A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Xisomab 3G3 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- xisomab 3G3- Dose 1
- Conditions
- Thrombosis
- Sponsor
- Aronora, Inc.
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- The Number of Subjects With Treatment-related Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of xisomab 3G3 in healthy adult subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adult male and/or female (non-childbearing potential only), 18 to 48 years of age, inclusive, at screening.
- •Continuous non-smoker who has not used nicotine containing products for at least 3 months prior to dosing and throughout the study.
- •Body mass index (BMI) ≥ 19 and ≤ 29.0 (kg/m2) 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 ECGs, as deemed by the PI or designee.
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine must be between the lower limit of normal (LLN; or up to 15% below LLN as not indicative of hepatic or renal disease in healthy subjects) and the upper limit of normal, inclusive, at screening and check-in.
- •aPTT, PT/INR, and platelets, must be within the limits of normal, inclusive, at screening and check-in.
- •Bleeding time must be between 2 to 8 minutes, inclusive, at check-in.
- •For a female of non childbearing potential: must have undergone one of the following sterilization procedures at least 6 months prior to dosing:
- •hysteroscopic sterilization;
- •bilateral tubal ligation or bilateral salpingectomy;
Exclusion Criteria
- •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 drug abuse within the last 2 years prior to dosing.
- •History of alcoholism within the last 2 years prior to dosing or a current history of imbibing 3 or more units of alcohol per day (1 unit is equivalent to 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol).
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drug, any ingredients of the study drug, or related compounds.
- •History of a clinically significant allergy of any kind including a history of allergic or hypersensitivity reactions to any drugs.
- •History or presence of:
- •Bleeding disorder(s) and/or at risk of bleeding, including relevant familial history;
- •Clinically significant anemia, in the opinion of the PI or designee;
Arms & Interventions
xisomab 3G3- Dose 1
Participants will receive a single intravenous dose of 0.1 mg/kg xisomab 3G3.
Intervention: xisomab 3G3- Dose 1
xisomab 3G3- Dose 2
Participants will receive a single intravenous dose of 0.5 mg/kg xisomab 3G3.
Intervention: xisomab 3G3-Dose 2
xisomab 3G3- Dose 3
Participants will receive a single intravenous dose of 2.0 mg/kg xisomab 3G3.
Intervention: xisomab 3G3-Dose 3
xisomab 3G3- Dose 4
Participants will receive a single intravenous dose of 5.0 mg/kg xisomab 3G3.
Intervention: xisomab 3G3- Dose 4
Placebo
Participants will receive a single intravenous dose of placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
The Number of Subjects With Treatment-related Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.
Time Frame: From Subject Check-In through Follow up. Follow up was performed 7 days after Day 29. If the aPTT was not +/- 10% baseline or within normal range, subject was monitored weekly until baseline reached and follow up then occured 7 days after.
TEAEs will be determined by physical examination that will include assessment of 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 Abnormal Vital Signs That Are Related to Treatment Will be Summarized Using Frequency Counts..
Time Frame: From subject Check-In through Follow up. Follow up was performed 7 days after Day 29. If the aPTT was not +/- 10% baseline or within normal range, subject was monitored weekly until baseline reached and follow up then occured 7 days after.
Vital sign measurements (body temperature, respiratory rate, blood pressure, and heart rate)
The Number of Subjects With Abnormal Electrocardiogram That is Related to Treatment Will be Summarized Using Frequency Counts..
Time Frame: From subject Check-In through Follow up. Follow up was performed 7 days after Day 29. If the aPTT was not +/- 10% baseline or within normal range, subject was monitored weekly until baseline reached and follow up then occured 7 days after.
12-lead electrocardiogram measurement
The Number of Subjects With Abnormal Injection Site Reaction That Are Related to Treatment Will be Summarized Using Frequency Counts..
Time Frame: From Study Day 1 through Follow up. Follow up was performed 7 days after Day 29. If the aPTT was not +/- 10% baseline or within normal range, subject was monitored weekly until baseline reached and follow up then occured 7 days after.
Injection site reaction (pain, tenderness, erythema/ redness, and induration/ swelling)
The Number of Subjects With Abnormal Laboratory Values and/ or Adverse Events That Are Related to Treatment Will be Summarized Using Frequency Counts..
Time Frame: From subject Check-In through Follow up. Follow up was performed 7 days after Day 29. If the aPTT was not +/- 10% baseline or within normal range, subject was monitored weekly until baseline reached and follow up then occured 7 days after.
Clinical laboratory tests include serum chemistry, hematology, coagulation parameters (aPTT, PT, and bleeding time), and urinalysis
The Number of Subjects That Develop Treatment-related Immunogenicity Will be Summarized Using Frequency Counts.
Time Frame: From Study Day 1 through Follow up. Follow up was performed 7 days after Day 29. If the aPTT was not +/- 10% baseline or within normal range, subject was monitored weekly until baseline reached and follow up then occured 7 days after.
Immunogenicity measured by the presence of plasma anti-drug antibodies
Secondary Outcomes
- The Maximum Plasma Concentration (Cmax) of Xisomab 3G3 After a Single Injection Will be Measured in Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Time to Reach Maximum Plasma Concentrations of Xisomab 3G3 (Tmax) After a Single Injection Will be Measured in Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Percent of AUC0-inf Extrapolated (AUC%Extrap) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Total Apparent Volume of Distribution (Vss) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Non-zero Concentration (AUC0-t), as Calculated by the Linear Trapezoidal Method, After a Single Injection of Xisomab 3G3 Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Apparent First Order Terminal Elimination Rate Constant (Kel) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Apparent First Order Terminal Elimination Half-life (T1/2) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Apparent Total Plasma Clearance (CL) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.(Pre-dose (0.5h prior to dose), 0.083, 0.25, 0.5, 1,3,8,24,72,120, 168, 216, 336, 504, 672h after dosing as well as follow up (7 days after aPTT returned back to baseline).)
- The Effect of a Single Intravenous Dose of Xisomab 3G3 on the Activated Partial Thromboplastin Time (aPTT) in Healthy Adult Subjects Will be Measured.(Pre-dose (0.5h prior to dose), 1, 24,72, 168, 336, 504, 672h after dosing as well as follow up (7 days after day 29 or after aPTT returned back to baseline)..)