Safety and Tolerability Study of Xisomab 3G3 in Healthy Adult Subjects

NCT03097341 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 3G3-15-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of xisomab 3G3 in healthy adult subjects.

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (6)

• The Number of Subjects With Treatment-related Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.

  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.

  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.

• The Number of Subjects With Abnormal Vital Signs That Are Related to Treatment Will be Summarized Using Frequency Counts..

  Vital sign measurements (body temperature, respiratory rate, blood pressure, and heart rate)

  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.

• The Number of Subjects With Abnormal Electrocardiogram That is Related to Treatment Will be Summarized Using Frequency Counts..

  12-lead electrocardiogram measurement

  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.

• The Number of Subjects With Abnormal Injection Site Reaction That Are Related to Treatment Will be Summarized Using Frequency Counts..

  Injection site reaction (pain, tenderness, erythema/ redness, and induration/ swelling)

  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.

• The Number of Subjects With Abnormal Laboratory Values and/ or Adverse Events That Are Related to Treatment Will be Summarized Using Frequency Counts..

  Clinical laboratory tests include serum chemistry, hematology, coagulation parameters (aPTT, PT, and bleeding time), and urinalysis

  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.

• The Number of Subjects That Develop Treatment-related Immunogenicity Will be Summarized Using Frequency Counts.

  Immunogenicity measured by the presence of plasma anti-drug antibodies

  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.

Secondary Outcomes (10)

• 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 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 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).

Study Arms (5)

xisomab 3G3- Dose 1

EXPERIMENTAL

Participants will receive a single intravenous dose of 0.1 mg/kg xisomab 3G3.

Drug: xisomab 3G3- Dose 1

xisomab 3G3- Dose 2

EXPERIMENTAL

Participants will receive a single intravenous dose of 0.5 mg/kg xisomab 3G3.

Drug: xisomab 3G3-Dose 2

xisomab 3G3- Dose 3

EXPERIMENTAL

Participants will receive a single intravenous dose of 2.0 mg/kg xisomab 3G3.

Drug: xisomab 3G3-Dose 3

xisomab 3G3- Dose 4

EXPERIMENTAL

Participants will receive a single intravenous dose of 5.0 mg/kg xisomab 3G3.

Drug: xisomab 3G3- Dose 4

Placebo

PLACEBO COMPARATOR

Participants will receive a single intravenous dose of placebo.

Other: Placebo

Interventions

xisomab 3G3- Dose 1 DRUG

Participants will receive a single intravenous dose of 0.1 mg/kg xisomab 3G3.

Also known as: AB023- Dose 1

xisomab 3G3- Dose 1

xisomab 3G3-Dose 2 DRUG

Participants will receive a single intravenous dose of 0.5 mg/kg xisomab 3G3.

Also known as: AB023- Dose 2

xisomab 3G3- Dose 2

xisomab 3G3-Dose 3 DRUG

Participants will receive a single intravenous dose of 2.0 mg/kg xisomab 3G3.

Also known as: AB023- Dose 3

xisomab 3G3- Dose 3

xisomab 3G3- Dose 4 DRUG

Participants will receive a single intravenous dose of 5.0 mg/kg xisomab 3G3.

Also known as: AB023- Dose 4

xisomab 3G3- Dose 4

Placebo OTHER

Participants will receive a single intravenous dose of placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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 as per PI or designee judgment.
• A non vasectomized male subject whose sexual partner is sterile or was advised to use one of the following during the course of the study (or prior to study as specified) and for 90 days following dosing:
• Abstain from sexual intercourse;
• An intrauterine device with spermicide;

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 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;
• Thromboembolic disease;
• Bleeding in the gastrointestinal tract or central nervous system.
• Allergy to rodents.
• Had a minor surgery or major physical injury less than 4 weeks or major surgery less than 12 weeks prior to screening.
• Was hospitalized within 2 months of dosing, unless deemed acceptable by the PI or designee.

Sponsors & Collaborators

• Aronora, Inc.: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• Lorentz CU, Verbout NG, Wallisch M, Hagen MW, Shatzel JJ, Olson SR, Puy C, Hinds MT, McCarty OJT, Gailani D, Gruber A, Tucker EI. Contact Activation Inhibitor and Factor XI Antibody, AB023, Produces Safe, Dose-Dependent Anticoagulation in a Phase 1 First-In-Human Trial. Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):799-809. doi: 10.1161/ATVBAHA.118.312328.

  PMID: 30700130 DERIVED

MeSH Terms

Conditions

Thrombosis

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Christina U. Lorentz, PhD, Senior Scientist and Project Manager
• Organization: Aronora, Inc.

christina.lorentz@aronorabio.com

503-964-0250

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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 31, 2017
• Study Start: June 5, 2017
• Primary Completion: January 16, 2018
• Study Completion: January 16, 2018
• Last Updated: June 5, 2019
• Results First Posted: May 20, 2019

Record last verified: 2019-05

Locations

US (1)