Healthy Volunteers
Conditions
Keywords
Healthy volunteers, Monoclonal antibody, AV-1, Safety, Dengue
Brief summary
AV-1 is a human monoclonal antibody (mAb) being investigated as a potential therapy for dengue, a mosquito-borne viral disease with extensive global public health impact. Globally, over 2 billion people are thought to be at risk of infection from the dengue virus and there are an estimated 390 million infections each year. Current treatment options for dengue are limited to supportive care, so a safe and effective treatment would provide substantial public health benefits. AV-1 has not previously been tested in humans. This study aims to determine the safety of AV-1 in healthy adult volunteers, when administered as a single IV infusion. The results of the study are based on the clinical study report and statistical analysis plan.
Interventions
DRUGAV-1
Single dose, administered by IV infusion (volume: 250 mL)
DRUGPlacebo
0.9% sterile saline. Administered by IV infusion (volume: 250 mL)
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
AbViro LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be in good health at Screening (reaffirmed at Check-in): 1. Good health is defined by the absence of a medical condition described in the
Exclusion criteria
of the study protocol, and based on screening medical history, physical examination, vital signs, and 12-lead electrocardiogram (ECG). 2. If the subject has another current, ongoing chronic medical condition, the condition cannot: (i) Be first diagnosed within 3 months of enrollment; or (ii) Be a pre-existing medical condition that is not exclusionary but has worsened in terms of clinical outcome within 3 months of enrollment; or (iii) Involve the need for medication that may pose a risk to the subject's safety or impede assessment of adverse events (AEs) or anti-AV-1 antibody response if they participate in the study. * Women who are not pregnant and/or not lactating. * Female subjects, including postmenopausal women and surgically sterile women, must have a negative serum pregnancy test at Screening, Check-in and on admission to the study facility. * Female subjects must fulfill one of the following criteria: 1. Postmenopausal women must have had ≥ 12 months of spontaneous amenorrhea with follicle-stimulating hormone concentration consistently ≥40 mIU/mL and must have a negative pregnancy test result at Screening and Check-in. 2. Surgically sterile women - those who have had a hysterectomy, bilateral ovariectomy (oophorectomy), or bilateral tubal ligation, must provide documentation of the procedure and must have a negative pregnancy test at Screening and Check-in. 3. Must be willing to not engage in sexual intercourse from Check-in until the final follow-up visit on Day 120 (± 5 days). 4. Must be willing to use an acceptable method of birth control until the final follow-up visit on Day 120 (± 5 days) as defined by the protocol and Investigator. * Male subjects who are biologically capable of fathering children must agree and commit to using an adequate form of double-barrier contraception, and refrain from sperm donation from Check-in until the final follow-up visit on Day 120 (± 5 days). A male subject is considered capable of fathering children even if his sexual partner is sterile or using contraceptives. * Body Mass Index between 18.5 and 29.9 kg/m\^2 inclusive. * Must not have traveled outside the USA within 60 days prior to Check-in, and agree not to travel outside the USA through the final follow-up visit on Day 120 (± 5 days). * Must agree to abide by study restrictions and be willing to sign an informed consent form (ICF).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Baseline up to Day 120 (± 5 days) | Clinical laboratory abnormalities reported as TEAEs by the investigator. Clinical laboratory abnormalities were defined as any abnormal findings in analysis of hematology, serum chemistry, coagulation, and urine parameters. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related. |
| Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Baseline up to Day 120 (± 5 days) | A full physical examination included examination of skin; head, ears, eyes, nose, throat (HEENT); neck; thyroid; lungs; heart; cardiovascular; abdomen; lymph nodes; and musculoskeletal system/extremities. Focused examination included lungs, cardiovascular, abdomen, and skin. Investigator could perform targeted, symptom-directed physical examination. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related. |
| Number of Participants With Vital Sign Abnormalities Reported as TEAEs | Baseline up to Day 120 (± 5 days) | Vital sign measurements included systolic and diastolic blood pressure, oral body temperature, heart rate, and respiratory rate. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related. |
| Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | Baseline up to Day 120 (± 5 days) | Number of participants with abnormal 12-lead ECG reported as a TEAE of electrocardiogram QT prolonged by the investigator. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related. |
| Number of Participants With TEAEs | Baseline up to Day 120 (± 5 days) | An adverse event (AE) was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure. |
| Number of Participants With Serious Adverse Events (SAEs) | Baseline up to Day 120 (± 5 days) | An AE or suspected adverse reaction was considered an SAE if, in the view of either the Investigator or Sponsor, it resulted in any of the following outcome: * Death * A life-threatening AE * Inpatient hospitalization or prolongation of existing hospitalization * a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * A congenital anomaly/birth defect Important medical events that did not result in death, was life-threatening, or required hospitalizations could have been considered serious when, based upon appropriate medical judgment, they jeopardized the participant and required medical or surgical intervention to prevent one of the outcomes listed in this definition. |
| Number of Participants by Severity of AEs | Baseline up to Day 120 (± 5 days) | AEs were assessed by the Investigator as Mild (Grade 1), Moderate (Grade 2), or Severe (Grade 3). Mild (Grade 1): Events that were transient and required only minimal or no treatment or therapeutic intervention and did not interfere with the participants usual activities of daily living. Moderate (Grade 2): Events that were alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but posed no significant or permanent risk of harm to the participant. Severe (Grade 3): Events interrupted usual activities of daily living, or significantly affected clinical status, or required intensive therapeutic intervention. Severe events were usually incapacitating. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of Distribution During the Terminal Phase (Vz) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | Volume of distribution during the terminal phase was calculated as dose divided by (AUC0-infinity\*λz). |
| Apparent Terminal Half-life (t1/2) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | t1/2 is defined as terminal half-life, calculated as: ln(2)/ λz, where λz is apparent terminal elimination rate constant. |
| Number of Participants With Detectable Anti-AV-1 Antibody | Baseline, Days 29 (±2), 85 (±5), and 120 (±5) | Serum samples for measurement of anti-AV-1 antibody levels were analyzed by a validated electrochemiluminescence enzyme-linked immunosorbent assay method used for detection and confirmation of pre-existing and treatment-emergent anti-AV-1 antibodies in serum samples based on the MesoScale Discovery platform that utilized labeled AV-1 for detection of anti-AV-1 antibodies and treatment-emergent antibodies. Number of participants with detectable anti-AV-1 antibody |
| Total Serum Clearance (CL) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | Total serum clearance was calculated as dose divided by AUC0-infinity. |
| Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | AUC0-infinity was calculated as: AUC from time 0 to the last quantifiable concentration (AUC0-tlast) + (last observed serum drug concentration \[Ct\] / Apparent terminal elimination rate constant \[λz\]). |
| AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion | AUC0-48 was calculated using the linear trapezoidal rule method. |
| AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | AUC0-tlast was calculated using the linear trapezoidal method. |
| Maximum Observed Serum Concentration (Cmax) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | Cmax is defined as maximum observed serum drug concentration. |
| Time to Reach Cmax (Tmax) of AV-1 | Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120 | Tmax is defined as Time to reach maximum serum concentration following drug administration. |
Countries
United States
Participant flow
Recruitment details
This was a single-center study conducted in the United States.
Pre-assignment details
On the first day of dosing in all cohorts, the first group in each cohort comprised 2 sentinel participants: 1 was randomly assigned to receive AV-1 and the other was randomly assigned to receive placebo. After the Investigator reviewed the safety data from the 72-hour post-dose period for the sentinel participants, the remainder of the cohort (5 participants randomly assigned to AV-1; 1 participant randomly assigned to placebo) were dosed at least 72 hours after the sentinel participants.
Participants by arm
| Arm | Count |
|---|---|
| AV-1 30 mg Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 30 mg (volume: 250 mL) on Day 1. | 6 |
| AV-1 90 mg Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 90 mg (volume: 250 mL) on Day 1. | 6 |
| AV-1 250 mg Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 250 mg (volume: 250 mL) on Day 1. | 6 |
| AV-1 500 mg Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 500 mg (volume: 250 mL) on Day 1. | 6 |
| AV-1 1000 mg Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 1000 mg (volume: 250 mL) on Day 1. | 7 |
| Placebo Participants received a single IV infusion (infusion duration: 1 hour) of placebo (volume: 250 mL) on Day 1. | 11 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Participant non-compliance | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Positive urine drug screen | 1 | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | AV-1 30 mg | AV-1 90 mg | AV-1 250 mg | AV-1 500 mg | AV-1 1000 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 44.7 years STANDARD_DEVIATION 6.89 | 35.0 years STANDARD_DEVIATION 9.65 | 35.0 years STANDARD_DEVIATION 9.72 | 32.3 years STANDARD_DEVIATION 8.29 | 37.0 years STANDARD_DEVIATION 13.52 | 35.4 years STANDARD_DEVIATION 10.5 | 36.4 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 5 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 5 Participants | 2 Participants | 4 Participants | 6 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 6 Participants | 8 Participants | 31 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 6 Participants | 25 Participants |
| Sex: Female, Male Male | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 11 |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 0 / 6 | 1 / 6 | 4 / 7 | 3 / 11 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 11 |
Outcome results
Primary
Number of Participants by Severity of AEs
AEs were assessed by the Investigator as Mild (Grade 1), Moderate (Grade 2), or Severe (Grade 3). Mild (Grade 1): Events that were transient and required only minimal or no treatment or therapeutic intervention and did not interfere with the participants usual activities of daily living. Moderate (Grade 2): Events that were alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but posed no significant or permanent risk of harm to the participant. Severe (Grade 3): Events interrupted usual activities of daily living, or significantly affected clinical status, or required intensive therapeutic intervention. Severe events were usually incapacitating.
Time frame: Baseline up to Day 120 (± 5 days)
Population: Participants in the Safety Population who experienced any AE were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AV-1 30 mg | Number of Participants by Severity of AEs | Moderate | 2 Participants |
| AV-1 30 mg | Number of Participants by Severity of AEs | Mild | 1 Participants |
| AV-1 30 mg | Number of Participants by Severity of AEs | Severe | 0 Participants |
| AV-1 90 mg | Number of Participants by Severity of AEs | Moderate | 0 Participants |
| AV-1 90 mg | Number of Participants by Severity of AEs | Mild | 3 Participants |
| AV-1 90 mg | Number of Participants by Severity of AEs | Severe | 0 Participants |
| AV-1 250 mg | Number of Participants by Severity of AEs | Moderate | 0 Participants |
| AV-1 250 mg | Number of Participants by Severity of AEs | Mild | 0 Participants |
| AV-1 250 mg | Number of Participants by Severity of AEs | Severe | 0 Participants |
| AV-1 500 mg | Number of Participants by Severity of AEs | Moderate | 0 Participants |
| AV-1 500 mg | Number of Participants by Severity of AEs | Mild | 1 Participants |
| AV-1 500 mg | Number of Participants by Severity of AEs | Severe | 0 Participants |
| AV-1 1000 mg | Number of Participants by Severity of AEs | Moderate | 0 Participants |
| AV-1 1000 mg | Number of Participants by Severity of AEs | Mild | 3 Participants |
| AV-1 1000 mg | Number of Participants by Severity of AEs | Severe | 1 Participants |
| Placebo | Number of Participants by Severity of AEs | Mild | 3 Participants |
| Placebo | Number of Participants by Severity of AEs | Severe | 0 Participants |
| Placebo | Number of Participants by Severity of AEs | Moderate | 0 Participants |
Primary
Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs
Number of participants with abnormal 12-lead ECG reported as a TEAE of electrocardiogram QT prolonged by the investigator. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related.
Time frame: Baseline up to Day 120 (± 5 days)
Population: Participants in the Safety Population were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV-1 30 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 2 Participants |
| AV-1 90 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 250 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 500 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 1000 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 1 Participants |
| Placebo | Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Reported as TEAEs | 0 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Clinical laboratory abnormalities reported as TEAEs by the investigator. Clinical laboratory abnormalities were defined as any abnormal findings in analysis of hematology, serum chemistry, coagulation, and urine parameters. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related.
Time frame: Baseline up to Day 120 (± 5 days)
Population: The Safety population included all participants who received any amount of the investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AV-1 30 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hematology (blood glucose increased) | 0 Participants |
| AV-1 30 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Serum chemistry | 0 Participants |
| AV-1 30 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Coagulation | 0 Participants |
| AV-1 30 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| AV-1 90 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Coagulation | 0 Participants |
| AV-1 90 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Serum chemistry | 0 Participants |
| AV-1 90 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hematology (blood glucose increased) | 0 Participants |
| AV-1 90 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| AV-1 250 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| AV-1 250 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Coagulation | 0 Participants |
| AV-1 250 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Serum chemistry | 0 Participants |
| AV-1 250 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hematology (blood glucose increased) | 0 Participants |
| AV-1 500 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hematology (blood glucose increased) | 0 Participants |
| AV-1 500 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| AV-1 500 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Serum chemistry | 0 Participants |
| AV-1 500 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Coagulation | 0 Participants |
| AV-1 1000 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Coagulation | 0 Participants |
| AV-1 1000 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| AV-1 1000 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Serum chemistry | 0 Participants |
| AV-1 1000 mg | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hematology (blood glucose increased) | 1 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Serum chemistry | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Coagulation | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Hematology (blood glucose increased) | 0 Participants |
Primary
Number of Participants With Physical Examination Abnormalities Reported as TEAEs
A full physical examination included examination of skin; head, ears, eyes, nose, throat (HEENT); neck; thyroid; lungs; heart; cardiovascular; abdomen; lymph nodes; and musculoskeletal system/extremities. Focused examination included lungs, cardiovascular, abdomen, and skin. Investigator could perform targeted, symptom-directed physical examination. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related.
Time frame: Baseline up to Day 120 (± 5 days)
Population: Participants in the Safety Population were evaluated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Heart | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Musculoskeletal system/extremities | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Thyroid | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Skin (dermatitis contact) | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Neck | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lymph nodes | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Cardiovascular | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Abdomen | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lungs | 0 Participants |
| AV-1 30 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | HEENT | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Cardiovascular | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Abdomen | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Musculoskeletal system/extremities | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Heart | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | HEENT | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lungs | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lymph nodes | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Neck | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Skin (dermatitis contact) | 0 Participants |
| AV-1 90 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Thyroid | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Heart | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Neck | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Abdomen | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | HEENT | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Musculoskeletal system/extremities | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Cardiovascular | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lungs | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Skin (dermatitis contact) | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Thyroid | 0 Participants |
| AV-1 250 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lymph nodes | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lymph nodes | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Neck | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Cardiovascular | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Thyroid | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Skin (dermatitis contact) | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Abdomen | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lungs | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | HEENT | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Heart | 0 Participants |
| AV-1 500 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Musculoskeletal system/extremities | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lymph nodes | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Heart | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | HEENT | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lungs | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Abdomen | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Neck | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Thyroid | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Skin (dermatitis contact) | 1 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Musculoskeletal system/extremities | 0 Participants |
| AV-1 1000 mg | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Cardiovascular | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lungs | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Thyroid | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Cardiovascular | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Musculoskeletal system/extremities | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | HEENT | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Lymph nodes | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Heart | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Neck | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Abdomen | 0 Participants |
| Placebo | Number of Participants With Physical Examination Abnormalities Reported as TEAEs | Skin (dermatitis contact) | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
An AE or suspected adverse reaction was considered an SAE if, in the view of either the Investigator or Sponsor, it resulted in any of the following outcome: * Death * A life-threatening AE * Inpatient hospitalization or prolongation of existing hospitalization * a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * A congenital anomaly/birth defect Important medical events that did not result in death, was life-threatening, or required hospitalizations could have been considered serious when, based upon appropriate medical judgment, they jeopardized the participant and required medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: Baseline up to Day 120 (± 5 days)
Population: Participants in the Safety Population were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV-1 30 mg | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| AV-1 90 mg | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| AV-1 250 mg | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| AV-1 500 mg | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| AV-1 1000 mg | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
Primary
Number of Participants With TEAEs
An adverse event (AE) was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure.
Time frame: Baseline up to Day 120 (± 5 days)
Population: Participants in the Safety Population were evaluated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV-1 30 mg | Number of Participants With TEAEs | 3 Participants |
| AV-1 90 mg | Number of Participants With TEAEs | 3 Participants |
| AV-1 250 mg | Number of Participants With TEAEs | 0 Participants |
| AV-1 500 mg | Number of Participants With TEAEs | 1 Participants |
| AV-1 1000 mg | Number of Participants With TEAEs | 4 Participants |
| Placebo | Number of Participants With TEAEs | 3 Participants |
Primary
Number of Participants With Vital Sign Abnormalities Reported as TEAEs
Vital sign measurements included systolic and diastolic blood pressure, oral body temperature, heart rate, and respiratory rate. A TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure whether or not considered drug related.
Time frame: Baseline up to Day 120 (± 5 days)
Population: Participants in the Safety Population were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AV-1 30 mg | Number of Participants With Vital Sign Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 90 mg | Number of Participants With Vital Sign Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 250 mg | Number of Participants With Vital Sign Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 500 mg | Number of Participants With Vital Sign Abnormalities Reported as TEAEs | 0 Participants |
| AV-1 1000 mg | Number of Participants With Vital Sign Abnormalities Reported as TEAEs | 0 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities Reported as TEAEs | 0 Participants |
Secondary
Apparent Terminal Half-life (t1/2) of AV-1
t1/2 is defined as terminal half-life, calculated as: ln(2)/ λz, where λz is apparent terminal elimination rate constant.
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | Apparent Terminal Half-life (t1/2) of AV-1 | 910 hours | Geometric Coefficient of Variation 15.8 |
| AV-1 90 mg | Apparent Terminal Half-life (t1/2) of AV-1 | 631 hours | Geometric Coefficient of Variation 25 |
| AV-1 250 mg | Apparent Terminal Half-life (t1/2) of AV-1 | 768 hours | Geometric Coefficient of Variation 33.8 |
| AV-1 500 mg | Apparent Terminal Half-life (t1/2) of AV-1 | 700 hours | Geometric Coefficient of Variation 24.4 |
| AV-1 1000 mg | Apparent Terminal Half-life (t1/2) of AV-1 | 732 hours | Geometric Coefficient of Variation 19.5 |
Secondary
Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1
AUC0-infinity was calculated as: AUC from time 0 to the last quantifiable concentration (AUC0-tlast) + (last observed serum drug concentration \[Ct\] / Apparent terminal elimination rate constant \[λz\]).
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: The pharmacokinetic (PK) population included participants who received the full dose of AV-1 and had at minimum all samples from predose through 1.5 hours from the start of infusion and had sufficient concentration data to support accurate estimation of at least 1 PK parameter. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1 | 7940 μg*hour/mL | Geometric Coefficient of Variation 14.9 |
| AV-1 90 mg | Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1 | 16700 μg*hour/mL | Geometric Coefficient of Variation 29.7 |
| AV-1 250 mg | Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1 | 52800 μg*hour/mL | Geometric Coefficient of Variation 33.7 |
| AV-1 500 mg | Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1 | 136000 μg*hour/mL | Geometric Coefficient of Variation 48.1 |
| AV-1 1000 mg | Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-infinity) of AV-1 | 250000 μg*hour/mL | Geometric Coefficient of Variation 15.8 |
Secondary
AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1
AUC0-48 was calculated using the linear trapezoidal rule method.
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1 | 443 μg*hour/mL | Geometric Coefficient of Variation 16.1 |
| AV-1 90 mg | AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1 | 1340 μg*hour/mL | Geometric Coefficient of Variation 19.7 |
| AV-1 250 mg | AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1 | 3380 μg*hour/mL | Geometric Coefficient of Variation 20.7 |
| AV-1 500 mg | AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1 | 11400 μg*hour/mL | Geometric Coefficient of Variation 74.1 |
| AV-1 1000 mg | AUC From Time 0 to 48 Hours Postdose (AUC0-48) of AV-1 | 16000 μg*hour/mL | Geometric Coefficient of Variation 20.2 |
Secondary
AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
AUC0-tlast was calculated using the linear trapezoidal method.
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | 7140 μg*hour/mL | Geometric Coefficient of Variation 12.4 |
| AV-1 90 mg | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | 15900 μg*hour/mL | Geometric Coefficient of Variation 27.9 |
| AV-1 250 mg | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | 48300 μg*hour/mL | Geometric Coefficient of Variation 30.6 |
| AV-1 500 mg | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | 129000 μg*hour/mL | Geometric Coefficient of Variation 48 |
| AV-1 1000 mg | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | 233000 μg*hour/mL | Geometric Coefficient of Variation 16.7 |
Secondary
Maximum Observed Serum Concentration (Cmax) of AV-1
Cmax is defined as maximum observed serum drug concentration.
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | Maximum Observed Serum Concentration (Cmax) of AV-1 | 12.7 μg/mL | Geometric Coefficient of Variation 10.8 |
| AV-1 90 mg | Maximum Observed Serum Concentration (Cmax) of AV-1 | 41.8 μg/mL | Geometric Coefficient of Variation 13.6 |
| AV-1 250 mg | Maximum Observed Serum Concentration (Cmax) of AV-1 | 98.0 μg/mL | Geometric Coefficient of Variation 22 |
| AV-1 500 mg | Maximum Observed Serum Concentration (Cmax) of AV-1 | 332 μg/mL | Geometric Coefficient of Variation 72 |
| AV-1 1000 mg | Maximum Observed Serum Concentration (Cmax) of AV-1 | 654 μg/mL | Geometric Coefficient of Variation 87.2 |
Secondary
Number of Participants With Detectable Anti-AV-1 Antibody
Serum samples for measurement of anti-AV-1 antibody levels were analyzed by a validated electrochemiluminescence enzyme-linked immunosorbent assay method used for detection and confirmation of pre-existing and treatment-emergent anti-AV-1 antibodies in serum samples based on the MesoScale Discovery platform that utilized labeled AV-1 for detection of anti-AV-1 antibodies and treatment-emergent antibodies. Number of participants with detectable anti-AV-1 antibody
Time frame: Baseline, Days 29 (±2), 85 (±5), and 120 (±5)
Population: Participants in the Safety Population were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AV-1 30 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 120 (±5) | 0 Participants |
| AV-1 30 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Baseline | 0 Participants |
| AV-1 30 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 29 (±2) | 0 Participants |
| AV-1 30 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 85 (±5) | 0 Participants |
| AV-1 90 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 29 (±2) | 0 Participants |
| AV-1 90 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Baseline | 0 Participants |
| AV-1 90 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 85 (±5) | 0 Participants |
| AV-1 90 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 120 (±5) | 0 Participants |
| AV-1 250 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Baseline | 1 Participants |
| AV-1 250 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 29 (±2) | 0 Participants |
| AV-1 250 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 85 (±5) | 0 Participants |
| AV-1 250 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 120 (±5) | 1 Participants |
| AV-1 500 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 120 (±5) | 0 Participants |
| AV-1 500 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Baseline | 0 Participants |
| AV-1 500 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 29 (±2) | 0 Participants |
| AV-1 500 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 85 (±5) | 0 Participants |
| AV-1 1000 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Baseline | 0 Participants |
| AV-1 1000 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 120 (±5) | 0 Participants |
| AV-1 1000 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 85 (±5) | 0 Participants |
| AV-1 1000 mg | Number of Participants With Detectable Anti-AV-1 Antibody | Day 29 (±2) | 0 Participants |
| Placebo | Number of Participants With Detectable Anti-AV-1 Antibody | Day 120 (±5) | 0 Participants |
| Placebo | Number of Participants With Detectable Anti-AV-1 Antibody | Baseline | 0 Participants |
| Placebo | Number of Participants With Detectable Anti-AV-1 Antibody | Day 29 (±2) | 0 Participants |
| Placebo | Number of Participants With Detectable Anti-AV-1 Antibody | Day 85 (±5) | 0 Participants |
Secondary
Time to Reach Cmax (Tmax) of AV-1
Tmax is defined as Time to reach maximum serum concentration following drug administration.
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AV-1 30 mg | Time to Reach Cmax (Tmax) of AV-1 | 2.00 hours |
| AV-1 90 mg | Time to Reach Cmax (Tmax) of AV-1 | 4.00 hours |
| AV-1 250 mg | Time to Reach Cmax (Tmax) of AV-1 | 1.38 hours |
| AV-1 500 mg | Time to Reach Cmax (Tmax) of AV-1 | 2.49 hours |
| AV-1 1000 mg | Time to Reach Cmax (Tmax) of AV-1 | 2.00 hours |
Secondary
Total Serum Clearance (CL) of AV-1
Total serum clearance was calculated as dose divided by AUC0-infinity.
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | Total Serum Clearance (CL) of AV-1 | 0.00378 Liter/hour | Geometric Coefficient of Variation 14.9 |
| AV-1 90 mg | Total Serum Clearance (CL) of AV-1 | 0.00539 Liter/hour | Geometric Coefficient of Variation 29.7 |
| AV-1 250 mg | Total Serum Clearance (CL) of AV-1 | 0.00474 Liter/hour | Geometric Coefficient of Variation 33.7 |
| AV-1 500 mg | Total Serum Clearance (CL) of AV-1 | 0.00366 Liter/hour | Geometric Coefficient of Variation 48.1 |
| AV-1 1000 mg | Total Serum Clearance (CL) of AV-1 | 0.00399 Liter/hour | Geometric Coefficient of Variation 15.8 |
Secondary
Volume of Distribution During the Terminal Phase (Vz) of AV-1
Volume of distribution during the terminal phase was calculated as dose divided by (AUC0-infinity\*λz).
Time frame: Predose (within 15 minutes); at 0.5, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the start of infusion; Days 5, 8, 15, 22, 29, 43, 57, 85, and 120
Population: Participants in the PK Population who have were analyzed. As placebo group did not receive AV-1, PK analysis for placebo group is not applicable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AV-1 30 mg | Volume of Distribution During the Terminal Phase (Vz) of AV-1 | 4.96 Liter | Geometric Coefficient of Variation 9 |
| AV-1 90 mg | Volume of Distribution During the Terminal Phase (Vz) of AV-1 | 4.90 Liter | Geometric Coefficient of Variation 21.7 |
| AV-1 250 mg | Volume of Distribution During the Terminal Phase (Vz) of AV-1 | 5.25 Liter | Geometric Coefficient of Variation 24 |
| AV-1 500 mg | Volume of Distribution During the Terminal Phase (Vz) of AV-1 | 3.70 Liter | Geometric Coefficient of Variation 53.6 |
| AV-1 1000 mg | Volume of Distribution During the Terminal Phase (Vz) of AV-1 | 4.22 Liter | Geometric Coefficient of Variation 25 |