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

NCT ID: NCT01660230

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2012-12-31

Brief 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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

6 µg/kg 3K3A-APC, single-dose

Cohort 1: 6 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 20 mL IV infusion over 15 minutes

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

30 µg/kg 3K3A-APC, single-dose

Cohort 2: 30 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

90 µg/kg 3K3A-APC, single-dose

Cohort 3: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

180 µg/kg 3K3A-APC, single-dose

Cohort 4: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

360 µg/kg 3K3A-APC, single-dose

Cohort 5: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

TBD µg/kg 3K3A-APC, single-dose

Cohort 6: TBD (not to exceed 720) µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

90 µg/kg 3K3A-APC, q12h for 5 doses

Cohort 7: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

180 µg/kg 3K3A-APC, q12h for 5 doses

Cohort 8: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

360 µg/kg 3K3A-APC, q12h for 5 doses

Cohort 9: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

TBD µg/kg 3K3A-APC, q12h for 5 doses

Cohort 10: TBD (not to exceed 720) µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses

Group Type: ACTIVE_COMPARATOR

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

Matching Placebo, 0.9% NaCl in water

Cohorts 1-10: 0.9% sodium chloride in water and administered as either 20 mL IV infusion over 15 minutes (Cohort 1), or 100 mL IV infusion over 15 minutes (Cohorts 2-10)

Group Type: PLACEBO_COMPARATOR

0.9% NaCl in water

Intervention Type: DRUG

Interventions

3K3A-APC, diluted in 0.9% sodium chloride in water

Intervention Type: BIOLOGICAL

0.9% NaCl in water

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ZZ Biotech, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick D Lyden, MD, FAAN

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Howard Levy, MD, PhD, MMM

Role: STUDY_DIRECTOR

ZZ Biotech, LLC

Locations

Privatklinik Leech

Graz, , Austria

Countries

Austria

References

Lyden P, Levy H, Weymer S, Pryor K, Kramer W, Griffin JH, Davis TP, Zlokovic B. Phase 1 safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers. Curr Pharm Des. 2013;19(42):7479-85. doi: 10.2174/1381612819666131230131454.

Reference Type: DERIVED

PMID: 24372304 (View on PubMed)

Other Identifiers

2011-000793-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ZZ-3K3A-001

Identifier Type: -

Identifier Source: org_study_id