motor neurons in the brain and spinal cord causing
paralysis of voluntary muscles. Like most neurodegenerative disorders, ALS is
thought to be caused by abnormal protein aggregation and the perturbation of
the autophagy pathway that is neuroprotective and essential for synaptic
plasticity, glial neuroinflammation, oligodendrocyte development, and
neurogenesis in the brain. Thus, repair and/or preservation of the integrity of
the neuronal protein quality control system is an attractive and emerging
therapeutic target.
Verge has identified VRG50635 which is hypothesized in improving motor neuron
health and survival, has exposures in the central nervous system (CNS), has
effects on relevant target, pathway, and disease biomarkers supporting
translatability, and has a favorable safety profile in non-human models.
Furthermore, VRG50468 can reduce ALS patient motor neuron death in vitro across
multiple genetic subtypes with efficacy that surpasses current approved ALS
drugs.
Study objective
Part 1; Single ascending dose (main objective)
• To investigate the safety and tolerability of single oral doses of VRG50635
in healthy adult subjects
Part 1; Single ascending dose (secondary objective)
• To characterize the plasma and urine pharmacokinetic (PK) profile of Prodrug
VRG50635 and Parent VRG50468 following single oral doses of VRG-50635 in
healthy adult subjects
Part 1 Single ascending dose Food effect (secondary objective)
• To characterize the effect of food (high fat meal) on the plasma PK of
Prodrug VRG50635 and Parent VRG50468 following a single oral dose of VRG50635
in the fed state, when administered to healthy adult subjects
Part 2; Multiple ascending dose (main objective)
• To investigate the safety and tolerability of multiple oral doses of VRG50635
in healthy adult subjects
Study design
This is a two-part first in human, single centre, randomized, double blind,
placebo-controlled, parallel group, dose-ranging study in healthy subjects
(parts 1 and 2) to investigate the safety, tolerability, pharmacokinetics and
target engagement of VRG50635.
Intervention
VRG50635 or placebo oral administration of capsules
Part 1: single dose of VRG50635 or placebo (Food effect cohort 3 : 2 single
doses of VRG50635 or placebo)
Part 2: multiple dose of VRG50635 or placebo
Study burden and risks
For this first-in-human study, the population will be healthy volunteers.
Two Tower Place, Suite 950
South San Francisco 94080
US
Two Tower Place, Suite 950
South San Francisco 94080
US
Listed location countries
Age
Inclusion criteria
Inclusion criteria - Parts 1 and 2
1. Healthy male or female between 18 to 65 years of age at screening
(inclusive).
4. For male and female subjects of childbearing potential: Subjects and their
spouse/partners who are of childbearing potential must use highly effective
contraception when engaging in sexual activity consisting of 2 forms of birth
control (1 of which must be a barrier method such as latex or polyurethane
condoms) starting at screening and continue throughout the clinical study
period, and for 90 days after the final study drug administration.
5. For males: Subject must not donate sperm starting at screening and
throughout the clinical study period, and for 90 days after the final study
drug administration.
Exclusion criteria
Exclusion criteria - Parts 1 and 2
1. History of clinically significant hematological, renal, neurologic,
pancreatic, gastrointestinal, hepatic, cardiovascular, psychological,
pulmonary, metabolic, endocrine, immunological, allergic disease, or other
major disorders.
2. Current significant medical or psychiatric condition.
4. Evidence of clinically significant hepatic or renal impairment in the
opinion of the investigator, including alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) >1.5 the upper limit of normal (ULN) or
bilirubin > 1.5 ULN. Patients with Gilbert syndrome without evidence of hepatic
impairment may be enrolled.
14. Poor peripheral venous access.
21. A lifetime history of suicidal behavior or suicidal ideation as determined
by a positive response (**Yes**) to either question 4 or question 5 of the
C-SSRS at screening.
26. For part 2 only: Subjects not eligible for lumbar puncture
(anti-coagulation, anti-aggregation or blood coagulation pathologies, recent
spine surgery, acquired or congenital spine malformation, clinical signs of
intracranial hypertension, cutaneous infection at the punction site)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-002747-22-NL |
| CCMO | NL81735.056.22 |
| Other | T.b.d. |