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Purpose

The goal of this clinical trial is to determine the prophylactic and therapeutic effect of AV-1 in healthy adults using a DENV-3 controlled human infection model (CHIM)

Condition

Eligibility

Eligible Ages
Between 18 Years and 55 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Males or nonpregnant, nonlactating females who were assigned males and females at birth, of any race, between 18 and 55 years of age - Body mass index between 18.5 and 34.9 kg/m², inclusive, at Screening - 12-lead electrocardiogram (ECG) and clinical laboratory evaluations within normal range at screening. Normal ECG is defined as the absence of: 1. QTcF >450 ms in men or >460 ms in women 2. PR >220 ms ventricular or atrial premature contractions in couplets or higher in grouping 3. Complete left or right bundle branch block 4. 2nd or 3rd degree atrioventricular block 5. Sustained ventricular or atrial arrhythmia 6. ST elevation consistent with cardiac ischemia - Subjects in good health as determined by past medical history, medication use, physical examination, vital signs, and 12-lead ECG at Screening - Females of childbearing potential must agree to use effective contraception through study duration 1. Reliable methods of contraception include: long acting, reversible contraception (LARC), hormonal birth control* (implantable device, hormonal patch, hormonal vaginal ring, oral contraception, Depo-Provera injection, etc.), surgical sterilization (hysterectomy, tubal ligation, or tubal coil at least 90 days prior to Investigational Product [IP] dosing) 2. Must agree to not donate ova or oocytes during the study 3. Postmenopausal women must have had ≥12 months of spontaneous amenorrhea without an alternative medical cause for amenorrhea, with follicle-stimulating hormone (FSH) concentration ≥40 mIU/mL at Screening and must have a negative pregnancy test result at Screening and Day-1 or Day 0 4. Surgically sterile women (defined as those who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, tubal ligation, or an Essure placement with radiological confirmation test at least 90 days after procedure) must have a negative pregnancy test result at Screening and Study Day -1 (Cohort A) or Study Day 0 (Cohort B). *Subjects on hormonal birth control must not be on medications or other agents that decrease the effectiveness of hormonal birth control - Male subjects having sexual intercourse with biologic females and who are biologically capable of fathering children must agree and commit to use male condoms from Study Day -1 until the follow-up visit on Study Day 155 (± 7). A male subject is considered capable of fathering children even if his sexual partner is sterile or using contraceptives a. Male subjects must refrain from sperm donation from Study Day -1 until the follow-up visit on Study Day 155 (± 7) - Understands study and agrees to and is available for all procedures throughout the study - Agree to follow study restrictions and are able to sign an informed consent form

Exclusion Criteria

  • Any significant medical condition who, in the opinion of the investigator, would interfere with the ability to participate in the study or increase the risk of participating for that subject based on the Investigator's Brochures and the safety profiles of AV-1 and rDEN3Δ30 - Any psychiatric condition or history of psychiatric 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 the participation for that subject - History of significant alcoholism or drug/chemical abuse within 12 months prior to Study Day -1 that has caused medical, occupational, or family problems as indicated by subject history - Currently being treated for peptic ulcer disease or Helicobacter pylori or has been treated within the 6 months prior to Day -1 - Confirmed screening laboratory value of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), or serum creatinine. Values of Grade 1 or above for these tests may be repeated once to confirm a Grade 1 or above value - History of or suspected coagulopathy - Alcohol consumption of >21 units* per week for males and >14 units per week for females (*1 unit of alcohol equals 12 oz [360 mL] beer, 1.5 oz [45 mL] liquor, or 5 oz [150 mL] wine) through Study Day 28 - Positive urine drug screen at Screening or Day -1 for drugs of abuse defined as Amphetamines, Barbiturates, Benzodiazepines, Cocaine Metabolite, Opiates, Oxycodone, Phencyclidine without confirmation of medical need verified by prescription (ie, anxiolytics or pain medications). - Women with positive pregnancy test at either Screening visit, Study Day -1, or Study Day 0 - Seropositive for Hepatitis B surface antigen (HBsAg) or positive for Hepatitis C RNA at Screening - Any confirmed or suspected immunosuppressive or immunodeficient condition, including, but not limited to, human immunodeficiency virus infection, or use of anti-cancer chemotherapy or radiation therapy (cytotoxic) in the 3 years prior to Screening - Plan to travel to an area with active Zika virus (ZIKV) or DENV, transmission during the study or returned from travel to an area with active transmission within 30 days of Screening. (*Refer to the Centers for Disease Control and Prevention [CDC] website for areas with active ZIKV or DENV) - History of vaccination with a licensed or investigational ZIKV vaccine, DENV vaccine*, yellow fever virus (YFV) vaccine, or Japanese encephalitis vaccine or reportedly diagnosed with a ZIKV or DENV infection or disease. (*Includes subject's verbal history of vaccination or disease). - Positive serology to DENV, ZIKV, West Nile virus (WNV), YFV, or St. Louis encephalitis virus (SLE) within 60 days of Screening - History of anaphylaxis to any drug compound, (including citrate or polysorbate), food, or other substance, unless approved by the investigator - Major surgery within the last 3 months - Previously treated with a licensed or investigational monoclonal or polyclonal antibody within the past 18 months prior to Study Day -1 - Received any investigational drug product within that last 28 days of Study Day -1 - Any prohibited medication within the past 28 days or plans to use prohibited medication during the study. Prohibited medications include oral/systemic anti-neoplastic agents, medications/supplements known to alter drug absorption, metabolism, or elimination processes (eg, St. John's wort), immunosuppressive drugs - Use of any aspirin product in the 7 days prior to Study Day -1 through 14 days post-challenge - Use of an NSAID from 48 hours prior to challenge through 14 days post-challenge - Participants who have received or plan to receive any vaccination (live), experimental or otherwise, within the past 28 days or after Study Day -1 and 14 days (2 weeks) for inactivated vaccines and mRNA vaccines - Has received blood products within 60 days (2 months) prior to Study Day -1 (Cohort A) or Day 0 (Cohort B) - Has donated or lost in excess of 450 mL of blood or plasma within 56 days (8 weeks) of Study Day -1. The subject must also agree to refrain from donating blood or plasma during the study - Has poor peripheral venous access during screening - Has previously completed or was withdrawn from this study - Is a current study site staff paid entirely or partially by the contract for this study, or staff who are supervised by the principal or sub-investigators - Subjects, who in the opinion of the investigator, should not participate in this study

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group 1A prophylaxis
  • Drug: AV-1 100 mg
    human monoclonal antibody (mAb) intravenous solution or
  • Drug: Placebo
    (0.9% saline intravenous solution) 12:2
Experimental
Group 2A prophylaxis
  • Drug: AV-1 300 mg
    human monoclonal antibody (mAb) intravenous solution or
  • Drug: Placebo
    (0.9% saline intravenous solution) 12:2
Experimental
Group 3A prophylaxis
  • Drug: AV-1 900 mg
    human monoclonal antibody (mAb) intravenous solution or
  • Drug: Placebo
    (0.9% saline intravenous solution) 12:2
Experimental
Group 1B treatment
  • Drug: AV-1 100 mg
    human monoclonal antibody (mAb) intravenous solution or
  • Drug: Placebo
    (0.9% saline intravenous solution) 12:2
Experimental
Group 2B treatment
  • Drug: AV-1 300 mg
    human monoclonal antibody (mAb) intravenous solution or
  • Drug: Placebo
    (0.9% saline intravenous solution) 12:2
Experimental
Group 3B treatment
  • Drug: AV-1 900 mg
    human monoclonal antibody (mAb) intravenous solution or
  • Drug: Placebo
    (0.9% saline intravenous solution) 12:2

Recruiting Locations

Center for Immunization Research (CIR) JHBSPH
Baltimore, Maryland 21205
Contact:
Farah Jeong
443-604-7954
fjeong1@jh.edu

Center for Immunization Research Inpatient Unit
Baltimore, Maryland 21224
Contact:
Farah Jeong
443-604-7954
fjeong1@jh.edu

UVM Larner College of Medicine Department of MMG
Burlington, Vermont 05405
Contact:
Patricia Lutton
802-656-0013
uvmvtc@uvm.edu

More Details

Status
Recruiting
Sponsor
AbViro LLC

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.