A Phase 1 Study of AV-380 in Healthy Subjects

NCT04815551 | Completed Phase 1 FDA Drug

• 1 other identifier: AV-380-20-101
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cachexia

Outcome Measures

Primary Outcomes (45)

• Assessment of adverse events (AEs) and treatment emergent adverse events (TEAEs)

  Through study completion, an average of 60 days

• Injection site safety and tolerability assessment

  Site injection tolerability will be assessed by the Investigator using a 4-level score (none, mild, moderate, severe) after IV infusion and SC injection.

  Visit Day 1

• Clinical laboratory measurements - Hematology - hemoglobin

  Hemoglobin (g/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Hematology - hematocrit

  Hematocrit (%)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Hematology - erythrocytes

  Erythrocytes

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Hematology - white blood cell count

  White blood cell count with differential (neutrophils, basophils, eosinophils, lymphocytes, monocytes and platelets) (X10(3)/UL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - sodium

  Sodium (mmol/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - potassium

  Potassium (mmol/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - calcium

  Calcium (mg/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - chloride

  Chloride (mmol/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - CO2

  CO2 (mmol/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - blood urea nitrogen

  Blood urea nitrogen (mg/dl)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - creatinine

  creatinine (mg/dL), glucose, total proteins, triglycerides, total cholesterol, AST, ALT, gamma-glutamyltransferase, creatinine phosphokinase, albumin, alkaline phosphatase, and total bilirubin

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - glucose

  Glucose (mg/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - total proteins

  Total proteins (g/dL), triglycerides, total cholesterol, AST, ALT, gamma-glutamyltransferase, creatinine phosphokinase, albumin, alkaline phosphatase, and total bilirubin

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - triglycerides

  Triglycerides (mg/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - total cholesterol

  Total cholesterol (mg/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - AST

  AST (U/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - ALT

  ALT (U/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - Gamma-glutamyltransferase

  Gamma-glutamyltransferase (U/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - Creatinine phosphokinase

  Creatinine phosphokinase (mg/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - albumin

  Albumin (g/dL)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - alkaline phosphatase

  Alkaline phosphatase (U/L)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Blood chemistry - total bilirubin

  Total bilirubin (mg/dl)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Coagulation - partial thromboplastin time

  Activated partial thromboplastin time (secs)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Coagulation - prothrombin time

  Prothrombin time (sec)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Coagulation - International normalized ratio

  International normalized ratio

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Hormonology

  Measured parameters: Hormonology (TSH, FSH (for post-menopausal women); β-HCG (for women of childbearing potential))

  Visits Day 1 through Day 90

• Clinical laboratory measurements - Hormonology - TSH

  TSH (mIU/mL)

  Visits Day 1 through Day 90

• Clinical laboratory measurements - Hormonology - FSH

  FSH (mIU/mL)

  Visits Day 1 through Day 90

• Clinical laboratory measurements - Urinalysis - pH

  pH

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Urinalysis - protein

  Protein (negative/positive)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Urinalysis - glucose

  Glucose (negative/positive)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Urinalysis - leukocytes

  Leukocytes (negative/positive)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Urinalysis - nitrites

  Nitrites (negative/positive)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Urinalysis - ketones

  Ketones (negative/positive)

  Visits Day 1 through Day 60

• Clinical laboratory measurements - Urinalysis - blood

  Blood (negative/positive)

  Visits Day 1 through Day 60

• Vital signs measurements - Blood pressure

  Supine and standing systolic and diastolic blood pressure (mmHg)

  Visits Day 1 through Day 90

• Vital signs measurements - Heart rate

  Heart rate (beats/min)

  Visits Day 1 through Day 90

• Vital signs measurements - Body temperature

  Body temperature (degrees Celsius)

  Visits Day 1 through Day 90

• Vital signs measurements - Respiratory rate

  Respiratory rate (breaths/min)

  Visits Day 1 through Day 90

• Electrocardiogram (ECG) measurements - Mean heart rate

  ECG mean heart rate (beats/min)

  Visits Day 1 through Day 90

• Electrocardiogram (ECG) measurements - PR interval

  PR interval, aggregate (msec)

  Visits Day 1 through Day 90

• Electrocardiogram (ECG) measurements - QRS axis

  QRS axis (deg)

  Visits Day 1 through Day 90

• Electrocardiogram (ECG) measurements - QTcF interval

  QTcF interval, aggregate (msec)

  Visits Day 1 through Day 90

Secondary Outcomes (7)

• Serum PK of single dose AV-380 via intravenous infusion and subcutaneous injection

  Visits Day 1 through D90

• Serum PK of single dose AV-380 via intravenous infusion and subcutaneous injection

  Visits Day 1 through Day 90

• To correlate the serum level of GDF-15 with the dose and serum level of AV-380

  Visits Day 1 through Day 90

• To correlate the serum level of GDF-15 with the dose and serum level of AV-380

  Visits Day 1 through Day 90

• To correlate the serum level of GDF-15 with the dose and serum level of AV-380

  Visits Day 1 through Day 90

Study Arms (8)

AV-380 IV 4 mg/kg

EXPERIMENTAL

IV infusion of AV-380 at dose level 4 mg/kg

Drug: AV-380

AV-380 IV 8 mg/kg

EXPERIMENTAL

IV infusion of AV-380 at dose level 8 mg/kg

Drug: AV-380

AV-380 IV 13 mg/kg

EXPERIMENTAL

IV infusion of AV-380 at dose level 13 mg/kg

Drug: AV-380

AV-380 IV 20 mg/kg

EXPERIMENTAL

IV infusion of AV-380 at dose level 20 mg/kg

Drug: AV-380

AV-380 SC 4 mg/kg

EXPERIMENTAL

Subcutaneous injection of AV-380 at dose level 4 mg/kg

Drug: AV-380

AV-380 SC 2 mg/kg

EXPERIMENTAL

Subcutaneous injection of AV-380 at dose level 2 mg/kg

Drug: AV-380

AV-380 SC 1 mg/kg

EXPERIMENTAL

Subcutaneous injection of AV-380 at dose level 1 mg/kg

Drug: AV-380

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AV-380 DRUG

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.

AV-380 IV 13 mg/kg; AV-380 IV 20 mg/kg; AV-380 IV 4 mg/kg; AV-380 IV 8 mg/kg; AV-380 SC 1 mg/kg; AV-380 SC 2 mg/kg; AV-380 SC 4 mg/kg

Placebo DRUG

Placebo is sterile liquid for IV infusion.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female volunteers, 18 to 50 years of age, inclusive.
• A body mass index (BMI) between 18 and 30 kg/m2 and weight between 60 and 90 kg.
• 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.
• Non-smoker or ex-smoker for longer than 6 months.
• 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.
• Able to sign and understand an ICF and able to comply with study restrictions prior to selection.

You may not qualify if:

• Presence or history of any disorder that may prevent the successful completion of the study.
• 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.
• Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational medicine product.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (1)

Biotrial Inc.

Newark, New Jersey, 07103, United States

Location

MeSH Terms

Conditions

Cachexia

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 25, 2021
• Study Start: February 22, 2021
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)