A Three Part, Randomized, Double-Blind, Placebo-Controlled, Phase I Study to evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of GXV-001 in Healthy Volunteers

Phase 1

Completed

• Conditions: Rett Syndrome; Fragile X Syndrome; Neurodevelopmental disorders; Neurological - Other neurological disorders; Mental Health - Other mental health disorders; Human Genetics and Inherited Disorders - Other human genetics and inherited disorders

• Registration Number: ACTRN12622000743763
• Lead Sponsor: GEXVal AU PTY LTD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-24
• Study Completion: 2024-01-26
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

Part A: Healthy volunteers will be included in Part A of the study if they satisfy all the following criteria:
1.Participants must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects;
2.Assessed to have a usual sleeping pattern that meets the following criteria as judged by the PI following discussion with the participant:
a.no use of sleep aids (homeopathic/natural remedies such as over-the-counter melatonin, valerian and sleep vitamins) during last 3 months,
b.generally regular bedtime between 10 pm and midnight,
c.generally regular wake up times between 6 am and 9 am,
d.sleep latency time usually no longer than 1 hour
e.generally, sleep duration of 6-10 hours per day.
3.Willingness to comply with a structured sleeping pattern for 7 days prior to drug administration and during all confinement periods with bedtime between 11 pm and 12 am and waketime between 7 am to 8 am each day and agree to abstain for exercise or exposure to excessive sunlight on the day of admission.
4.Based upon data from the actigraphy device worn continuously during the 7 days prior to Day -1, have bedtime confirmed to be between 11 pm and 12 am with waketime between 7am and 8am for at least 5 out of 7 nights with at least 2 sequential nights prior to Day -1.
5.Adult males and females between 18 to 40 years of age (inclusive) at screening;
6.Body Mass Index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight greater than or equal to 45 kg at screening;
7.Medically healthy without clinically significant abnormalities at screening, at Check-in on Day -1;
8.Female volunteers must:
a.Be of nonchildbearing potential i.e., be surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or be postmenopausal, where menopause is defined as 12 months of amenorrhea in the absence of other biological causes (females under the age of 50 years must have a documented serum follicle stimulating hormone (FSH) level > 40mIU/mL to confirm menopause);
b.If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), the participant:
•Must have a negative serum test at the screening visit and a negative urine pregnancy test within 24 hours prior to the start of study drug;
•Must not be breastfeeding, lactating, or planning pregnancy during the study period;
•Must agree not to attempt to become pregnant;
•If heterosexual and sexually active, agree to use double barrier contraceptives including non-hormonal containing IUD and one other additional barrier contraception (mandatory use of a condom by the male partner) after signing consent, during the study, and at least 35 days after the last dose of study drug (women in a same sex relationship do not need to use contraception)
•Must agree to not donate ova for at least 35 days after the last dose of study drug;
9.Male participants, if not surgically sterilized, must agree to:
a.Not donate sperm after signing consent, during the study, and at least 95 days after the last dose of study drug;
b.If engaging in sexual intercourse with a female partner who could become pregnant, use a condom in addition to having the female partner use a highly e

Exclusion Criteria

Part A: Healthy volunteers will be excluded from this study if there is evidence of any of the following at the screening visit, Check-in on Day -1 or prior to administration of the first dose on study Day 1:
1.History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant (participants with resolved childhood asthma may be included in the study)
a.Systolic blood pressure in the range of >140 mmHg and diastolic blood pressure in the range of >90 mmHg) after 5 minutes in semi-supine position at screening;
b.Heart rate in the range of >100 beats/min (inclusive) after 5 minutes rest in semi-supine position;
c.Body temperature (tympanic or oral), outside the range of 35.0°C and 37.5°C (inclusive);
d.The Screening 12-lead ECG outside the normal range (QTcF males less than or equal to 450 msec; females less than or equal to 470 msec) or with abnormalities, which are hazardous to the participant according to the opinion of the Investigator at screening;
e. Any clinically relevant findings in biochemistry, hematology, coagulation, and urinalysis examinations as judged by the Investigator at screening;
2.Any finding in the participant’s medical history, physical examination, or safety laboratory tests giving reasonable suspicion of disease that would contraindicate taking GXV-001, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrythmia;
3.People with or presenting a risk of intestinal disorders that can lead to obstruction of the digestive tract, including diverticula.
4.People with motility disorders of the gastrointestinal tract or gastrointestinal surgery.
5.People with known swallowing disorders.
6.Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications;
7.Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma);
8.Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia;
9.Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration (prior use of nasal sprays for hay fever may be permitted at the discretion of the PI);
10.History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia;
11.Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants;
12.Smokers, who smoked within the last 14 days and do not pass the urine cotinine test at screening

Study & Design

• Study Type: Interventional
• Study Design: Not specified