QUILT-1.004: A Single Center, Open-label, Pharmacokinetic Study of Subcutaneous ALT-803

Study Overview
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Brief Summary
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This is a single center, open-label, pharmacokinetic study of ALT-803 administered as a subQ injection to healthy volunteers.

Official Title
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QUILT-1.004: A Single Center, Open-label, Pharmacokinetic Study of Subcutaneous ALT-803

Conditions
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Healthy

Intervention / Treatment
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* Drug: ALT-803


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Written Informed Consent 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. 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. Study Population Body mass index (BMI) must be within the range of 18 to 28 kg/m2. Subjects must weigh between 50 and 100 kg (inclusive). Subjects must be in good health as determined by past medical history, complete physical examination, vital signs and laboratory tests at screening. Age and Reproductive Status Men and women, 18 - 65 years of age. 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. 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. 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: Medical History and Concurrent Diseases A past medical history of clinically significant 12 lead EKG abnormalities Subjects with a history of interstitial lung disease and/or pneumonitis. HIV-positive. Significant illness within 2 weeks prior to dosing. Positive hepatitis C serology or active hepatitis B infection. 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. Psychiatric illness/social situations that would limit compliance with study requirements. 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. Loss of ≥ 475 mL blood volume or blood donation transfusion of any blood product within 3 months prior to screening. Other illness or laboratory abnormality that in the opinion of the Investigator should exclude the subject from participating in this study. Prohibited Treatments and/or Restricted Therapies 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. Exposure to any investigational drug or placebo within 3 months of first dose of study drug. Previous treatment or clinical trial participation with monoclonal antibody therapy. 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. Transfusion of blood or any blood product within 3 months prior to screening. 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. Allergies and Adverse Drug Reaction History of severe hypersensitivity reactions to other monoclonal antibodies. Known history of clinically significant drug allergy at Screening or Baseline Sex and Reproductive Status a. Women who are pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>1.0 mg/ml ALT-803 | Drug: ALT-803<br>* Subjects randomized to Group A (n=8) will receive ALT-803 at a concentration of 1.0 mg/mL and subjects randomized to Group B (n=8) 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.<br>|
| Experimental: Group B<br>2.0 mg/ml ALT-803 | Drug: ALT-803<br>* Subjects randomized to Group A (n=8) will receive ALT-803 at a concentration of 1.0 mg/mL and subjects randomized to Group B (n=8) 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile | half-life (t½) | 192 hours | 
| PK profile | apparent (extravascular) volume of distribution (Vz/F) | 192 hours | 
| PK profile | apparent (extravascular) clearance (CL/F) | 192 hours | 
| PK profile | maximum observed concentration (Cmax) | 192 hours | 
| PK profile | time of the observed maximum concentration (Tmax) | 192 hours | 
| PK profile | area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t) | 192 hours | 
| PK profile | area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf) | 192 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety as measured by the incidence and severity of adverse events. | 24 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALT-803, PK