Volunteers, Healthy
Conditions
Keywords
safety, pharmacokinetics
Brief summary
Study BTI-101 is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation, parallel design study to evaluate the safety, tolerability, and pharmacokinetics of IV rhu-pGSN or saline placebo administered as 5 doses each of 6, 12, 18, or 24 mg/kg of body weight. Each of 4 dosing cohorts will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects). Subjects will be healthy adult volunteers 18-55 years of age.
Detailed description
Doses will be administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4). Subjects will be kept in-house until after the last blood sample is taken on Day 5. Subjects will return for follow-up 7 days after the initiation of therapy (Day 8) and on Day 28 for the End-of-Study (EOS) Visit. After each cohort has completed the Day 8 visit, review of the safety results (including labs) will be conducted (and unblinded where appropriate) before the initiation of the next higher dose cohort. To assess safety and tolerability, subjects will undergo physical examinations (including vital sign measurements), adverse event (AE) assessments, concomitant medication assessments, and safety laboratory testing. Blood samples will be collected for analysis of pGSN levels and antibodies against pGSN.
Interventions
intravenous administration of either 6, 12, 18, or 24 mg/kg at time 0, 12, 36, 60 and 84 hours
OTHERplacebo
intravenous administration of saline control at time 0, 12, 36, 60 and 84 hours
Sponsors
BioAegis Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Doses prepared by unblinded pharmacist. Placebo and Drug are undistinguishable in syringe for administration.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female adults 18 to 55 years of age without chronic or active acute medical conditions 2. Informed consent obtained from subject 3. Weight ≤100 kg and body mass index (BMI) \<30 kg/m2 4. Willingness to use contraception during the course of the study, starting at screening and for at least 3 months after their final study treatment
Exclusion criteria
1. Pregnant or lactating women 2. Acute illness during the month prior to screening 3. Circumstances that may require any medications (including prescription medication, over-the-counter medication, vitamins, or supplements) during the during the inpatient days of the study other than acetaminophen 4. Hospitalization during the year prior to screening 5. History of cancer or treatment with systemic chemotherapy or radiation therapy at any time 6. Transplantation of hematopoietic or solid organs 7. History of diabetes mellitus; myocardial infarction, angina, or other cardiovascular disease; stroke or cerebrovascular disease; chronic obstructive pulmonary disease (COPD) or asthma; deep vein thrombosis (DVT)/pulmonary embolism (PE); liver or kidney disease; clinically significant psychiatric condition; or active or chronic infection 8. Receipt of blood products during the year prior to screening 9. Chronic mechanical ventilation or dialysis 10. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the Investigator 11. Any clinically significant abnormalities of vital signs, EKG or physical examination findings as judged by the Investigator 12. Positive results for recreational drugs during screening 13. Any other condition deemed by the Investigator as possibly interfering with the conduct of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 28 days | Number of subjects who had an Adverse Event |
| Serious Adverse Events | 28 days | Number of subjects who had a Serious Adverse Event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: pGSN Concentration | 108 hours | Concentration of pGSN at baseline, 12 hours after dose 1, and 24 hours after doses 2 and 5 |
| Pharmacokinetics: pGSN Area Under the Curve (AUC) | 108 hours | Area Under the Curve (AUC) of pGSN concentration at 12 hours after dose 1, and 24 hours after doses 2 and 5 |
| Pharmacokinetics: pGSN Half-life | 108 hours | Half-life of pGSN concentration 12 hours after dose 1, and 24 hours after doses 2 and 5 |
| Presence of Anti-drug Antibodies | 28 days | Number of participants who tested positive for anti-pGSN antibodies at baseline, and on day 28 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (6 mg/kg) IV rhu-pGSN administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4) | 6 |
| Cohort 2 (12 mg/kg) IV rhu-pGSN administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4) | 6 |
| Cohort 3 (18 mg/kg) IV rhu-pGSN administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4) | 6 |
| Cohort 4 (24 mg/kg) IV rhu-pGSN administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4) | 6 |
| Placebo Cohorts 1-4 Dosed at a weight-based volume of 0.025 mL/mg × dose in mg/kg × weight in kg of 0.9% saline solution via IV push (matching the volume of rhu-pGSN for a subject of that size) injected at ≤20 mL/minute though a standard 0.2 μ filter. Placebo was administered on the same schedule as the active drug. | 8 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 (6 mg/kg) | Cohort 2 (12 mg/kg) | Cohort 3 (18 mg/kg) | Cohort 4 (24 mg/kg) | Placebo Cohorts 1-4 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 34.0 years | 41.5 years | 36.0 years | 37.5 years | 28.5 years | 36.5 years |
| BMI | 24.55 kg/m^2 STANDARD_DEVIATION 2.899 | 24.77 kg/m^2 STANDARD_DEVIATION 3.506 | 25.28 kg/m^2 STANDARD_DEVIATION 3.722 | 25.43 kg/m^2 STANDARD_DEVIATION 2.876 | 23.85 kg/m^2 STANDARD_DEVIATION 2.021 | 24.72 kg/m^2 STANDARD_DEVIATION 2.862 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 5 Participants | 6 Participants | 5 Participants | 7 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 7 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 1 / 6 | 2 / 6 | 3 / 6 | 2 / 6 | 1 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Adverse Events
Number of subjects who had an Adverse Event
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (6 mg/kg) | Adverse Events | 1 Participants |
| Cohort 2 (12 mg/kg) | Adverse Events | 2 Participants |
| Cohort 3 (18 mg/kg) | Adverse Events | 3 Participants |
| Cohort 4 (24 mg/kg) | Adverse Events | 2 Participants |
| Placebo Cohorts 1-4 | Adverse Events | 1 Participants |
Primary
Serious Adverse Events
Number of subjects who had a Serious Adverse Event
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (6 mg/kg) | Serious Adverse Events | 0 Participants |
| Cohort 2 (12 mg/kg) | Serious Adverse Events | 0 Participants |
| Cohort 3 (18 mg/kg) | Serious Adverse Events | 0 Participants |
| Cohort 4 (24 mg/kg) | Serious Adverse Events | 0 Participants |
| Placebo Cohorts 1-4 | Serious Adverse Events | 0 Participants |
Secondary
Pharmacokinetics: pGSN Area Under the Curve (AUC)
Area Under the Curve (AUC) of pGSN concentration at 12 hours after dose 1, and 24 hours after doses 2 and 5
Time frame: 108 hours
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-12 (dose 1) | 1245.5 hours*(micrograms/mL) | Standard Deviation 257.9 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 5) | 3486.5 hours*(micrograms/mL) | Standard Deviation 1035.2 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 2) | 3066.2 hours*(micrograms/mL) | Standard Deviation 256.8 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-12 (dose 1) | 2737.5 hours*(micrograms/mL) | Standard Deviation 379.1 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 5) | 6599.1 hours*(micrograms/mL) | Standard Deviation 1334.2 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 2) | 6448.5 hours*(micrograms/mL) | Standard Deviation 599.5 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 2) | 9374.2 hours*(micrograms/mL) | Standard Deviation 2456 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-12 (dose 1) | 3547.0 hours*(micrograms/mL) | Standard Deviation 657.3 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 5) | 9139.1 hours*(micrograms/mL) | Standard Deviation 793.1 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-12 (dose 1) | 4832.3 hours*(micrograms/mL) | Standard Deviation 646.6 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 5) | 12135.3 hours*(micrograms/mL) | Standard Deviation 1172.4 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Area Under the Curve (AUC) | AUC0-24 (dose 2) | 10258.2 hours*(micrograms/mL) | Standard Deviation 2035.6 |
Secondary
Pharmacokinetics: pGSN Concentration
Concentration of pGSN at baseline, 12 hours after dose 1, and 24 hours after doses 2 and 5
Time frame: 108 hours
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Concentration | Baseline | 63.6 micrograms/mL | Standard Deviation 13.2 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 1) | 148.4 micrograms/mL | Standard Deviation 26.8 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 2) | 225.2 micrograms/mL | Standard Deviation 27 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 5) | 218.9 micrograms/mL | Standard Deviation 37.7 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 1) | 347.5 micrograms/mL | Standard Deviation 41.2 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 2) | 506.9 micrograms/mL | Standard Deviation 78.5 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 5) | 501.6 micrograms/mL | Standard Deviation 60.4 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Concentration | Baseline | 61.2 micrograms/mL | Standard Deviation 19.7 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 2) | 691.5 micrograms/mL | Standard Deviation 110.5 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 1) | 442.5 micrograms/mL | Standard Deviation 50.2 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 5) | 703.8 micrograms/mL | Standard Deviation 140.7 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Concentration | Baseline | 59.1 micrograms/mL | Standard Deviation 8.8 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 5) | 970.9 micrograms/mL | Standard Deviation 87.9 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 1) | 663.6 micrograms/mL | Standard Deviation 110.8 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Concentration | Baseline | 71.8 micrograms/mL | Standard Deviation 11.1 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Concentration | Cmax (Dose 2) | 855.7 micrograms/mL | Standard Deviation 200.6 |
Secondary
Pharmacokinetics: pGSN Half-life
Half-life of pGSN concentration 12 hours after dose 1, and 24 hours after doses 2 and 5
Time frame: 108 hours
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 1) | 14.0 hours | Standard Deviation 5.4 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 5) | 28.4 hours | Standard Deviation 8.5 |
| Cohort 1 (6 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 2) | 16.7 hours | Standard Deviation 6.1 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 1) | 13.1 hours | Standard Deviation 2.6 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 5) | 22.0 hours | Standard Deviation 11.3 |
| Cohort 2 (12 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 2) | 14.5 hours | Standard Deviation 3.4 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 2) | 15.1 hours | Standard Deviation 4.5 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 1) | 9.2 hours | Standard Deviation 3 |
| Cohort 3 (18 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 5) | 17.6 hours | Standard Deviation 1.9 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 1) | 10.7 hours | Standard Deviation 5.2 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 5) | 14.5 hours | Standard Deviation 2.2 |
| Cohort 4 (24 mg/kg) | Pharmacokinetics: pGSN Half-life | t1/2 (dose 2) | 12.0 hours | Standard Deviation 1.5 |
Secondary
Presence of Anti-drug Antibodies
Number of participants who tested positive for anti-pGSN antibodies at baseline, and on day 28
Time frame: 28 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (6 mg/kg) | Presence of Anti-drug Antibodies | Baseline | 0 Participants |
| Cohort 1 (6 mg/kg) | Presence of Anti-drug Antibodies | Day 28 | 0 Participants |
| Cohort 2 (12 mg/kg) | Presence of Anti-drug Antibodies | Baseline | 0 Participants |
| Cohort 2 (12 mg/kg) | Presence of Anti-drug Antibodies | Day 28 | 0 Participants |
| Cohort 3 (18 mg/kg) | Presence of Anti-drug Antibodies | Baseline | 0 Participants |
| Cohort 3 (18 mg/kg) | Presence of Anti-drug Antibodies | Day 28 | 0 Participants |
| Cohort 4 (24 mg/kg) | Presence of Anti-drug Antibodies | Day 28 | 1 Participants |
| Cohort 4 (24 mg/kg) | Presence of Anti-drug Antibodies | Baseline | 0 Participants |
| Placebo Cohorts 1-4 | Presence of Anti-drug Antibodies | Baseline | 0 Participants |
| Placebo Cohorts 1-4 | Presence of Anti-drug Antibodies | Day 28 | 1 Participants |