Alzheimer Disease
Conditions
Brief summary
ASN51-101 is a randomized, double-blind, placebo-controlled, phase 1 first in human (FIH) safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) study of oral ASN51 in healthy young adult and elderly subjects and elderly subjects with AD. The study is comprised of three parts (Part 1, Part 2, and Part 3).
Detailed description
Part 1: Five (5) single-ascending oral doses will be administered to 40 healthy adult male or female subjects (aged 18-55 years, inclusive). Escalation to the next higher dose level may occur only after evaluation of the safety and PK results of the previous dose level (at least 6 evaluable subjects). Within each cohort, 6 subjects will receive one dose of ASN51, and 2 subjects will receive one dose of matching placebo. Based on this interim safety evaluation, dose levels may be revised. Part 2: Multiple ascending oral doses will be administered to 24 healthy elderly subjects (aged 55 - 80 years, inclusive) in 3 sequential dosing groups (8 subjects in each dosing group). Six (6) subjects will receive ASN51 and two (2) subjects will receive matching placebo in each dosing group (cohort) for 10 days. Escalation to the next higher dose level may occur only after evaluation of the safety and PK results of the previous dose level (at least 6 evaluable subjects). Based on this interim safety evaluation, dose levels may be revised. Treatment of the subjects of each cohort will be administered as follows: Day 1 - 9: Twice daily (BID) dosing (or once daily (QD) dosing); to be defined after Part 1 (SAD) of ASN51 or placebo. Day 10: Only one dose will be administered in the morning of Day 10 Selection of the dosing regimen and dose levels to be administered in Part 2 will be made by the safety review committee (SRC), depending on the results of Part 1. Part 3: Multiple oral doses will be administered to 12 AD subjects (aged 55-85, inclusive) in a single dosing group for 10 days. Eight (8) AD subjects will receive ASN51 and four (4) AD subjects will receive placebo in that dosing group (cohort). Selection of the dose level to be administered in Part 3 will be made by the SRC and will depend on the results of study Part 1 (SAD) and Part 2 (MAD), and will be below the maximum tolerated dose administered to healthy subjects in Part 2. Treatment of the AD subjects will be administered as follows: Day 1 - 9: Twice daily (BID) dosing (or once daily (QD) dosing); to be defined after Part 2 (MAD) of ASN51 or placebo. Day 10: Only one dose will be administered in the morning of Day 10. Selection of the dosing regimen and dose level to be administered in Part 3 will be made by the safety review committee (SRC), depending on the results of both Part 1 and Part 2.
Interventions
DRUGASN51
ASN51 formulation for oral capsule
DRUGPlacebo
Placebo formulation for oral capsule
Sponsors
Asceneuron S.A.
Neuroscience Trials Australia
Asceneuron Pty Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1 and Part 2 Only: Inclusion Criteria: 1. Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if, in the opinion of the Investigator, the finding is (a) unlikely to introduce additional risk to the subject, (b) will not interfere with study procedures or confound study results, and (c) is not otherwise exclusionary (see
Exclusion criteria
). 2. Men and women aged 18-55 years, inclusive, at Screening (Part 1) or 55-80 years, inclusive, at Screening (Part 2) 3. Subject must understand the nature of the study and provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures. 4. Able to complete all study related testing and evaluations 5. Women (Part 1 only) and men of child-bearing potential with partners of child-bearing potential must agree to use highly effective contraception. Contraception should consist of: (1) a condom for the male participant or partner of a female participant, combined with (2) a highly effective method of contraception (e.g., a hormonal method associated with suppression of ovulation, an intrauterine device \[IUD\]) for the female participant or partner of a male participant. Abstinence from heterosexual intercourse should only be used in place of contraception when this is consistent with the usual and preferred lifestyle of the participant. For male subjects, contraception should continue for 90 days after the last dose of investigational medicinal product (IMP, one spermatic cycle). Male subjects should agree to refrain from sperm donation throughout this same period. 6. Women of non-childbearing potential must be post-menopausal (the last menstrual period was at least 12 months ago, and follicle-stimulating hormone \[FSH\] at Screening confirms post-menopausal status), or have no uterus, ovaries, or fallopian tubes (or have their fallopian tubes tied). All women must have a negative pregnancy test result before administration of test article. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound. 7. Body weight \> 50.0 kg for men and \> 50 kg for women and Body Mass Index (BMI) within the range 18.5-30.0 kg/m2, inclusive. 8. Subject must be, in the opinion of the Investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant. 9. Subjects is fluent in the local language. 10. Subject agrees not to post any personal medical data related to the study or information related to the study on any website or social media site (e.g., Facebook, Twitter, etc.) until the trial has been completed, this does not include information about participating in a clinical study in general. 11. \[Part 2 only\] Subject is able to undergo Lumbar Puncture (LP)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 38 days |
Secondary
| Measure | Time frame |
|---|---|
| PK parameter: The area under the concentration-time curve from zero to infinity (AUC0-inf) in plasma | Up to 10 days |
| PK parameter: The maximum concentration (Cmax) at steady state in plasma | Up to 10 days |
| PK parameter: The time to reach maximum concentration (tmax) in plasma | Up to 10 days |
| PK parameter: The terminal elimination rate constant (λZ) with the respective half-life (t½) in plasma | Up to 10 days |
| PK parameter: The percentage of the extrapolated AUC in plasma | Up to 10 days |
| PK parameter: Area under the concentration-time curve from time zero to the end of the dosing interval (AUCtau) in plasma (Part 2 Day 1 only) | Up to 1 day |
| PK parameter: The minimal observed trough concentration (Cmin) at steady state in plasma | Up to 10 days |
| PK parameter: The average concentration (Cavg) at steady state in plasma | Up to 10 days |
| PK parameter: Accumulation Ratio: AUCtau at Day 10/ AUCtau at Day 1 in plasma | Up to 10 days |
| PK parameter: The area under the concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t) in plasma | Up to 10 days |
| PK parameter: The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t) in cerebrospinal fluid (CSF) | Up to 10 days |
| PK parameter: The area under the plasma concentration-time curve from zero to infinity (AUC0-∞) in CSF | Up to 10 days |
| PK Parameter: The maximum plasma concentration (Cmax) in CSF | Up to 10 days |
| PK parameter: The time to reach maximum plasma concentration (tmax) in CSF | Up to 10 days |
| PK parameter: The terminal elimination rate constant (λZ) with the respective half-life (t½) in CSF | Up to 10 days |
| PK parameter: The percentage of the extrapolated AUC in CSF | Up to 10 days |
| PK parameter: Area under the concentration-time curve from time zero to the end of the dosing interval (AUCtau) in CSF | Up to 10 days |
| PD parameter: Change from baseline in total and phosphorylated CSF tau | Up to 10 days |
| PD parameter: Change from baseline in quantitative electroencephalography power and the P300 event related potential (ERP) | Up to 10 days |
| PK parameter: The mean cumulative amounts excreted (both in % of the administered dose and in mg ASN51) will be calculated both for Fe(0-72h) and Fe(0-tau) and Ae(0-72h) and Ae(0-tau), respectively | Up to 10 days |
Countries
Australia
Outcome results
None listed