- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01166984
AB103 Peptide Antagonist in Healthy Volunteers
Phase 1, Double Blind, Placebo-Controlled, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Clinical Trial of AB103, A Peptide Antagonist in Healthy Volunteers
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
After consent and establishing eligibility for the study, each subject received a single IV infusion of escalating doses of AB103 (7.5, 37.5, 150, 450 μg/kg in 5 subjects at each dose) or placebo (n=5). Screening blood chemistry, hematology, coagulation, urinalysis, vital signs, and electrocardiogram (ECG) were used to assure medical fitness to participate in the study. These measures were repeated during and after treatment with AB103 to monitor for adverse events (AEs). ECG and pulse oximetry was monitored continuously starting 15 minutes before the infusion and for 2 hours after each infusion. Vital signs (sitting blood pressure, temperature, heart rate, respiratory rate, and pulse oximetry) and ECG measurements were recorded every 15 minutes for the first two hours starting from the beginning of the infusion and then approximately 24 hours later. Blood chemistry, hematology, coagulation, and urinalysis, were repeated one day and one week after infusions. AEs either observed by the investigator or reported spontaneously by the subjects were recorded at each study visit. Subjects kept a 7-day diary starting on the day of infusion to record any AEs. The primary basis on which escalation was based was dose limiting toxicities (DLTs) defined as the emergence of one or more selected AEs that reached a threshold which justified stopping the trial. After safety monitoring committee review of safety data, progression to the next cohort was to occur as follows:
- If none of the 5 AB103 subjects in a cohort experienced a non-extreme DLT, escalation to the next dose cohort was to occur.
- If 1 of 5 subjects receiving AB103 in a cohort experienced a non-extreme DLT, then a total of 8 subjects (6 active: 2 placebo) were to be enrolled in that cohort before escalating to the next dose (escalation will only occur if no additional subjects (2 total) have a non-extreme DLT).
- If there were 0/6 or 1/6 active subjects with a non-extreme DLT at the highest dose, the highest dose was to be considered the MTD. If there were 2/6 active subjects with a non-extreme DLT in a cohort, then the next lowest dose was to be considered the MTD.
- If an extreme DLT occurred, the study was to be halted immediately.
Subjects in Cohorts #1 to #3 had a blood sample (40 milliliters, mL) drawn pre-infusion, 24 hours after the infusion (Day 2), and a final sample at the Day 6-8 clinic visit (total of 120 mL) for leukocyte phenotyping by flow cytometry. Subjects in Cohort #4 had a blood sample (40 mL) drawn pre-infusion, 1 hour after the infusion, and a final sample at the Day 6-8 clinic visit (total of 120 mL) for leukocyte phenotyping by flow cytometry.
For the pharmacokinetic (PK) analysis, blood was collected at the mid-point of the infusion and 1, 2, 5, 10, 20, 30, and 60 minutes and approximately 24 hours post-infusion, and plasma was isolated for quantitation of AB103 peptide concentrations.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201
- University of Maryland School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Be able to read, understand and sign the Informed Consent form and be willing to participate in all study procedures for the duration of the study.
- Be 18-to-40 years-of-age.
- Have adequate venous access.
- Have a body mass index between 20 and 29 kg/m2.
- Have a history and physical examination that demonstrate no clinically significant contraindication for participating in the study, in the judgment of the admitting physician and/or the site investigator.
- Have vital signs as follows: resting heart rate between 50 and 90 beats per minute (bpm), systolic blood pressure (BP) below 150 mm Hg and diastolic BP below 90 mm Hg.
- Have all blood chemistry, hematology, coagulation, and urinalysis analyte levels within 10% of normal laboratory limits.
- If female, not be pregnant or breast-feeding, nor plan to become pregnant for the duration of the study, have a negative pregnancy test.
- Agree to exercise adequate birth control from the time of the screening procedures to 14 days after the investigational agent administration (both males and females).
- Have an electrocardiogram (ECG) performed that demonstrates normal sinus rhythm, normal conductivity, and no clinically significant arrhythmias.
Exclusion Criteria:
- Be pregnant or lactating.
- Have autoimmune disease or asthma.
- Have been febrile within 3-days of the first infusion.
- Have a history of migraine headaches, as diagnosed by a physician.
- Have any acute or chronic medical illnesses or other condition that, in the opinion of the Investigator, might jeopardize the safety of the patient, or the adequate evaluation of study results.
- Be taking any medications to treat a chronic medical condition.
- Have participated in a research study where they received any experimental products within 30 days prior to study entry.
- Have ongoing drug abuse/dependence (including alcohol) by medical history.
- Have taken, within 14 days of planned dosing, any prescription or non-prescription medication (including ibuprofen, aspirin, of non-steroidal anti-inflammatory drugs) unless the Principal Investigator/Sub-Investigator, in consultation with the Medical Monitor, provides a statement justifying that the medication taken will not impact the results of this study (with rare exceptions taking prescription drugs will be grounds for exclusion).
- Have donated a unit of blood within the preceding 4-week period.
- Have allergy to either sulfa- or penicillin-based drugs.
- Have a history of vagal responses resulting in bradycardia.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AB103 7.5 µg/kg
AB103 7.5 µg/kg administered as a single IV infusion
|
Single intravenous infusion at doses of 7.5 µg/kg, 37.5 µg/kg, 150 µg/kg, or 450 µg/kg administered over approximately 10 minutes
|
Experimental: AB103 37.5 µg/kg
AB103 37.5 µg/kg administered as a single IV infusion
|
Single intravenous infusion at doses of 7.5 µg/kg, 37.5 µg/kg, 150 µg/kg, or 450 µg/kg administered over approximately 10 minutes
|
Experimental: AB103 150 µg/kg
AB103 150 µg/kg administered as a single IV infusion
|
Single intravenous infusion at doses of 7.5 µg/kg, 37.5 µg/kg, 150 µg/kg, or 450 µg/kg administered over approximately 10 minutes
|
Experimental: AB103 450 µg/kg
AB103 450 µg/kg administered as a single IV infusion
|
Single intravenous infusion at doses of 7.5 µg/kg, 37.5 µg/kg, 150 µg/kg, or 450 µg/kg administered over approximately 10 minutes
|
Placebo Comparator: Placebo
Normal saline (0.9% sodium chloride) administered as a single IV infusion
|
Single intravenous infusion of normal saline (0.9% sodium chloride) administered over approximately 10 minutes
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number Adverse Events (AEs)
Time Frame: 2 weeks
|
An AE is any untoward medical occurrence in a subject administered study drug and that does not necessarily have a causal relationship with the study drug.
An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug.
|
2 weeks
|
Number of Serious Adverse Events (SAEs)
Time Frame: 2 weeks
|
A serious adverse event (SAE) is an AE occurring during any study phase and at any dose of the study drug (AB103 or placebo) that fulfills one or more of the following criteria:
|
2 weeks
|
Number of Dose-limiting Toxicities (DLTs)
Time Frame: 2 weeks
|
DLTs were defined as the emergence of one or more selected AEs that reached a threshold that may justify stopping the trial.
|
2 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Plasma Concentration-time Curve (AUC)
Time Frame: Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Area under the plasma concentration-time curve (AUC) from time zero to infinity following a single dose of study drug, obtained via noncompartmental methods.
It is an integrated measure of study drug plasma exposure.
|
Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Cmax
Time Frame: Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Maximum plasma concentration
|
Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Apparent Terminal Plasma Half-life (T1/2)
Time Frame: Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Apparent terminal plasma half-life (T1/2) is the amount of time for plasma concentrations to decline by 50%.
|
Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Clearance (CL)
Time Frame: Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Clearance (CL) is the volume of plasma completely cleared of drug per unit of time.
|
Whole blood was collected pre-dose; at the mid-point of the infusion; at 1, 2, 5, 10, 20, 30, and 60 minutes post-infusion; and at approximately 24 hours post-infusion for the measurement of AB103 plasma concentrations.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alan Cross, MD, University of Maryland, College Park
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- ATB-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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