A Phase I, Double-Blind, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of NTM-1633 vs Placebo Administered Intravenously in Healthy Adults

National Institute of Allergy and Infectious Diseases (NIAID)1 site in 1 country24 target enrollmentSeptember 25, 2018

ConditionsBotulism

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Botulism
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Enrollment: 24
Locations: 1
Primary Endpoint: The occurrence of changes in heart rate in arm A
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase I, single-center, double-blind, placebo-controlled dose escalation trial of three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg). The purpose of this study is to evaluate the safety and tolerability of NTM-1633 in healthy adults. This is a first-in-human study consisting of three cohorts of eight subjects each. Dosing for each cohort is as follows: Two sentinel subjects will be administered a single 1-hour infusion (one NTM-1633, one placebo). No more than two subjects per day thereafter (at least 24 hrs will elapse between the dosing of each two subjects) will be dosed in the same manner until all subjects are dosed. Dose escalation will not occur until safety data through Day 8 is reviewed by the Safety Review Committee (SRC). Objective dose-escalation criteria and safety evaluations will be utilized. The study duration will be for approximately 8 months. Subjects in Cohort A will participate for approximately 17 weeks and Subjects in Cohorts B and C will participate approximately 21 weeks. Primary Objective: To assess the safety and tolerability of escalating doses of NTM-1633 administered intravenously in healthy adults.

Detailed Description

Registry

clinicaltrials.gov

Start Date

September 25, 2018

End Date

June 11, 2019

Last Updated

3 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Informed consent understood and signed.
•Healthy male or healthy, non-pregnant, non-lactating female.
•Willingness to comply and be available for all protocol procedures including inpatient confinement for 36 - 48 hours.
•Age between 18 and 45 years, inclusive on the day of infusion.
•Body Mass Index (BMI) of \> / =18.5 and \< 35 kg/m\^
•If the subject is female and of childbearing potential, she has a negative serum pregnancy test at screening and negative urine test within 24 hours prior to infusion.
•A woman is considered of childbearing potential unless post-menopausal (\> / = 1 year without menses) or surgically sterilized via bilateral oophorectomy, or hysterectomy or bilateral tubal ligation or successful Essure placement with documented confirmation test at least 3 months after the procedure.
•If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men or use acceptable contraception up to visit 12 of the study.
•Acceptable contraception methods are restricted to effective devices (Intrauterine Contraceptive Devices, NuvaRing(R)) or licensed hormonal products with use of method for a minimum of 28 days prior to dosing, condoms or diaphragm with spermicidal agents, monogamous relationship with a vasectomized partner
•The hemoglobin, platelet count, white blood cell count and absolute neutrophil count are within normal limits at the screening visit.

Exclusion Criteria

•History of a chronic medical condition that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject.
•Chronic medical conditions include diabetes; Asthma requiring use of medication in the year before screening; Autoimmune disorder such as lupus, Wegener's, rheumatoid arthritis, thyroid disease; Coronary artery disease; Chronic hypertension; History of malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine disease (except previous asthma which has required no treatment for the past year)
•History of severe allergic reaction of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobulins.
•Note: Severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema
•A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \> 450 milliseconds)
•Clinically significant abnormal electrocardiogram at screening.
•Clinically significant abnormal ECG results include: complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator
•Positive serology results for HIV, HBsAg, or HCV antibodies
•Febrile illness with temperature \> 37.6 degrees Celsius within 7 days of dosing
•Pregnant or breastfeeding