Healthy Volunteer Safety StudyPhase 1NCT01166984
AB103 Peptide Antagonist in Healthy Volunteers
A Phase 1 study testing AB103 in people with Healthy Volunteer Safety Study, run by Atox Bio Ltd at 1 site in United States.
Trial summary
The primary objective of this study is to establish the safety profile and maximum tolerated dose (MTD) of AB103 given as a single intravenous (IV) infusion in healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer Safety Study
- What is being tested?
- AB103
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Jun 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland School of Medicine
Baltimore, Maryland, 21201
About this study
Official title: Phase 1, Double Blind, Placebo-Controlled, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Clinical Trial of AB103, A Peptide Antagonist in Healthy Volunteers
The primary objective of this study is to establish the safety profile and maximum tolerated dose (MTD) of AB103 given as a single intravenous (IV) infusion in healthy volunteers.
Read the 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.
- Conditions
- Healthy Volunteer Safety Study
- Being tested
- AB103, Placebo
- Keywords
- sepsis, septic shock
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AB103Drug
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
PlaceboDrug
Single intravenous infusion of normal saline (0.9% sodium chloride) administered over approximately 10 minutes
| Study group | Role | What they receive |
|---|---|---|
| AB103 7.5 µg/kg | Experimental | AB103 7.5 µg/kg administered as a single IV infusion Receives: Drug: AB103 |
| AB103 37.5 µg/kg | Experimental | AB103 37.5 µg/kg administered as a single IV infusion Receives: Drug: AB103 |
| AB103 150 µg/kg | Experimental | AB103 150 µg/kg administered as a single IV infusion Receives: Drug: AB103 |
| AB103 450 µg/kg | Experimental | AB103 450 µg/kg administered as a single IV infusion Receives: Drug: AB103 |
| Placebo | Placebo comparator | Normal saline (0.9% sodium chloride) administered as a single IV infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number Adverse Events (AEs)
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.
Measured: 2 weeks
Number of Serious Adverse Events (SAEs)
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:
- Results in death
- Is life-threatening (i.e., the subject was, in the opinion of the Investigator, at immediate risk of death from the event as it occurred)
- Requires or prolongs hospitalization
- Results in persistent or significant disability or incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions)
- Is a congenital anomaly or birth defect, or
- Is an important and significant medical event.
Measured: 2 weeks
Number of Dose-limiting Toxicities (DLTs)
DLTs were defined as the emergence of one or more selected AEs that reached a threshold that may justify stopping the trial.
Measured: 2 weeks
Secondary outcomes (4)
Area Under the Plasma Concentration-time Curve (AUC)
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.
Measured: 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
Maximum plasma concentration
Measured: 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)
Apparent terminal plasma half-life (T1/2) is the amount of time for plasma concentrations to decline by 50%.
Measured: 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)
Clearance (CL) is the volume of plasma completely cleared of drug per unit of time.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2010 (estimated)
- Study startSep 2010
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy Volunteer Safety StudyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atox Bio Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan Cross, MD, Principal investigator, University of Maryland, College Park
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01166984
- Sponsor's protocol ID
- ATB-001
- Status last verified
- Mar 2021
- First submitted
- 20 Jul 2010
- Last updated
- 9 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Double Blind, Placebo-Controlled, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Clinical Trial of AB103, A Peptide Antagonist in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01166984
- Acronym / sponsor ID
- ATB-001
- Conditions
- Healthy Volunteer Safety Study
- Keywords
- sepsis, septic shock
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Atox Bio LtdIndustry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 21 Jul 2010 (estimated)
- Results
- Posted 27 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to establish the safety profile and maximum tolerated dose (MTD) of AB103 given as a single intravenous (IV) infusion in healthy volunteers.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| AB103 7.5 µg/kg | Experimental | Drug: AB103AB103 7.5 µg/kg administered as a single IV infusion |
| AB103 37.5 µg/kg | Experimental | Drug: AB103AB103 37.5 µg/kg administered as a single IV infusion |
| AB103 150 µg/kg | Experimental | Drug: AB103AB103 150 µg/kg administered as a single IV infusion |
| AB103 450 µg/kg | Experimental | Drug: AB103AB103 450 µg/kg administered as a single IV infusion |
| Placebo | Placebo comparator | Drug: PlaceboNormal saline (0.9% sodium chloride) administered as a single IV infusion |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AB103Single 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 | Drug | AB103 150 µg/kg, AB103 37.5 µg/kg, AB103 450 µg/kg, AB103 7.5 µg/kg |
| PlaceboSingle intravenous infusion of normal saline (0.9% sodium chloride) administered over approximately 10 minutes | Drug | Placebo |
Primary outcome
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.
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: * Results in death * Is life-threatening (i.e., the subject was, in the opinion of the Investigator, at immediate risk of death from the event as it occurred) * Requires or prolongs hospitalization * Results in persistent or significant disability or incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions) * Is a congenital anomaly or birth defect, or * Is an important and significant medical event.
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.
4 secondary outcomes
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan Cross, MD principal investigator
University of Maryland, College Park
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AB103 in people with Healthy Volunteer Safety Study, run by Atox Bio Ltd at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number Adverse Events (AEs) (time frame: 2 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2021.