A Study to Determine the Safety of AV-1, an Antibody Being Developed for Treatment of Dengue, in Healthy Volunteers

NCT04273217 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: AV1-PPD-0005DMID 18-0016HHSN272201600028C
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Healthy volunteers; Monoclonal antibody; AV-1; Safety; Dengue

Outcome Measures

Primary Outcomes (7)

• 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.

  Baseline up to Day 120 (± 5 days)

• 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.

  Baseline up to Day 120 (± 5 days)

• 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.

  Baseline up to Day 120 (± 5 days)

• 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.

  Baseline up to Day 120 (± 5 days)

• 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.

  Baseline up to Day 120 (± 5 days)

• 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.

  Baseline up to Day 120 (± 5 days)

• 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.

  Baseline up to Day 120 (± 5 days)

Secondary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

Study Arms (6)

AV-1 30 mg

EXPERIMENTAL

Participants received a single intravenous (IV) infusion (infusion duration: 1 hour) of AV-1 30 mg on Day 1.

Drug: AV-1

AV-1 90 mg

EXPERIMENTAL

Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 90 mg on Day 1.

Drug: AV-1

AV-1 250 mg

EXPERIMENTAL

Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 250 mg on Day 1.

Drug: AV-1

AV-1 500 mg

EXPERIMENTAL

Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 500 mg on Day 1.

Drug: AV-1

AV-1 1000 mg

EXPERIMENTAL

Participants received a single IV infusion (infusion duration: 1 hour) of AV-1 1000 mg on Day 1.

Drug: AV-1

Placebo

PLACEBO COMPARATOR

Participants received a single IV infusion (infusion duration: 1 hour) of placebo matched to AV-1 on Day 1.

Drug: Placebo

Interventions

AV-1 DRUG

Single dose, administered by IV infusion (volume: 250 mL)

AV-1 1000 mg; AV-1 250 mg; AV-1 30 mg; AV-1 500 mg; AV-1 90 mg

Placebo DRUG

0.9% sterile saline. Administered by IV infusion (volume: 250 mL)

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must be in good health at Screening (reaffirmed at Check-in):

You may not qualify if:

• 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:
• 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.
• 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.
• Must be willing to not engage in sexual intercourse from Check-in until the final follow-up visit on Day 120 (± 5 days).
• 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).
• Any significant medical condition that, in the opinion of the Investigator or Sponsor, would interfere with the subject's ability to participate in the study or increase the risk of participating for that subject, based on the Investigator's Brochure and the safety profile of AV-1.
• Subject has one or more symptoms of a urinary tract infection (e.g. dysuria, frequent, urgency, or suprapubic pain) at Screening or Check-in.
• Has certain abnormal12-lead ECG (electrocardiogram) results according to the protocol, as assessed by the Investigator.
• Has abnormal laboratory values for certain hematology, serum chemistry, coagulation, or urinalysis tests according to the protocol, as assessed by the Investigator.

Sponsors & Collaborators

• AbViro LLC: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

PPD Austin Clinic, 7551 Metro Center Drive, Suite 200

Austin, Texas, 78744, United States

Location

Related Links

• FDA Medical Product Safety Information
• FDA Recalls, Market Withdrawals, and Safety Alerts

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Urban Ramstedt
• Organization: AbViro LLC

urban.ramstedt@abviro.com

617-818-8112

Study Officials

• Rebecca Wood-Horrall, MD

  PPD Development, LP

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2020
• First Posted: February 18, 2020
• Study Start: February 4, 2020
• Primary Completion: July 8, 2021
• Study Completion: July 8, 2021
• Last Updated: October 31, 2022
• Results First Posted: October 31, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)