Part 1 SAD:Primary objective: To evaluate the safety and tolerability of single ascending doses of ANXV in healthy subjects.Secondary objective: To determine the PK profile of single ascending doses of ANXV in healthy subjects.Part 2 MAD:Primary…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part I:
Frequency, intensity and seriousness of adverse events (AEs)
Clinically significant changes in:
-ECG
-Telemetric recordings
-Vital signs (blood pressure, pulse, body temperature, respiratory rate, pulse
oximetry)
-Safety laboratory parameters
-Physical examinations
Incidence and titre of ADA to ANXV
Part II:
Frequency, intensity and seriousness of AEs
Clinically significant changes in:
-ECG
-Telemetric recordings
-Vital signs (blood pressure, pulse, body temperature, respiratory rate, pulse
oximetry)
-Safety laboratory parameters
-Physical examinations
Incidence and titre of ADA to ANXV
Secondary outcome
Part I:
PK parameters (will be calculated if sufficient data are available):
-Area under the plasma concentration vs time curve from time zero extrapolated
to infinity (AUCinf)
-AUC from time zero to time of last quantifiable analyte concentration (AUClast)
-Observed maximum concentration (Cmax)
-Time to Cmax (Tmax)
-Terminal slope of a semi-logarithmic concentration-time curve (*z)
-Terminal half life (T*)
-Clearance (CL)
-Volume of distribution (Vz)
-Dose proportionality after a single dose, based on AUC and Cmax
-Fraction excreted in urine (fe)
Part II:
PK parameters after first dose (will be calculated if sufficient data are
available):
-AUClast
-Cmax
-Tmax
-*z
-T*
-CL
-Vz
-Dose proportionality
- Fraction excreted in urine (fe) (only cohort 3)
PK parameters after last dose:
-AUC during a dosage interval (tau) (AUCtau)
-Cmax
-Tmax
-*z
-T*
-CL
-Vz
-Vss
-Dose proportionality after multiple doses, based on AUC at steady state
(AUCtau) and Cmax
-Accumulation ratio
-Minimum plasma concentrations of ANXV on Day 5 (Cmin)
-Mean plasma concentrations of ANXV on Day 5 (Cmean)- Fraction excreted in urine (fe) (only cohort 3)
Background summary
ANXV is in development as a potential first-line treatment for patients with
retinal vein occlusion (RVO). RVO is a debilitating, sight-threatening disease
caused by an occlusion of the retinal vein. No registered treatment for acute
resolution of RVO is available and there is a high unmet medical need to
improve the blood flow to retina in the acute setting prior to the emergence of
complications.
The proposed drug product ANXV contains human protein Annexin A5 produced by
recombinant techniques in Escherischia Coli. As the endogenous Annexin A5, the
recombinant protein specifically binds to a negative
phospholipid-phosphatidylserine (PS) on cell membranes. ANXV ability to bind to
PS has been confirmed by the Sponsor in vitro.
PS has been recently identified as a key molecule on RVO patients erythrocytes
that is involved in formation of the retinal vein occlusion. On the basis of in
vitro, ex vivo and in vivo pharmacology results, ANXV is expected to rapidly
and focally bind to PS-carrying erythrocyte membranes, interfere with
PS-dependent adherent cell-to-cell interactions at the site of occlusion,
reduce the size of or remove the occlusive aggregate. Thus, ANXV holds
potential to rapidly improve retinal blood supply, reduce the risk of blindness
and provide other short-term and long-term benefits for RVO patients treated in
the acute setting (as soon as possible after the diagnosis) and prior to the
emergence of complications.
Study objective
Part 1 SAD:
Primary objective: To evaluate the safety and tolerability of single ascending
doses of ANXV in healthy subjects.
Secondary objective: To determine the PK profile of single ascending doses of
ANXV in healthy subjects.
Part 2 MAD:
Primary objective: To evaluate the safety and tolerability of multiple
ascending doses of ANXV in healthy subjects.
Secondary objectives: To determine the PK profile of multiple ascending doses
of ANXV in healthy subjects.
Study design
This is an adaptive, randomised, double-blind, single-centre,
placebo-controlled phase I, first-in-human (FIH) study designed to evaluate the
safety, tolerability and pharmacokinetics (PK) of single and multiple
intravenous dosing of ANXV in healthy male subjects.
This study is divided in 2 parts. Part I, Single Ascending Dose (SAD), will
explore safety, tolerability and PK of single intravenous doses of ANXV. Part
II, Multiple Ascending Dose (MAD), will explore safety, tolerability and PK of
multiple intravenous doses of ANXV.
See section 9 of the CSP.
Intervention
intravenous doses of ANXV 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.
Norrtullsgatan 6 Norrtullsgatan 6
Stockholm 11329
SE
Norrtullsgatan 6 Norrtullsgatan 6
Stockholm 11329
SE
Listed location countries
Age
Inclusion criteria
Willing and able to give written informed consent for participation in the
study.
Healthy male subject aged 18-60 years inclusive.
Body Mass Index (BMI) >= 18.0 and <= 30.0 kg/m2 and weight at least 50 kg and no
more than 100 kg at screening.
Overtly healthy based on medical history, physical findings, vital signs, ECG
and laboratory values at the time of screening, as judged by the Investigator.
Male subjects must be willing to use condom or be vasectomised or practice
sexual abstinence to prevent pregnancy and drug exposure of a partner, and
refrain from donating sperm from the date of dosing until 3 months after (last)
dosing with the IMP.
Their female partner of child-bearing potential are expected to use
contraceptive methods with a failure rate of < 1% to prevent pregnancy
(combined [oestrogen and progestogen containing] hormonal contraception
associated with inhibition of ovulation [oral, intravaginal, transdermal],
progestogen-only hormonal contraception associated with inhibition of ovulation
[oral, injectable, implantable], intrauterine device [IUD] or intrauterine
hormone-releasing system [IUS]).
Exclusion criteria
History of any clinically significant disease or disorder which, in the opinion
of the Investigator, may either put the subject at risk because of
participation in the study, or influence the results or the subject*s ability
to participate in the study.
Any clinically significant illness, medical/surgical procedure or trauma within
4 weeks of the first administration of IMP.
Malignancy within the past 5 years with the exception of in situ removal of
basal cell carcinoma.
Any planned major surgery within the duration of the study.
Any positive result on screening for serum hepatitis B surface antigen (HbsAg),
hepatitis C antibody and Human Immunodeficiency Virus (HIV).
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 | EUCTR2020-004361-39-NL |
| CCMO | NL75226.056.20 |