HealthyPhase 1NCT01660230

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

A Phase 1 study testing 3K3A-APC, diluted in 0.9% sodium chloride in water and 0.9% NaCl in water in people with Healthy, run by ZZ Biotech, LLC at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: 3K3A-APC, diluted in 0.9% sodium chloride in water and 0.9% NaCl in water
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 64 participants
Where: 1 siteAustria
Study dates: Aug 2012to Dec 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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)

Who cannot join

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)

Show all 18Show fewer

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
Receipt of an investigational drug within 30 days prior to Study Day -1
Donation of blood or plasma within 30 days prior to Study Day -1
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

Trial locations and contacts

1 site in 1 country.

Austria1 site

Privatklinik Leech
Graz, 8010

Other trials in Austria

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of 3K3A-APC, a Recombinant Variant of Human Activated Protein C (APC), in Healthy Adult Volunteers

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.

Read the 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
Being tested: 3K3A-APC, diluted in 0.9% sodium chloride in water, 0.9% NaCl in water
Keywords: APC, 3K3A, 3K3A-APC, volunteer, healthy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

3K3A-APC, diluted in 0.9% sodium chloride in waterBiological
0.9% NaCl in waterDrug

Study groups in NCT01660230
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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) Receives: Drug: 0.9% NaCl in water

What is being measured

The primary outcome is the main question the study is designed to answer.

Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol.
Measured: Day 4 for single-dose cohorts
Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in the Protocol.
Measured: Day 6 for multiple-dose cohorts

Secondary outcomes (20)

Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Non-compartmental Analysis
Single-dose cohorts
Measured: 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
Single-dose cohorts
Measured: 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
Single-dose cohorts
Measured: 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
Single-dose cohorts
Measured: 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
Single-dose cohorts
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Half-life (t1/2) of 3K3A-APC by Non-compartmental Analysis
Single-dose cohorts
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Total Clearance (CL) of 3K3A-APC by Non-compartmental Analysis
Single-dose cohorts
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Volume of Distribution (Vz) of 3K3A-APC by Non-compartmental Analysis
Single-dose cohorts
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis
Single-dose cohorts
Measured: 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 Compartmental Analysis
Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 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 Compartmental Analysis
Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Half-life (t1/2) of 3K3A-APC by Compartmental Analysis
Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Total Clearance (CL) of 3K3A-APC by Compartmental Analysis
Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis
Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis
Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 20 minutes and 1 hour post for doses 1 and 5
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Compartmental Analysis
Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 20 minutes and 1 hour post for doses 1 and 5
Elimination Rate Constant (λz) for 3K3A-APC by Compartmental Analysis
Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 20 minutes and 1 hour post for doses 1 and 5
Half-life (t1/2) of 3K3A-APC by Compartmental Analysis
Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 20 minutes and 1 hour post for doses 1 and 5
Total Clearance (CL) of 3K3A-APC by Compartmental Analysis
Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 20 minutes and 1 hour post for doses 1 and 5
Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis
Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Measured: 0, 20 minutes and 1 hour post for doses 1 and 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2012Dec 2012

First posted8 Aug 2012 (estimated)
Study startAug 2012
Primary completionDec 2012
Study completionDec 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01660230
Sponsor's protocol ID: ZZ-3K3A-001
Other IDs: 2011-000793-60
Status last verified: Jan 2018
First submitted: 25 Jul 2012
Last updated: 5 Feb 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 24372304

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of 3K3A-APC, a Recombinant Variant of Human Activated Protein C (APC), in Healthy Adult Volunteers
ClinicalTrials.gov ID: NCT01660230
Acronym / sponsor ID: ZZ-3K3A-001
Conditions: Healthy
Keywords: APC, 3K3A, 3K3A-APC, volunteer, healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: ZZ Biotech, LLCIndustry (pharma, biotech, devices)
Study start: Aug 2012
Primary completion: Dec 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 8 Aug 2012 (estimated)
Results: Posted 10 Apr 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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).

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 11

Arm	Type	Receives
6 µg/kg 3K3A-APC, single-dose	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
30 µg/kg 3K3A-APC, single-dose	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
90 µg/kg 3K3A-APC, single-dose	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
180 µg/kg 3K3A-APC, single-dose	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
360 µg/kg 3K3A-APC, single-dose	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
TBD µg/kg 3K3A-APC, single-dose	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
90 µg/kg 3K3A-APC, q12h for 5 doses	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
180 µg/kg 3K3A-APC, q12h for 5 doses	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
360 µg/kg 3K3A-APC, q12h for 5 doses	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
TBD µg/kg 3K3A-APC, q12h for 5 doses	Active comparator	Biological: 3K3A-APC, diluted in 0.9% sodium chloride in waterCohort 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
Matching Placebo, 0.9% NaCl in water	Placebo comparator	Drug: 0.9% NaCl in waterCohorts 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)

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (18 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
3K3A-APC, diluted in 0.9% sodium chloride in water	Biological	180 µg/kg 3K3A-APC, q12h for 5 doses, 180 µg/kg 3K3A-APC, single-dose, 30 µg/kg 3K3A-APC, single-dose, 360 µg/kg 3K3A-APC, q12h for 5 doses, 360 µg/kg 3K3A-APC, single-dose, 6 µg/kg 3K3A-APC, single-dose, 90 µg/kg 3K3A-APC, q12h for 5 doses, 90 µg/kg 3K3A-APC, single-dose, TBD µg/kg 3K3A-APC, q12h for 5 doses, TBD µg/kg 3K3A-APC, single-dose
0.9% NaCl in water	Drug	Matching Placebo, 0.9% NaCl in water

Primary outcome

Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol.
Time frame: Day 4 for single-dose cohorts
Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in the Protocol.
Time frame: Day 6 for multiple-dose cohorts

20 secondary outcomes

Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Non-compartmental Analysis
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Half-life (t1/2) of 3K3A-APC by Non-compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Total Clearance (CL) of 3K3A-APC by Non-compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Volume of Distribution (Vz) of 3K3A-APC by Non-compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis
Time frame: 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 Compartmental Analysis
Time frame: 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 Compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Half-life (t1/2) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Total Clearance (CL) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 20 minutes and 1 hour post for doses 1 and 5
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Compartmental Analysis
Time frame: 0, 20 minutes and 1 hour post for doses 1 and 5
Elimination Rate Constant (λz) for 3K3A-APC by Compartmental Analysis
Time frame: 0, 20 minutes and 1 hour post for doses 1 and 5
Half-life (t1/2) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 20 minutes and 1 hour post for doses 1 and 5
Total Clearance (CL) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 20 minutes and 1 hour post for doses 1 and 5
Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis
Time frame: 0, 20 minutes and 1 hour post for doses 1 and 5

Results and safety

Results posted to the registry on 10 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
6 µg/kg 3K3A-APC, Single-dose	4	4
30 µg/kg 3K3A-APC, Single-dose	4	4
90 µg/kg 3K3A-APC, Single-dose	4	4
180 µg/kg 3K3A-APC, Single-dose	4	4
360 µg/kg 3K3A-APC, Single-dose	4	4
720 µg/kg 3K3A-APC, Single-dose	2	2
540 µg/kg 3K3A-APC, Single-dose	4	4
90 µg/kg 3K3A-APC, q12h for 5 Doses	6	6
180 µg/kg 3K3A-APC, q12h for 5 Doses	6	6
360 µg/kg 3K3A-APC, q12h for 5 Doses	6	6
540 µg/kg 3K3A-APC, q12h for 5 Doses	6	6
Matching Placebo, 0.9% NaCl in Water	14	14

Primary outcome: Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol.

Time frame: Day 4 for single-dose cohorts. Number. Unit: participants

Measure	6 µg/kg 3K3A-APC, Single-dose n = 4	30 µg/kg 3K3A-APC, Single-dose n = 4	90 µg/kg 3K3A-APC, Single-dose n = 4	180 µg/kg 3K3A-APC, Single-dose n = 4	360 µg/kg 3K3A-APC, Single-dose n = 4	720 µg/kg 3K3A-APC, Single-dose n = 2	540 µg/kg 3K3A-APC, Single-dose n = 4	Matching Placebo, 0.9% NaCl in Water n = 6
Value	0	0	0	0	0	0	0	0

Population analysed: All 'single-dose' subjects who received at least one dose of study treatment.

Primary outcome: Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in the Protocol.

Time frame: Day 6 for multiple-dose cohorts. Number. Unit: participants

Measure	90 µg/kg 3K3A-APC, q12h for 5 Doses n = 6	180 µg/kg 3K3A-APC, q12h for 5 Doses n = 6	360 µg/kg 3K3A-APC, q12h for 5 Doses n = 6	540 µg/kg 3K3A-APC, q12h for 5 Doses n = 6	Matching Placebo, 0.9% NaCl in Water n = 8
Value	0	0	0	0	0

Population analysed: All 'multiple-dose' subjects who received at least one dose of study treatment.

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were reported from the first dose of study drug through 28 Days following the last dose (Day 28 Follow-up visit).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
6 µg/kg 3K3A-APC, Single-dose	0 of 4 (0%)	0 of 4 (0%)	Not reported
30 µg/kg 3K3A-APC, Single-dose	0 of 4 (0%)	2 of 4 (50%)	Not reported
90 µg/kg 3K3A-APC, Single-dose	0 of 4 (0%)	0 of 4 (0%)	Not reported
180 µg/kg 3K3A-APC, Single-dose	0 of 4 (0%)	1 of 4 (25%)	Not reported
360 µg/kg 3K3A-APC, Single-dose	0 of 4 (0%)	3 of 4 (75%)	Not reported
720 µg/kg 3K3A-APC, Single-dose	0 of 2 (0%)	2 of 2 (100%)	Not reported
540 µg/kg 3K3A-APC, Single-dose	0 of 4 (0%)	4 of 4 (100%)	Not reported
90 µg/kg 3K3A-APC, q12h for 5 Doses	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
180 µg/kg 3K3A-APC, q12h for 5 Doses	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
360 µg/kg 3K3A-APC, q12h for 5 Doses	0 of 6 (0%)	6 of 6 (100%)	Not reported
540 µg/kg 3K3A-APC, q12h for 5 Doses	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
Matching Placebo, 0.9% NaCl in Water	0 of 14 (0%)	6 of 14 (42.9%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24372304Lyden 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Patrick D Lyden, MD, FAAN principal investigator

Cedars-Sinai Medical Center

Howard Levy, MD, PhD, MMM study director

ZZ Biotech, LLC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 3K3A-APC, diluted in 0.9% sodium chloride in water and 0.9% NaCl in water in people with Healthy, run by ZZ Biotech, LLC at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol. (time frame: Day 4 for single-dose cohorts). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01660230, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018; AzTrials last refreshed its copy on 7 Nov 2026.