NCT01660230

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
64

participants targeted

Target at P75+ for phase_1 healthy

Timeline
Completed

Started Aug 2012

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 25, 2012

Completed
7 days until next milestone

Study Start

First participant enrolled

August 1, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 8, 2012

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

April 10, 2014

Completed
Last Updated

February 5, 2018

Status Verified

January 1, 2018

Enrollment Period

4 months

First QC Date

July 25, 2012

Results QC Date

February 27, 2014

Last Update Submit

January 9, 2018

Conditions

Healthy

Keywords

APC, 3K3A, 3K3A-APC, volunteer, healthy

Outcome Measures

Primary Outcomes (2)

  • Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol.

    Day 4 for single-dose cohorts

  • Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in the Protocol.

    Day 6 for multiple-dose cohorts

Secondary Outcomes (20)

  • Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Non-compartmental Analysis

    0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

  • Time at Which Cmax is Observed (Tmax) for 3K3A-APC by Non-compartmental Analysis

    0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

  • Area Under the Plasma Concentration-time Curve From Time 0 to the Final Time With a Concentration ≥ Limit of Quantitation [AUC(0-t)] for 3K3A-APC by Non-compartmental Analysis

    0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

  • Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Non-compartmental Analysis

    0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

  • Elimination Rate Constant (λz) for 3K3A-APC by Non-compartmental Analysis

    0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose

  • +15 more secondary outcomes

Study Arms (11)

6 µg/kg 3K3A-APC, single-dose

ACTIVE COMPARATOR

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

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

30 µg/kg 3K3A-APC, single-dose

ACTIVE COMPARATOR

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

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

90 µg/kg 3K3A-APC, single-dose

ACTIVE COMPARATOR

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

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

180 µg/kg 3K3A-APC, single-dose

ACTIVE COMPARATOR

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

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

360 µg/kg 3K3A-APC, single-dose

ACTIVE COMPARATOR

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

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

TBD µg/kg 3K3A-APC, single-dose

ACTIVE COMPARATOR

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

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

90 µg/kg 3K3A-APC, q12h for 5 doses

ACTIVE COMPARATOR

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

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

180 µg/kg 3K3A-APC, q12h for 5 doses

ACTIVE COMPARATOR

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

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

360 µg/kg 3K3A-APC, q12h for 5 doses

ACTIVE COMPARATOR

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

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

TBD µg/kg 3K3A-APC, q12h for 5 doses

ACTIVE COMPARATOR

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

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

Matching Placebo, 0.9% NaCl in water

PLACEBO COMPARATOR

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)

Drug: 0.9% NaCl in water

Interventions

3K3A-APC, diluted in 0.9% sodium chloride in waterBIOLOGICAL
180 µg/kg 3K3A-APC, q12h for 5 doses180 µg/kg 3K3A-APC, single-dose30 µg/kg 3K3A-APC, single-dose360 µg/kg 3K3A-APC, q12h for 5 doses360 µg/kg 3K3A-APC, single-dose6 µg/kg 3K3A-APC, single-dose90 µg/kg 3K3A-APC, q12h for 5 doses90 µg/kg 3K3A-APC, single-doseTBD µg/kg 3K3A-APC, q12h for 5 dosesTBD µg/kg 3K3A-APC, single-dose
0.9% NaCl in waterDRUG
Matching Placebo, 0.9% NaCl in water

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy males or non-pregnant, non-lactating females
  • 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.
  • Age 18 to 55 years, inclusive
  • Body Mass Index (BMI) of 19 to 30 kg/m2, inclusive (see APPENDIX B)
  • Willing and able to complete all study visits
  • Agreement to abstain from smoking and drinking alcoholic beverages from 48 hours prior to randomization through last Study Day (15)
  • Signed informed consent form (ICF)

You may not qualify if:

  • Any medical problem for which the subject is being evaluated and/or treated
  • Activated partial thromboplastin time (aPTT) greater than upper limit of normal (ULN)
  • Platelet count \< 125,000 cells/mm3
  • International Normalized Ratio (INR) \> 1.3
  • Any other clinically significant abnormalities in laboratory values (chemistries, hematology, coagulation studies, and urinalysis - see APPENDIX C)
  • Clinically significant abnormalities on electrocardiogram (ECG)
  • Positive serum βHCG pregnancy test at screening or on Study Day -1 (for all women, regardless of child-bearing potential)
  • Positive urine drug screen at screening or on Study Day -1 (see APPENDIX C)
  • Positive blood test for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody
  • Known family history of bleeding or blood clotting disorders
  • History of bleeding diathesis
  • History of liver disease with ongoing coagulopathy
  • Use of any prescription or non-prescription medications or supplements within 7 days prior to Study Day -1, excluding hormonal contraceptives
  • Use of anticoagulant medication within 14 days prior to Study Day -1
  • Major surgery within 60 days prior to Study Day -1
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Privatklinik Leech

Graz, 8010, Austria

Location

Related Publications (1)

  • 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.

    PMID: 24372304DERIVED

MeSH Terms

Interventions

Sodium ChlorideWater

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium CompoundsHydroxidesAlkaliesAnionsIonsElectrolytesOxidesOxygen Compounds

Limitations and Caveats

Samples were analyzed from 4 treated subjects in the 6 μg/kg dose group, but all values were below the lower limit of quantitation for the assay (75 ng/mL) and therefore no PK analysis could be performed.

Results Point of Contact

Title
Kent Pryor, PhD, MBA, Chief Operating Officer
Organization
ZZ Biotech, LLC
kpryor@zzbiotech.com

Study Officials

  • Patrick D Lyden, MD, FAAN

    Cedars-Sinai Medical Center

    PRINCIPAL INVESTIGATOR

  • Howard Levy, MD, PhD, MMM

    ZZ Biotech, LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 25, 2012

First Posted

August 8, 2012

Study Start

August 1, 2012

Primary Completion

December 1, 2012

Study Completion

December 1, 2012

Last Updated

February 5, 2018

Results First Posted

April 10, 2014

Record last verified: 2018-01

Locations

AU(1)