Healthy
Conditions
Keywords
ALT-803, PK
Brief summary
This is a single center, open-label, pharmacokinetic study of ALT-803 administered as a subQ injection to healthy volunteers.
Interventions
DRUGALT-803
Subjects randomized to Group A will receive ALT-803 at a concentration of 1.0 mg/mL and subjects randomized to Group B will receive ALT-803 at a concentration of 2.0 mg/mL. Subjects will receive a single 10 µg/kg subQ dose of ALT-803 on Day 1 of study period 1. After a rest period, subjects will receive a single 20 µg/kg subQ dose of ALT-803 on Day 1 of study period 2.
Sponsors
Altor BioScience
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed Written Informed Consent 1. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of subject care. 2. Subjects must be willing and able to comply with the scheduled visits, study drug dosing schedule, procedures, laboratory tests, and other requirements of the study. 2. Study Population 1. Body mass index (BMI) must be within the range of 18 to 28 kg/m2. Subjects must weigh between 50 and 100 kg (inclusive). 2. Subjects must be in good health as determined by past medical history, complete physical examination, vital signs and laboratory tests at screening. 3. Age and Reproductive Status 1. Men and women, 18 - 65 years of age. 2. Female participants of childbearing potential must adhere to using a medically accepted method of birth control up to 28 days prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) WOCBP must agree to use effective contraception during the study and for at least 1 month following the last dose of the study drug. 3. WOCBP must have a negative serum pregnancy test \< 14 days prior to first dose of the study drug. Non-childbearing is defined as greater than one year postmenopausal or surgically sterilized. 4. Male subjects must be willing to use barrier contraception (i.e. condoms and spermicide) from the day of dosing until at least 1 month following the last dose of study drug.
Exclusion criteria
1. Medical History and Concurrent Diseases 1. A past medical history of clinically significant 12 lead EKG abnormalities 2. Subjects with a history of interstitial lung disease and/or pneumonitis. 3. HIV-positive. 4. Significant illness within 2 weeks prior to dosing. 5. Positive hepatitis C serology or active hepatitis B infection. 6. Known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 4 weeks or 5 half-lives of registration are excluded. 7. Psychiatric illness/social situations that would limit compliance with study requirements. 8. Previous malignancies, unless basal or squamous cell carcinoma of the skin or cervical carcinoma in situ with a complete remission achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period. 9. Loss of ≥ 475 mL blood volume or blood donation transfusion of any blood product within 3 months prior to screening. 10. Other illness or laboratory abnormality that in the opinion of the Investigator should exclude the subject from participating in this study. 2. Prohibited Treatments and/or Restricted Therapies 1. Use of any prescription drugs within 4 weeks (hormonal methods of contraception are allowed) or less than 5 half-lives prior to dosing, or over-the-counter (OTC) medication (vitamins, herbal supplements, dietary supplements) within 2 weeks or less than 5 half-lives prior to dosing. 2. Exposure to any investigational drug or placebo within 3 months of first dose of study drug. 3. Previous treatment or clinical trial participation with monoclonal antibody therapy. 4. History of drug or alcohol abuse within 12 months prior to dosing, or those who have a positive urine drug test or breath alcohol test at Screening or Baseline. 5. Transfusion of blood or any blood product within 3 months prior to screening. 6. History of using nicotine-containing products or smoking more than 5 cigarettes weekly for at least three months prior to the study through the final evaluation. 3. Allergies and Adverse Drug Reaction 1. History of severe hypersensitivity reactions to other monoclonal antibodies. 2. Known history of clinically significant drug allergy at Screening or Baseline 4. Sex and Reproductive Status a. Women who are pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Profile - Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | Up to 192 hours | area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf) |
| PK Profile - Time of the Observed Maximum Concentration (Tmax) | Up to 192 hours | time of the observed maximum concentration (Tmax) |
| PK Profile - Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | Up to 192 hours | area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t) |
| PK Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | Up to 192 hours | Apparent volume of distribution is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration. |
| PK Profile - Apparent (Extravascular) Clearance (CL/F) | Up to 192 hours | apparent (extravascular) clearance (CL/F) |
| PK Profile - Maximum Observed Concentration (Cmax) | Up to 192 hours | maximum observed concentration (Cmax) |
| PK Profile - Half-life (t½) | Up to 192 hours | The period of time required for the concentration or amount of drug in the body to be reduced by one-half. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Up to 66 days | Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A 1.0 mg/ml ALT-803
ALT-803: Subjects randomized to Group A will receive ALT-803 at a concentration of 1.0 mg/mL. Subjects will receive a single 10 µg/kg subQ dose of ALT-803 on Day 1 of study period 1. After a rest period, subjects will receive a single 20 µg/kg subQ dose of ALT-803 on Day 1 of study period 2. | 10 |
| Group B 2.0 mg/ml ALT-803
ALT-803: Subjects randomized to Group B will receive ALT-803 at a concentration of 2.0 mg/mL. Subjects will receive a single 10 µg/kg subQ dose of ALT-803 on Day 1 of study period 1. After a rest period, subjects will receive a single 20 µg/kg subQ dose of ALT-803 on Day 1 of study period 2. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 11.3 | 42.5 years STANDARD_DEVIATION 11.6 | 44 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 10 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Healthy Volunteers | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
PK Profile - Apparent (Extravascular) Clearance (CL/F)
apparent (extravascular) clearance (CL/F)
Time frame: Up to 192 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | PK Profile - Apparent (Extravascular) Clearance (CL/F) | Period 1 - 10 µg/kg | 8650 mL/day/kg | Standard Deviation 5450 |
| Group A | PK Profile - Apparent (Extravascular) Clearance (CL/F) | Period 2 - 20 µg/kg | 10500 mL/day/kg | Standard Deviation 5430 |
| Group B | PK Profile - Apparent (Extravascular) Clearance (CL/F) | Period 1 - 10 µg/kg | 6610 mL/day/kg | Standard Deviation 2680 |
| Group B | PK Profile - Apparent (Extravascular) Clearance (CL/F) | Period 2 - 20 µg/kg | 11000 mL/day/kg | Standard Deviation 4440 |
Primary
PK Profile - Apparent (Extravascular) Volume of Distribution (Vz/F)
Apparent volume of distribution is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration.
Time frame: Up to 192 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | PK Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | Period 1 - 10 μg/kg | 13900 mL/kg | Standard Deviation 12000 |
| Group A | PK Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | Period 2 - 20 μg/kg | 15500 mL/kg | Standard Deviation 13000 |
| Group B | PK Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | Period 1 - 10 μg/kg | 5360 mL/kg | Standard Deviation 2790 |
| Group B | PK Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | Period 2 - 20 μg/kg | 11800 mL/kg | Standard Deviation 8170 |
Primary
PK Profile - Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf)
area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf)
Time frame: Up to 192 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | Period 1 - 10 µg/kg | 1600 Day*pg/mL | Standard Deviation 897 |
| Group A | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | Period 2 - 20 µg/kg | 2420 Day*pg/mL | Standard Deviation 1400 |
| Group B | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | Period 1 - 10 µg/kg | 1740 Day*pg/mL | Standard Deviation 731 |
| Group B | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | Period 2 - 20 µg/kg | 2130 Day*pg/mL | Standard Deviation 1000 |
Primary
PK Profile - Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t)
area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t)
Time frame: Up to 192 hours
Population: In Period 2, 3 participants in each arm dropped off the study. In Group A, the 1 additional participant was excluded from the analysis. Subject 0317-001-0020 samples were Not Calculated for Period 1, but they were calculated for Period 2. Hence, the number of subjects with samples was greater in Period 2 than in Period 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | Period 1 - 10 µg/kg | 1390 Day*pg/mL | Standard Deviation 727 |
| Group A | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | Period 2 - 20 µg/kg | 2370 Day*pg/mL | Standard Deviation 1410 |
| Group B | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | Period 1 - 10 µg/kg | 1240 Day*pg/mL | Standard Deviation 706 |
| Group B | PK Profile - Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | Period 2 - 20 µg/kg | 1940 Day*pg/mL | Standard Deviation 1040 |
Primary
PK Profile - Half-life (t½)
The period of time required for the concentration or amount of drug in the body to be reduced by one-half.
Time frame: Up to 192 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | PK Profile - Half-life (t½) | Period 1 (10 μg/kg) | 1.07 Days | Standard Deviation 0.813 |
| Group A | PK Profile - Half-life (t½) | Period 2 (20 μg/kg) | 1.02 Days | Standard Deviation 0.758 |
| Group B | PK Profile - Half-life (t½) | Period 1 (10 μg/kg) | 0.55 Days | Standard Deviation 0.095 |
| Group B | PK Profile - Half-life (t½) | Period 2 (20 μg/kg) | 0.68 Days | Standard Deviation 0.236 |
Primary
PK Profile - Maximum Observed Concentration (Cmax)
maximum observed concentration (Cmax)
Time frame: Up to 192 hours
Population: In Period 2, 3 participants in each arm dropped off the study. In Group A, the 1 additional participant was excluded from the analysis. Subject 0317-001-0020 samples were Not Calculated for Period 1, but they were calculated for Period 2. Hence, the number of subjects with samples was greater in Period 2 than in Period 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | PK Profile - Maximum Observed Concentration (Cmax) | Period 1 - 10 µg/kg | 1150 pg/mL | Standard Deviation 945 |
| Group A | PK Profile - Maximum Observed Concentration (Cmax) | Period 2 - 20 µg/kg | 1900 pg/mL | Standard Deviation 1930 |
| Group B | PK Profile - Maximum Observed Concentration (Cmax) | Period 1 - 10 µg/kg | 1080 pg/mL | Standard Deviation 902 |
| Group B | PK Profile - Maximum Observed Concentration (Cmax) | Period 2 - 20 µg/kg | 1490 pg/mL | Standard Deviation 921 |
Primary
PK Profile - Time of the Observed Maximum Concentration (Tmax)
time of the observed maximum concentration (Tmax)
Time frame: Up to 192 hours
Population: In Period 2, 3 participants in each arm dropped off the study. In Group A, the 1 additional participant was excluded from the analysis. Subject 0317-001-0020 samples were Not Calculated for Period 1, but they were calculated for Period 2. Hence, the number of subjects with samples was greater in Period 2 than in Period 1.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A | PK Profile - Time of the Observed Maximum Concentration (Tmax) | Period 1 - 10 µg/kg | 0.167 Days |
| Group A | PK Profile - Time of the Observed Maximum Concentration (Tmax) | Period 2 - 20 µg/kg | 1.00 Days |
| Group B | PK Profile - Time of the Observed Maximum Concentration (Tmax) | Period 1 - 10 µg/kg | 0.583 Days |
| Group B | PK Profile - Time of the Observed Maximum Concentration (Tmax) | Period 2 - 20 µg/kg | 0.170 Days |
Secondary
Number of Adverse Events
Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Time frame: Up to 66 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Adverse Events | 10 Participants |
| Group B | Number of Adverse Events | 10 Participants |