Primary objective:To assess the safety and tolerability of single doses of i.v. administered NX210.Secondary objective:To assess the PK of NX210 via its metabolite NX210c in plasma after single doses of i.v. administered NX210.Exploratory objectives…
ID
Source
Brief title
Condition
- Spinal cord and nerve root disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following are defined as safety/tolerability parameters:
Physical examination;
(Serious) adverse events (SAEs and AEs);
Clinical laboratory assessments including hematology, biochemistry and
urinalysis;
12-lead ECG;
Telemetry;
Vital signs;
Local tolerability.
The following are defined as PK plasma parameters for NX210 via its metabolite
NX210c (calculated using a non-compartmental model):
Maximum concentration (Cmax);
Time to Cmax (tmax);
Terminal elimination rate constant (Kel);
Terminal elimination half-life (t1/2);
Area under the concentration-time curve (AUC) from time of dosing (zero) to
time t of the last measured concentration above the limit of quantification
(AUC0-t);
AUC under the concentration-time curve from time zero to infinity (AUC0-inf);
Total clearance (CL);
Volume of distribution (Vz).
Secondary outcome
Nap
Background summary
NX210 is a chemically synthesized peptide of 12 natural amino acids derived
from SubCommissural Organ (SCO)-spondin. SCO-spondin is a large multi-domain
glycoprotein of 4.500 amino acids, specific to the Central Nervous System (CNS)
extracellular matrix (ECM) and secreted by specialized ependymocytes located in
the SCO, a highly conserved structure located in the roof of the third brain
ventricle of all vertebrates [1].
NX210 targets to diseases belonging to CNS dysfunctions, like traumatic spinal
cord injury (SCI), or memory loss/cognitive disorders.
NX210 preclinical data demonstrated efficacy in 2 animal models of SCI and
cognitive impairment in IP route, which can be transposed to the intravenous
(i.v.) route in human.
Although NX210 precise mechanism of action is still under investigation,
preclinical data showed that NX210 has properties usually looked for human
treatment of any neurological disorder, i.e. neuroprotection,
neuroregeneration, remodeling and cellular plasticity mechanisms induction, or
reduction in inflammation, mainly in intraperitoneal (IP) route.
Study objective
Primary objective:
To assess the safety and tolerability of single doses of i.v. administered
NX210.
Secondary objective:
To assess the PK of NX210 via its metabolite NX210c in plasma after single
doses of i.v. administered NX210.
Exploratory objectives:
To assess the PD of NX210 by analyzing biomarkers and exploring the
neurophysiological effects of NX210 on electroencephalography (EEG) after
single doses of i.v. administered NX210.
To assess the PK/PD relationship of NX210 after single doses of i.v.
administered NX210.
To assess potential anti-drug antibodies after single doses of i.v.
administered NX210.
Study design
Single site, randomized, placebo-controlled, double-blind, single ascending
dose study in healthy male and female subjects.
Intervention
Five (5) single ascending doses of NX210 are planned to be tested in 5 cohorts
of 8 healthy subjects each. In each cohort, subjects will be randomized in a
3:1 fashion to NX210 or placebo.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further
information.
Avenue Rockefeller 60
Lyon 69008
FR
Avenue Rockefeller 60
Lyon 69008
FR
Listed location countries
Age
Inclusion criteria
Subject is a male or is a female of non-childbearing potential, aged between 18
and 55 years (inclusive).
A body weight of >=50.0 kg and <=90.0 kg (85.0 kg for Cohort 5 at the highest
dose) and a body mass index (BMI) of >=18.0 kg/m2 and <=30.0 kg/m2 at Screening.
Healthy as determined by the Investigator, based upon a medical evaluation
including medical history, physical examination, neurological examination, lab
tests and ECG performed at screening.
Subjects understand the study, can give written informed consent at Screening,
and are willing to comply with the requirements and restrictions of the study.
Exclusion criteria
Prior or ongoing medical condition, medical history, physical findings, ECG
findings, laboratory or vital signs abnormality that, in the Investigator's
opinion, could adversely affect the safety of the subject.
The subject has a current or recurrent disease (e.g., cardiovascular,renal,
liver, gastrointestinal, malignancy or other conditions) that could affect the
distribution, metabolism or excretion of the investigational product or could
affect clinical or laboratory assessments.
History of any clinically significant allergy, hypersensitivity or intolerance.
Subject with one or more of the following laboratory abnormalities at Screening
and between Screening and dosing: abnormal Alanine aminotransferase (AST),
abnormal aspartate aminotransferase (ALT) or abnormal alkaline phosphatase
levels (ALP) >=1.5 x upper limit of normal (ULN); total bilirubin >=1.5 x ULN; or
clinically significant laboratory abnormalities or abnormalities which are
deemed to interfere with the ability to interpret study data. A repeat is
allowed once to determine eligibility.
Design
Recruitment
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 | EUCTR2020-000859-12-NL |
| CCMO | NL73571.056.20 |