A Randomized, Double-Blind, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Intramuscular Doses of ETI-204 in Adult Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Inhalational Anthrax
- Sponsor
- Elusys Therapeutics
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Number of Participants Who Experienced Adverse Events
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This study is to evaluate the safety, local tolerability, pharmacokinetics (PK) and immunogenicity of escalating single intramuscular (IM) doses of ETI-204 in healthy volunteers
Detailed Description
Following completion of a Screening visit subjects will arrive at the clinic on Day -1. On Day 1, subjects will be randomized in a 3:1 ratio to receive an IM dose of either ETI-204 or matching placebo, respectively: Cohort 1: 4 subjects randomized to 4 mg/kg ETI-204 or matching placebo Cohort 2: 8 subjects randomized to 8 mg/kg ETI-204 or matching placebo Cohort 3: 8 subjects randomized to 16 mg/kg ETI-204 or matching placebo Cohort 4: 8 subjects randomized to 20 mg/kg ETI-204 or matching placebo Cohort 5: 8 subjects randomized to 24 mg/kg ETI-204 or matching placebo Study drug will be injected bilaterally into the vastus lateralis muscles, with the subject in a supine position. A separate syringe with a 21-gauge,1.5-inch needle will be used for each injection. The number of injections and injection volume will increase with increasing dose allowing for an assessment of increasing IM ETI-204 doses and the tolerability of a larger number of injections and larger injection volume. Subjects will be pretreated with 50 mg oral diphenhydramine approximately 30 minutes prior to administration of study drug. Subjects will be discharged from the study facility on Day 4 following completion of study assessments and will return to the study facility for additional visits on Days 7, 10, 15 (±3 days), 29 (±3 days), 43 (±3 days), and 71 (±4 days). Decisions to dose-escalate will be made by the investigator(s) in conjunction with the sponsor and will be based solely on the available safety and local tolerability data up to and including Day 4.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Females or males ≥18 years of age;
- •All females regardless of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test at Screening and Day -1;
- •Females of childbearing potential (i.e., not postmenopausal or surgically sterile) must agree to practice abstinence or to use a medically accepted method of contraception from the time of Screening through 30 days after the final study visit. Acceptable methods of contraception include diaphragm/cervical cap with spermicide; sponge with spermicide; condom with spermicide; or intrauterine device with condom or spermicide. The following contraceptive methods are acceptable only when used with a condom and spermicide: birth control pills, birth control patches, vaginal ring, hormone under the skin, or hormone injections;
- •Postmenopausal females, defined as females who have had amenorrhea for at least 12 months either naturally or following cessation of all exogenous hormonal treatments, and have a follicle stimulating hormone level of \>40 mIU/mL at Screening;
- •Females who have undergone surgical sterilization, including hysterectomy, bilateral oophorectomy, bilateral salpingectomy, tubal ligation, or tubal essure;
- •Males must agree to practice abstinence or use a condom with spermicide and to refrain from sperm donation from Screening during the study and for 30 days after the final study visit;
- •Provide written informed consent;
- •Willing to comply with study restrictions.
Exclusion Criteria
- •Body weight \>100 kg;
- •Body mass index ≥32 kg/m2;
- •Pregnant or lactating female;
- •Clinically significant comorbidity that would interfere with completion of the study procedures or objectives, or compromise the subject's safety;
- •Supine systolic blood pressure (BP) ≥150 mmHg or ≤90 mmHg or diastolic BP ≥95 mmHg;
- •Use of H1 receptor antagonists (i.e., antihistamines) within 5 days prior to Day 1;
- •Evidence of drug or alcohol abuse within 6 months of Day 1 as determined by the Investigator;
- •Positive test result for drugs of abuse (with the exception of medically prescribed drugs) at Screening or on Day -1;
- •Positive test for alcohol at Screening, subject to Investigator's discretion. Subjects who test positive for alcohol at Day -1 are excluded from the study;
- •Treatment with an investigational agent within 30 days or 5 half-lives of the investigational agent at Day 1 (whichever is longer);
Outcomes
Primary Outcomes
Number of Participants Who Experienced Adverse Events
Time Frame: Up to 71 (+/- 4) days or for 30 additional days after the final study visit for subjects with ongoing adverse events at the final scheduled study visit, for each group.
Safety was assessed for all subjects in the Safety Population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical examinations, injection site assessments, skin assessments for presence/absence of rash, and adverse events (AEs).
Secondary Outcomes
- Maximum Observed Plasma Concentration of ETI-204 (Cmax)(Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.)
- Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)(Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.)
- Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last)(Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.)
- Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf)(Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.)
- Half-life (t1/2)(Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.)
- Apparent Clearance (CL/F)(Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.)
- Number of Participants With Anti-ETI-204 Antibodies(Pre-dose and on Days 10, 43, and 71 after the IM injection of ETI-204 or placebo on Day 1.)