Patient case: 47-year-old male with melanoma; genetic feature: APC loss of function

Clinical trial: Safety and Pharmacokinetics of Single and Multiple Ascending Doses of 3K3A-APC in Healthy Adult Volunteers

Summary: The purpose of this study is to evaluate the safety and pharmacokinetic profile of single and multiple ascending intravenous doses of 3K3A-APC in healthy adult subjects aged 18-55 years.

Detailed description: This is a single-center, sequential-cohort, double-blind, placebo-controlled, single- and multiple-ascending dose study. Eligible adult subjects will be assigned sequentially to 1 of 10 cohorts, at successively higher single doses, followed by successively higher multiple doses.
  Single IV Doses: 5 subjects per cohort, aged 18-55, will be randomized in a 4:1 manner to receive active drug (6, 30, 90, 180, 360, and TBD µg/kg) or to receive matching placebo (Cohorts 1-6).
  Multiple IV Doses: 8 subjects per cohort, aged 18-55, will be randomized in a 3:1 manner to receive active drug (90, 180, 360, and TBD µg/kg) or to receive matching placebo every 12 hours for 5 doses (Cohorts 7-10).
  Single-Dose Cohorts Subjects receiving a single dose will be confined in a Phase 1 unit for 12 hours prior to dosing, during dosing, and for 24 hours after dosing (Study Day 1-2) for observation and PK sampling. Subjects will return on Study Day 4 (~72 hours after infusion) and Study Day 15 for additional safety evaluations. A 28-Day follow-up phone call will be made to subjects to collect AEs that occur within 28-days of the dose.
  Multiple-Dose Cohorts Subjects receiving multiple doses will be confined in a Phase 1 unit for 12 hours prior to dosing through 24 hours following the last dose (Study Day 1-4) for observation and PK sampling. Subjects will return on Study Day 6 (~72 hours after last infusion) and Study Day 15 for additional safety evaluations. A 28-Day follow-up phone call will be made to subjects to collect AEs that occur within 28-days of the last dose.

Eligibility: Inclusion Criteria:
  1. Healthy males or non-pregnant, non-lactating females
  2. Both men and women of child-bearing potential (i.e., not surgically sterile or post-menopausal defined as age > 40 years without menses for ≥ 2 years) must agree to use a barrier method of contraception plus a spermicide throughout the study.
  3. Age 18 to 55 years, inclusive
  4. Body Mass Index (BMI) of 19 to 30 kg/m2, inclusive (see APPENDIX B)
  5. Willing and able to complete all study visits
  6. Agreement to abstain from smoking and drinking alcoholic beverages from 48 hours prior to randomization through last Study Day (15)
  7. Signed informed consent form (ICF)
  Exclusion Criteria:
  1. Any medical problem for which the subject is being evaluated and/or treated
  2. Activated partial thromboplastin time (aPTT) greater than upper limit of normal (ULN)
  3. Platelet count < 125,000 cells/mm3
  4. International Normalized Ratio (INR) > 1.3
  5. Any other clinically significant abnormalities in laboratory values (chemistries, hematology, coagulation studies, and urinalysis - see APPENDIX C)
  6. Clinically significant abnormalities on electrocardiogram (ECG)
  7. Positive serum βHCG pregnancy test at screening or on Study Day -1 (for all women, regardless of child-bearing potential)
  8. Positive urine drug screen at screening or on Study Day -1 (see APPENDIX C)
  9. Positive blood test for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody
  10. Known family history of bleeding or blood clotting disorders
  11. History of bleeding diathesis
  12. History of liver disease with ongoing coagulopathy
  13. Use of any prescription or non-prescription medications or supplements within 7 days prior to Study Day -1, excluding hormonal contraceptives
  14. Use of anticoagulant medication within 14 days prior to Study Day -1
  15. Major surgery within 60 days prior to Study Day -1
  16. Receipt of an investigational drug within 30 days prior to Study Day -1
  17. Donation of blood or plasma within 30 days prior to Study Day -1
  18. Any other condition, that in the opinion of the Site Investigator, may adversely affect the safety of the subject, the subject's ability to complete the study, or the outcome of the study

Relevance to patient case: not relevant