ThrombosisPhase 1NCT03453060

Safety and Tolerability Study of E-WE Thrombin in Healthy Adult Subjects

A Phase 1 study testing E-WE Thrombin- Dose 1, E-WE Thrombin- Dose 2 and E-WE Thrombin- Dose 3 in people with Thrombosis, run by Aronora, Inc. at 1 site in United States.

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 assess the safety, tolerability and pharmacodynamics of a single iv dose of E-WE Thrombin in healthy adult subjects. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Thrombosis
What is being tested?: E-WE Thrombin- Dose 1, E-WE Thrombin- Dose 2 and E-WE Thrombin- Dose 3
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 21 participants
Where: 1 siteUnited States
Study dates: 30 May 2018to 25 Nov 2018
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, adult, male and/or female (females of non-childbearing potential only), 18 to 55 years of age, inclusive, at screening.
Continuous non-smoker, who has not used nicotine-containing products for at least 3 months prior to dosing, based on subject self-reporting.
Body mass index (BMI) ≥ 18 and < 29 (kg/m2) at screening and weight between 50 and 125 kg (inclusive) at screening.
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms, as deemed by the PI or designee.
A female must be of non childbearing potential and must have undergone one of the following sterilization procedures at least 6 months prior to dosing:
hysteroscopic sterilization;

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bilateral tubal ligation or bilateral salpingectomy;
hysterectomy;
bilateral oophorectomy. or be postmenopausal with amenorrhea for at least 1 year prior to dosing and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.
A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to dosing of study drug. A male who has been vasectomized less than 4 months prior to dosing must follow the same restrictions as a non vasectomized male).
If male, must agree to not donate sperm from dosing until 90 days after dosing.
Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Who cannot join

Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.
Consumes 3 units or more of alcohol per day (e.g., 1 unit is equivalent to 240 mL of wine, 1 bottle of beer [12 oz.], or 1 shot of liquor [1 oz.]).
History or presence of hypersensitivity or idiosyncratic reaction to the study drug and excipients or related compounds.

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History or presence of a disease or disorder, acquired or inherited, that is active, or could be reasonably expected to become active during the study, including but not limited to:
Hypersensitivity to ß-lactam / penicillin derivatives;
Bleeding and blood coagulation disorders, including stroke, hemophilias, thrombophilias, or heparin-induced thrombocytopenia;
Ischemic disorders, including stroke, heart attack, coronary artery disease;
Gastrointestinal disorders, including gastrointestinal bleeds, gallstones, ulcers, diseases or dysfunction of the liver and excluding appendectomy and/or cholecystectomy;
Genitourinary disorders, including renal disease;
Cardiovascular disorders, including aneurysms, vasculitis;
All conditions that are associated with taking medications for pain;
Infection of any organ or system within 30 days of dosing;
Malignant and cancerous neoplasms of any organ or system;
Psychiatric and behavioral disorders;
A clinically significant hematological disorder of any type;
Inflammation and inflammatory diseases of any organ system.
Females of childbearing potential.
Females who are pregnant or who are lactating.
Positive urine drug or alcohol results at screening or check in.
Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
Supine blood pressure is less than 90/50 mmHg or greater than 140/90 mmHg at screening.
Supine heart rate is lower than 40 bpm or higher than 99 bpm at screening.
QTcF interval > 450 msec for males or > 460 msec for females, or history of prolonged QT syndrome at screening.
Estimated creatinine clearance < 90 mL/minutes at screening using the Cockcroft Gault estimation.
Unable to refrain from or anticipates the use of:
Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning approximately 14 days prior to dosing and throughout the study.
Any oral or injectable anticoagulant (e.g., warfarin, heparin, low molecular weight heparin, etc.), coagulants (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and aminomethylbenzoic acid), anti-platelet (e.g., clopidogrel), nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acetylsalicylic acid (ASA) beginning approximately 10 days prior to dosing and throughout the study.
Any drugs known to be significant inducers of cytochrome P-450 enzymes and/or P glycoprotein, including St. John's Wort, for 28 days prior to dosing and throughout the study.
Appropriate sources (e.g., Flockhart TableTM) will be consulted to confirm lack of pharmacokinetic/ pharmacodynamic interaction with study medication. Acetaminophen (up to 2 g per 24 hour period) or any other treatment of an adverse event, drug related or not, and considered appropriate and allowable by the PI or designee may be permitted after dosing.
Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to dosing and throughout the study.
Has participated in strenuous exercise or physical activity within 72 hours prior to Day 1, unless deemed acceptable by the PI or designee.
Donation of blood or significant blood loss within 56 days prior to dosing.
Plasma donation within 7 days prior to dosing.
Has been hospitalized within 2 months of Day -1.
Participation in another clinical study within 30 days prior to dosing. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study.
Surgery within the past 90 days prior to dosing which in the opinion of the PI or designee is clinically relevant.
Presence of any scars, or tattoos which may obscure the injection site, as deemed by PI or designee.
Any condition or circumstance, in the opinion of the PI or designee, which may make the subject unlikely to complete the study or comply with study procedures and requirements, or may pose a risk to the subject's safety.

Trial locations and contacts

1 site in 1 country.

United States1 site

Celerion
Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of E-WE Thrombin as an Intravenous Bolus in Healthy Adult Subjects

The purpose of this study is to assess the safety, tolerability and pharmacodynamics of a single iv dose of E-WE Thrombin in healthy adult subjects.

Conditions: Thrombosis
Being tested: E-WE Thrombin- Dose 1, E-WE Thrombin- Dose 2, E-WE Thrombin- Dose 3, E-WE Thrombin- Dose 4, Placebo
Medical subject headings: Thrombosis

What participants receive

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

E-WE Thrombin- Dose 1Drug
Also called AB002- Dose 1
Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
E-WE Thrombin- Dose 2Drug
Also called AB002- Dose 2
Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.
E-WE Thrombin- Dose 3Drug
Also called AB002- Dose 3
Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.
E-WE Thrombin- Dose 4Drug
Also called AB002- Dose 4
Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.
PlaceboOther
Participants received a single intravenous dose of placebo.

Study groups in NCT03453060
Study group	Role	What they receive
E-WE Thrombin Dose 1	Experimental	Participants will receive a single intravenous dose of 0.5 mcg/kg E-WE Thrombin. Receives: Drug: E-WE Thrombin- Dose 1
E-WE Thrombin Dose 2	Experimental	Participants will receive a single intravenous dose of 1.0 mcg/kg E-WE Thrombin. Receives: Drug: E-WE Thrombin- Dose 2
E-WE Thrombin Dose 3	Experimental	Participants will receive a single intravenous dose of 2.0 mcg/kg E-WE Thrombin. Receives: Drug: E-WE Thrombin- Dose 3
E-WE Thrombin Dose 4	Experimental	Participants will receive a single intravenous dose of 4.0 mcg/kg E-WE Thrombin. Receives: Drug: E-WE Thrombin- Dose 4
Placebo	Placebo comparator	Participants will receive a single intravenous dose of placebo. Receives: Other: Placebo

What is being measured

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

The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.
TEAEs will be determined by symptom driven physical examinations that can include assessment of the skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.
Measured: one month
The Number of Subjects With Clinically Significant Changes in Body Temperature, Frequency, and Relation to Treatment Will be Assessed.
Body temperature will be measured in degrees Celsius. Clinically significant changes in body temperature are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Respiratory Rate, Frequency, and Relation to Treatment Will be Assessed.
Respiratory rate will be measured in breaths per minute. Clinically significant changes in respiratory rate are determined by the PI.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic), Frequency, and Relation to Treatment Will be Assessed.
Systolic and diastolic blood pressure will be measured in mmHg. Clinically significant changes in systolic and diastolic blood pressure are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Heart Rate, Frequency, and Relation to Treatment Will be Assessed.
Heart rate will be measured in beats per minute. Clinically significant changes in heart rate are determined by the PI or designee.
Measured: two days
The Number of Subjects With Abnormal Electrocardiogram and Frequency and/ or Adverse Events That Are Related to Treatment.
12-lead electrocardiogram measurement. Abnormal electrocardiograms are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Activated Partial Thromboplastin Time (aPTT), Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Plasma aPTT will be measured in seconds. Clinically significant changes in aPTT are determined by the PI or designee.
Measured: one month
The Number of Subjects With Clinically Significant Changes in Prothrombin Time, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Prothrombin time will be measured in seconds. Clinically significant changes in prothrombin time are determined by the PI or designee.
Measured: one month
The Number of Subjects With Clinically Significant Changes in Thrombin Time, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Thrombin time will be measured in seconds. Clinically significant changes in thrombin time are determined by the PI or designee.
Measured: one month
The Number of Subjects With Clinically Significant Changes in Plasma Fibrinogen, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Plasma fibrinogen levels will be measured in mg/dL. Clinically significant changes in plasma fibrinogen levels are determined by the PI or designee.
Measured: one month
The Number of Subjects With Injection Site Reaction and/ or Adverse Events That Are Related to Treatment.
Injection site reaction assessment (pain, tenderness, erythema/ redness, and induration/ swelling.
Measured: two days
The Number of Subjects That Develop Treatment-related Immunogenicity.
Immunogenicity measured by plasma anti-drug antibodies.
Measured: one month
The Number of Subjects With Clinically Significant Changes in Blood Urea Nitrogen Levels (BUN) as Part of a Standard Serum Chemistry Panel, Frequency, and Relation to Treatment Will be Assessed.
BUN levels in the blood will be measured in mg/dL. Clinically significant changes in BUN are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Bilirubin (Total and Direct) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Bilirubin (total and direct) levels in the blood will be measured in mg/dL. Clinically significant changes in total and direct bilirubin levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Alkaline Phosphatase Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Alkaline phosphatase levels in the blood will be measured in U/L. Clinically significant changes in alkaline phosphatase levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Aspartate Aminotransferase (AST) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
AST levels in the blood will be measured in U/L. Clinically significant changes in AST levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Alanine Aminotransferase (ALT) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
ALT levels in the blood will be measured in U/L. Clinically significant changes in ALT levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Lactate Dehydrogenase (LDH) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
LDH levels in the blood will be measured in U/L. Clinically significant changes in LDH levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Albumin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Albumin levels in the blood will be measured in g/dL. Clinically significant changes in albumin levels are determined by the PI or designee.
Measured: two days.
The Number of Subjects With Clinically Significant Changes in Sodium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Sodium levels will be measured in mEq/L. Clinically significant changes in sodium levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Potassium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Potassium levels will be measured in mEq/L. Clinically significant changes in potassium levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Chloride Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Chloride levels will be measured in mEq/L. Clinically significant changes in chloride levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Bicarbonate Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Bicarbonate levels will be measured in mEq/L. Clinically significant changes in bicarbonate levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Glucose Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Blood glucose levels will be measured in mg/dL. Clinically significant changes in blood glucose levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Creatinine Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Creatinine levels will be measured in mg/dL. Clinically significant changes in creatinine levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Hemoglobin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Hemoglobin levels will be measured in g/dL. Clinically significant changes in hemoglobin levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Hematocrit Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Hematocrit levels will be measured in %. Clinically significant changes in hematocrit levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Total Leukocyte Counts, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Total leukocyte counts will be measured in 10˄3/uL. Clinically significant changes in leukocyte counts are determined by the PI or designee.
Measured: two days.
The Number of Subjects With Clinically Significant Changes in Differential Leukocyte Counts, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Differential leukocyte counts will be measured in %. Clinically significant changes in differential leukocyte counts are determined by the PI or designee.
Measured: two days.
The Number of Subjects With Clinically Significant Changes in Red Blood Cell Count, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Red blood cell count will be measured in 10˄6/uL. Clinically significant changes in red blood cell counts are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Platelet Count, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Platelet count will be measured in 10˄3/uL. Clinically significant changes in platelet counts are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine pH, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
pH of the urine will be measured. Clinically significant changes in urine pH are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Specific Gravity, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Specific gravity of the urine will be evaluated. Clinically significant changes in specific gravity are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Protein Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Protein levels in the urine will be evaluated. Clinically significant changes in protein levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Glucose Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Glucose levels in the urine will be evaluated. Clinically significant changes in urine glucose are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Ketone Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Ketone levels in the urine will be evaluated. Clinically significant changes in urine ketone levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Bilirubin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Bilirubin levels in the urine will be evaluated. Clinically significant changes in urine bilirubin levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Blood Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Blood levels in the urine will be evaluated. Clinically significant changes in urine blood levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Nitrite Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Nitrite levels in the urine will be evaluated. Clinically significant changes in urine nitrite levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Urobilinogen Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Urobilinogen levels in the urine will be evaluated. Clinically significant changes in urine urobilinogen levels are determined by the PI or designee.
Measured: two days
The Number of Subjects With Clinically Significant Changes in Urine Leukocyte Esterase Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Leukocyte esterase levels in the urine will be evaluated. Clinically significant changes in urine leukocyte esterase levels are determined by the PI or designee.
Measured: two days

Secondary outcomes (1)

The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI).
Plasma APC-PCI levels will be measured in ng/mL.
Measured: Predose, 0.08, 0.25, 0.5, 1, 2, 4, and 24h post-dose

Timeline

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

30 May 201825 Nov 2018

First posted5 Mar 2018
Study start30 May 2018
Primary completion25 Nov 2018
Study completion25 Nov 2018

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 ThrombosisStudies 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: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03453060
Sponsor's protocol ID: EWE-17-01
Status last verified: Oct 2019
First submitted: 20 Feb 2018
Last updated: 29 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Tucker EI, Verbout NG, Markway BD, Wallisch M, Lorentz CU, Hinds MT, Shatzel JJ, Pelc LA, Wood DC, McCarty OJT, Di Cera E, Gruber A. The protein C activator AB002 rapidly interrupts thrombus development in baboons. Blood. 2020 Feb 27;135(9):689-699. doi: 10.1182/blood.2019002771.
PubMed 31977000

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 29 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of E-WE Thrombin as an Intravenous Bolus in Healthy Adult Subjects
ClinicalTrials.gov ID: NCT03453060
Acronym / sponsor ID: EWE-17-01
Conditions: Thrombosis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Aronora, Inc.Industry (pharma, biotech, devices)
Study start: 30 May 2018 (actual)
Primary completion: 25 Nov 2018 (actual)
Study completion: 25 Nov 2018 (actual)
First posted: 5 Mar 2018 (actual)
Results: Posted 29 Oct 2019

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 assess the safety, tolerability and pharmacodynamics of a single iv dose of E-WE Thrombin in healthy adult subjects.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
E-WE Thrombin Dose 1	Experimental	Drug: E-WE Thrombin- Dose 1Participants will receive a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
E-WE Thrombin Dose 2	Experimental	Drug: E-WE Thrombin- Dose 2Participants will receive a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.
E-WE Thrombin Dose 3	Experimental	Drug: E-WE Thrombin- Dose 3Participants will receive a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.
E-WE Thrombin Dose 4	Experimental	Drug: E-WE Thrombin- Dose 4Participants will receive a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.
Placebo	Placebo comparator	Other: PlaceboParticipants will receive a single intravenous dose of placebo.

Who may qualify

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

Key inclusion criteria (12 listed)

Healthy, adult, male and/or female (females of non-childbearing potential only), 18 to 55 years of age, inclusive, at screening.
Continuous non-smoker, who has not used nicotine-containing products for at least 3 months prior to dosing, based on subject self-reporting.
Body mass index (BMI) ≥ 18 and < 29 (kg/m2) at screening and weight between 50 and 125 kg (inclusive) at screening.
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms, as deemed by the PI or designee.
A female must be of non childbearing potential and must have undergone one of the following sterilization procedures at least 6 months prior to dosing:

Key exclusion criteria (41 listed)

Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.
Consumes 3 units or more of alcohol per day (e.g., 1 unit is equivalent to 240 mL of wine, 1 bottle of beer [12 oz.], or 1 shot of liquor [1 oz.]).

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
E-WE Thrombin- Dose 1Also: AB002- Dose 1Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.	Drug	E-WE Thrombin Dose 1
E-WE Thrombin- Dose 2Also: AB002- Dose 2Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	Drug	E-WE Thrombin Dose 2
E-WE Thrombin- Dose 3Also: AB002- Dose 3Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	Drug	E-WE Thrombin Dose 3
E-WE Thrombin- Dose 4Also: AB002- Dose 4Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Drug	E-WE Thrombin Dose 4
PlaceboParticipants received a single intravenous dose of placebo.	Other	Placebo

Primary outcome

The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.
Time frame: one month
TEAEs will be determined by symptom driven physical examinations that can include assessment of the skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.
The Number of Subjects With Clinically Significant Changes in Body Temperature, Frequency, and Relation to Treatment Will be Assessed.
Time frame: two days
Body temperature will be measured in degrees Celsius. Clinically significant changes in body temperature are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Respiratory Rate, Frequency, and Relation to Treatment Will be Assessed.
Time frame: two days
Respiratory rate will be measured in breaths per minute. Clinically significant changes in respiratory rate are determined by the PI.
The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic), Frequency, and Relation to Treatment Will be Assessed.
Time frame: two days
Systolic and diastolic blood pressure will be measured in mmHg. Clinically significant changes in systolic and diastolic blood pressure are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Heart Rate, Frequency, and Relation to Treatment Will be Assessed.
Time frame: two days
Heart rate will be measured in beats per minute. Clinically significant changes in heart rate are determined by the PI or designee.
The Number of Subjects With Abnormal Electrocardiogram and Frequency and/ or Adverse Events That Are Related to Treatment.
Time frame: two days
12-lead electrocardiogram measurement. Abnormal electrocardiograms are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Activated Partial Thromboplastin Time (aPTT), Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Time frame: one month
Plasma aPTT will be measured in seconds. Clinically significant changes in aPTT are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Prothrombin Time, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Time frame: one month
Prothrombin time will be measured in seconds. Clinically significant changes in prothrombin time are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Thrombin Time, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Time frame: one month
Thrombin time will be measured in seconds. Clinically significant changes in thrombin time are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Plasma Fibrinogen, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.
Time frame: one month
Plasma fibrinogen levels will be measured in mg/dL. Clinically significant changes in plasma fibrinogen levels are determined by the PI or designee.
The Number of Subjects With Injection Site Reaction and/ or Adverse Events That Are Related to Treatment.
Time frame: two days
Injection site reaction assessment (pain, tenderness, erythema/ redness, and induration/ swelling.
The Number of Subjects That Develop Treatment-related Immunogenicity.
Time frame: one month
Immunogenicity measured by plasma anti-drug antibodies.
The Number of Subjects With Clinically Significant Changes in Blood Urea Nitrogen Levels (BUN) as Part of a Standard Serum Chemistry Panel, Frequency, and Relation to Treatment Will be Assessed.
Time frame: two days
BUN levels in the blood will be measured in mg/dL. Clinically significant changes in BUN are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Bilirubin (Total and Direct) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Bilirubin (total and direct) levels in the blood will be measured in mg/dL. Clinically significant changes in total and direct bilirubin levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Alkaline Phosphatase Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Alkaline phosphatase levels in the blood will be measured in U/L. Clinically significant changes in alkaline phosphatase levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Aspartate Aminotransferase (AST) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
AST levels in the blood will be measured in U/L. Clinically significant changes in AST levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Alanine Aminotransferase (ALT) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
ALT levels in the blood will be measured in U/L. Clinically significant changes in ALT levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Lactate Dehydrogenase (LDH) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
LDH levels in the blood will be measured in U/L. Clinically significant changes in LDH levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Albumin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days.
Albumin levels in the blood will be measured in g/dL. Clinically significant changes in albumin levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Sodium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Sodium levels will be measured in mEq/L. Clinically significant changes in sodium levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Potassium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Potassium levels will be measured in mEq/L. Clinically significant changes in potassium levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Chloride Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Chloride levels will be measured in mEq/L. Clinically significant changes in chloride levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Bicarbonate Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Bicarbonate levels will be measured in mEq/L. Clinically significant changes in bicarbonate levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Glucose Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Blood glucose levels will be measured in mg/dL. Clinically significant changes in blood glucose levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Creatinine Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.
Time frame: two days
Creatinine levels will be measured in mg/dL. Clinically significant changes in creatinine levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Hemoglobin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Time frame: two days
Hemoglobin levels will be measured in g/dL. Clinically significant changes in hemoglobin levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Hematocrit Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Time frame: two days
Hematocrit levels will be measured in %. Clinically significant changes in hematocrit levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Total Leukocyte Counts, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Time frame: two days.
Total leukocyte counts will be measured in 10˄3/uL. Clinically significant changes in leukocyte counts are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Differential Leukocyte Counts, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Time frame: two days.
Differential leukocyte counts will be measured in %. Clinically significant changes in differential leukocyte counts are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Red Blood Cell Count, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Time frame: two days
Red blood cell count will be measured in 10˄6/uL. Clinically significant changes in red blood cell counts are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Platelet Count, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.
Time frame: two days
Platelet count will be measured in 10˄3/uL. Clinically significant changes in platelet counts are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine pH, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
pH of the urine will be measured. Clinically significant changes in urine pH are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Specific Gravity, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Specific gravity of the urine will be evaluated. Clinically significant changes in specific gravity are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Protein Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Protein levels in the urine will be evaluated. Clinically significant changes in protein levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Glucose Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Glucose levels in the urine will be evaluated. Clinically significant changes in urine glucose are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Ketone Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Ketone levels in the urine will be evaluated. Clinically significant changes in urine ketone levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Bilirubin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Bilirubin levels in the urine will be evaluated. Clinically significant changes in urine bilirubin levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Blood Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Blood levels in the urine will be evaluated. Clinically significant changes in urine blood levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Nitrite Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Nitrite levels in the urine will be evaluated. Clinically significant changes in urine nitrite levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Urobilinogen Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Urobilinogen levels in the urine will be evaluated. Clinically significant changes in urine urobilinogen levels are determined by the PI or designee.
The Number of Subjects With Clinically Significant Changes in Urine Leukocyte Esterase Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.
Time frame: two days
Leukocyte esterase levels in the urine will be evaluated. Clinically significant changes in urine leukocyte esterase levels are determined by the PI or designee.

1 secondary outcome

The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI).
Time frame: Predose, 0.08, 0.25, 0.5, 1, 2, 4, and 24h post-dose

Results and safety

Results posted to the registry on 29 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
E-WE Thrombin Dose 1	4	4
E-WE Thrombin Dose 2	4	4
E-WE Thrombin Dose 3	4	4
E-WE Thrombin Dose 4	4	4
Placebo	5	5

Primary outcome: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.

Time frame: one month. Count of participants. Unit: Participants

Measure	E-WE Thrombin Dose 1 n = 4	E-WE Thrombin Dose 2 n = 4	E-WE Thrombin Dose 3 n = 4	E-WE Thrombin Dose 4 n = 4	Placebo n = 5
Value	0	0	0	3	1

Population analysed: Subjects who received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Primary outcome: The Number of Subjects With Clinically Significant Changes in Body Temperature, Frequency, and Relation to Treatment Will be Assessed.

Time frame: two days. Count of participants. Unit: Participants

Measure	E-WE Thrombin Dose 1 n = 4	E-WE Thrombin Dose 2 n = 4	E-WE Thrombin Dose 3 n = 4	E-WE Thrombin Dose 4 n = 4	Placebo n = 5
Value	0	0	0	0	0

Population analysed: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Primary outcome: The Number of Subjects With Clinically Significant Changes in Respiratory Rate, Frequency, and Relation to Treatment Will be Assessed.

Time frame: two days. Count of participants. Unit: Participants

Measure	E-WE Thrombin Dose 1 n = 4	E-WE Thrombin Dose 2 n = 4	E-WE Thrombin Dose 3 n = 4	E-WE Thrombin Dose 4 n = 4	Placebo n = 5
Value	0	0	0	0	0

Primary outcome: The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic), Frequency, and Relation to Treatment Will be Assessed.

Time frame: two days. Count of participants. Unit: Participants

Measure	E-WE Thrombin Dose 1 n = 4	E-WE Thrombin Dose 2 n = 4	E-WE Thrombin Dose 3 n = 4	E-WE Thrombin Dose 4 n = 4	Placebo n = 5
Value	0	0	0	0	0

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were recorded from subject check-in through follow up which occurred on Day 28.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
E-WE Thrombin Dose 1	0 of 4 (0%)	0 of 4 (0%)	0 of 4
E-WE Thrombin Dose 2	0 of 4 (0%)	0 of 4 (0%)	0 of 4
E-WE Thrombin Dose 3	0 of 4 (0%)	0 of 4 (0%)	0 of 4
E-WE Thrombin Dose 4	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Placebo	0 of 5 (0%)	1 of 5 (20%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31977000Tucker EI, Verbout NG, Markway BD, Wallisch M, Lorentz CU, Hinds MT, Shatzel JJ, Pelc LA, Wood DC, McCarty OJT, Di Cera E, Gruber A. The protein C activator AB002 rapidly interrupts thrombus development in baboons. Blood. 2020 Feb 27;135(9):689-699. doi: 10.1182/blood.2019002771.
Individual participant dataSharing planned: Undecided

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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.

Danielle Armas, MD principal investigator

Celerion

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 E-WE Thrombin- Dose 1, E-WE Thrombin- Dose 2 and E-WE Thrombin- Dose 3 in people with Thrombosis, run by Aronora, Inc. at 1 site in United States.

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 12 inclusion and 41 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 29 Oct 2019. 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 United States. 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 29 Oct 2019). 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?

The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Will be Summarized Using Frequency Counts. (time frame: one month). The study lists 41 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 NCT03453060, 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 29 Oct 2019.