A Phase 1 Study of AV-380 in Healthy Subjects
A Phase 1 Study of AV-380 in Healthy Subjects
This double-blinded, placebo-controlled, single ascending dose (SAD) study is designed to
 evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity in
 healthy subjects of a single dose of AV-380. AV-380 is an immunoglobulin (Ig) G1 monoclonal
 antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15),
 a cytokine involved in cancer-induced cachexia.
Inclusion Criteria:

 1. Healthy male and female volunteers, 18 to 50 years of age, inclusive.

 2. A body mass index (BMI) between 18 and 30 kg/m2 and weight between 60 and 90 kg.

 3. Healthy as indicated by a comprehensive clinical assessment (detailed medical history
 and complete physical examination). Supine blood pressure (BP), heart rate (HR),
 electrocardiogram (ECG) intervals and routine laboratory tests within the normal range
 of the study center (see Appendix 4) or considered not clinically significant by the
 Investigator. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
 total bilirubin must be < 1.5 times the upper limit of the normal range (ULN). Total
 bilirubin, if above 1.5 x ULN, is only acceptable with a history of Gilbert's
 Syndrome.

 4. Non-smoker or ex-smoker for longer than 6 months.

 5. Sexually active pre-menopausal female subjects and female partners of male subjects
 must use adequate contraceptive measures, while on study and for at least 100 days
 after the IMP administration. Sexually active male subjects must use adequate
 contraceptive measures, while on study and for at least 160 days after the last dose
 of IMP. All fertile male and female subjects and their partners must agree to use a
 highly effective method of contraception. Effective birth control includes hormonal
 contraception (oral, intravaginal, transdermal, injectable or implantable),
 intrauterine device (IUD) plus one barrier method; or 2 barrier methods. Effective
 barrier methods are male or female condoms, diaphragms, and spermicides (creams or
 gels that contain a chemical to kill sperm). Vasectomy (at least 3 months before IMP
 administration) and vasectomized partner (provided that the partner is the sole sexual
 partner of the trial participant and that the absence of sperm in the ejaculate has
 been confirmed) are acceptable methods of contraception, as well as post-menopausal
 female for at least 1 year (confirmed with serum follicle stimulating hormone [FSH] >
 25.8 IU/L at screening), or surgically sterilized female subjects. Abstinence is not
 an acceptable contraception method. Female subjects who are of non-childbearing
 potential due to a surgical procedure or medical condition must provide documentation,
 and vasectomized male subjects must bring in the surgical report of the procedure.

 6. Able to sign and understand an ICF and able to comply with study restrictions prior to
 selection.

 Exclusion Criteria:

 1. Presence or history of any disorder that may prevent the successful completion of the
 study.

 2. Clinically significant abnormalities in laboratory test results (including hepatic and
 renal panels, complete blood count, chemistry panel and urinalysis), such as:

 -  White blood cell count < 3.0x109/L.

 -  Neutrophils < 1.5x109/L or clinically abnormal according to the subject's ethnic
 group (must be > 1.0x109/L for subjects of African descent).

 -  Hemoglobin < 10 g/dL.

 -  Platelet count < 125x109/L or > 450x109/L.

 -  ALT > 1.5 ULN.

 -  AST > 1.5 ULN.

 -  Total bilirubin > 1.5 ULN (except in the presence of Gilbert's syndrome).

 -  Creatinine > 1.2 ULN.

 -  Sodium < 132 mmol/L or > 147 mmol/L.

 -  Potassium < 3.2 mmol/L or > 5.5 mmol/L.

 -  Chloride < 93 mmol/L or > 111 mmol/L.

 -  Calcium < 8.3 mmol/L or > 10.7 mmol/L. Clinically significant abnormal values for
 all other laboratory parameters are at the investigator's discretion.

 3. Any surgical or medical condition that may interfere with the absorption,
 distribution, metabolism, or excretion of the investigational medicine product.

 4. Any history of drug related hypersensitivity reaction.

 5. Prior treatment with a monoclonal antibody.

 6. Intercurrent illness as evidenced by, e.g., nausea, vomiting, fever, or diarrhea)
 within 7 days before D1.

 7. History of drug abuse (habitual taking of addictive or illegal drugs) within 1 year
 before D1.

 8. Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or
 soda) or grapefruit-containing products or alcoholic beverages within 48 hours before
 D1 and until D7.

 9. Any condition or disease detected during the medical interview / physical examination
 that would render the subject unsuitable for the study, place the subject at undue
 risk or interfere with the ability of the subject to complete the study in the opinion
 of the Investigator or his designee.

 10. Frequent headaches and/or migraine, recurrent nausea and / or vomiting.

 11. Female subjects who are pregnant, or breastfeeding.

 12. Positive screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines,
 cannabinoids, cocaine, opiates, phencyclidine [PCP]) and breath alcohol test at
 screening or D-2.

 13. Positive serology for hepatitis B or hepatitis C or human immunodeficiency viruses
 (HIV).

 14. Positive SARS-CoV-2 RT-PCR.

 15. Any condition detected at screening that may interfere with or bias the physical
 examinations to be performed during the study.

 16. Any prescribed or over-the-counter medication or herbal products taken within 1 week
 prior to start of administration of IMP (D1) or within 6 times the elimination
 half-life of the medication prior to start of IMP intake (whichever is longer), except
 birth control as described in inclusion criterion number 5 in Section 6.1.
 Vitamin/mineral supplements and occasional use of acetaminophen is allowed up until 24
 hours before dosing.

 17. Participation in a clinical trial or use of an investigational drug within 30 days
 before randomization.

 18. Any vaccination within 30 days before signature of informed consent.