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

NCT03453060 | Completed Phase 1 Results FDA Drug

• 1 other identifier: EWE-17-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (41)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  two days

• The Number of Subjects That Develop Treatment-related Immunogenicity.

  Immunogenicity measured by plasma anti-drug antibodies.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  Predose, 0.08, 0.25, 0.5, 1, 2, 4, and 24h post-dose

Study Arms (5)

E-WE Thrombin Dose 1

EXPERIMENTAL

Participants will receive a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.

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.

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.

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.

Drug: E-WE Thrombin- Dose 4

Placebo

PLACEBO COMPARATOR

Participants will receive a single intravenous dose of placebo.

Other: Placebo

Interventions

E-WE Thrombin- Dose 1 DRUG

Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.

Also known as: AB002- Dose 1

E-WE Thrombin Dose 1

E-WE Thrombin- Dose 2 DRUG

Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.

Also known as: AB002- Dose 2

E-WE Thrombin Dose 2

E-WE Thrombin- Dose 3 DRUG

Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.

Also known as: AB002- Dose 3

E-WE Thrombin Dose 3

E-WE Thrombin- Dose 4 DRUG

Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.

Also known as: AB002- Dose 4

E-WE Thrombin Dose 4

Placebo OTHER

Participants received a single intravenous dose of placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Aronora, Inc.: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• 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.

  PMID: 31977000 DERIVED

MeSH Terms

Conditions

Thrombosis

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Norah G. Verbout, Senior Scientist and Project Manager
• Organization: Aronora, Inc.

norah.verbout@aronorabio.com

503-964-0250

Study Officials

• Danielle Armas, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: March 5, 2018
• Study Start: May 30, 2018
• Primary Completion: November 25, 2018
• Study Completion: November 25, 2018
• Last Updated: October 29, 2019
• Results First Posted: October 29, 2019

Record last verified: 2019-10

Locations

US (1)