AzTrials
AzTrials

ThrombosisPhase 1NCT03097341

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

A Phase 1 study testing xisomab 3G3- Dose 1, xisomab 3G3-Dose 2 and xisomab 3G3-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
Search all trials

Trial summary

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

Who is it for?
Ages 18 to 48 yearsHealthy volunteers can take part
Conditions the study is for
Thrombosis
What is being tested?
xisomab 3G3- Dose 1, xisomab 3G3-Dose 2 and xisomab 3G3-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
5 Jun 2017to 16 Jan 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 48 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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;
  • A physical barrier method (e.g., male or female condom, contraceptive sponge, diaphragm, cervical cap) with spermicide;
  • An intravaginal system (e.g., NuvaRing®) for at least 3 months prior to dosing;
  • An oral, implantable, transdermal, or injectable hormonal contraceptive for at least 3 months prior to dosing.
  • No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to dosing. 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 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.
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  • 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.
  • Female subjects of childbearing potential.
  • Female subjects who are pregnant or 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).
  • Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
  • Seated heart rate is lower than 40 bpm or higher than 100 bpm at screening.
  • QTcF interval is >450 msec (males) or >460 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
  • Hemoglobin value of less than 11.5 g/dL for females and 13.0 g/dL for males, at screening or check-in.
  • Unable to refrain from or anticipates the use of:
  • Any prescription medications, non-prescription medications, herbal remedies, or vitamin supplements beginning approximately 14 days prior to dosing and throughout the study. Acetaminophen (up to 2 g per 24 hour period) may be permitted during the study and will be documented.
  • Any anticoagulants (i.e., warfarin, Low Molecular Weight Heparin), coagulants, anti-platelet (e.g., clopidogrel), nonsteroidal anti-inflammatory drugs and/or acetylsalicylic acid beginning approximately 28 days prior to dosing and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of pharmacokinetic/pharmacodynamic interaction with study drug.
  • Any investigational drugs or biologics beginning approximately 30 days prior to dosing and throughout the study.
  • Any biologics developed from chinese hamster ovary cell cultures in their life time.
  • Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 28 days prior to dosing and throughout the study.
  • Donation of blood or significant blood loss within 56 days prior to dosing.
  • Plasma donation within 7 days prior to dosing.
  • Strenuous exercise/physical activity which could cause muscle aches or injury, including contact sports at any time from 72 hours before dosing until completion of the study.
  • 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.
  • 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, Pharmacokinetics, and Pharmacodynamics of Xisomab 3G3 in Healthy Adult Subjects

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

Conditions
Thrombosis
Being tested
xisomab 3G3- Dose 1, xisomab 3G3-Dose 2, xisomab 3G3-Dose 3, xisomab 3G3- 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.

  • xisomab 3G3- Dose 1Drug

    Also called AB023- Dose 1

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

  • xisomab 3G3-Dose 2Drug

    Also called AB023- Dose 2

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

  • xisomab 3G3-Dose 3Drug

    Also called AB023- Dose 3

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

  • xisomab 3G3- Dose 4Drug

    Also called AB023- Dose 4

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

  • PlaceboOther

    Participants will receive a single intravenous dose of placebo.

Study groups in NCT03097341
Study groupRoleWhat they receive
xisomab 3G3- Dose 1ExperimentalParticipants will receive a single intravenous dose of 0.1 mg/kg xisomab 3G3.
Receives: Drug: xisomab 3G3- Dose 1
xisomab 3G3- Dose 2ExperimentalParticipants will receive a single intravenous dose of 0.5 mg/kg xisomab 3G3.
Receives: Drug: xisomab 3G3-Dose 2
xisomab 3G3- Dose 3ExperimentalParticipants will receive a single intravenous dose of 2.0 mg/kg xisomab 3G3.
Receives: Drug: xisomab 3G3-Dose 3
xisomab 3G3- Dose 4ExperimentalParticipants will receive a single intravenous dose of 5.0 mg/kg xisomab 3G3.
Receives: Drug: xisomab 3G3- Dose 4
PlaceboPlacebo comparatorParticipants 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.

  1. 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.

    Measured: 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.

  2. 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)

    Measured: 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.

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

    12-lead electrocardiogram measurement

    Measured: 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.

  4. 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)

    Measured: 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.

  5. 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

    Measured: 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.

  6. 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

    Measured: 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)
  1. The Maximum Plasma Concentration (Cmax) of Xisomab 3G3 After a Single Injection Will be Measured in Each Subject.

    Maximum plasma concentration of xisomab 3G3 was estimated based on plasma xisomab 3G3 concentrations. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  2. The Time to Reach Maximum Plasma Concentrations of Xisomab 3G3 (Tmax) After a Single Injection Will be Measured in Each Subject.

    The time to reach maximum plasma concentrations of xisomab 3G3 after a single injection was estimated based on plasma xisomab 3G3 concentrations. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  3. 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.

    The area under the plasma concentration-time curve from time 0 to the last measurable non-zero concentration was estimated based on plasma xisomab 3G3 concentrations. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  4. 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.

    The area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  5. The Percent of AUC0-inf Extrapolated (AUC%Extrap) After a Single Injection of Xisomab 3G3 Will be Calculated for Each Subject.

    The percent of AUC0-inf extrapolated (AUC%extrap) is calculated by (1-AUC0-t/AUC0-inf)*100. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  6. The Apparent First Order Terminal Elimination Rate Constant (Kel) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.

    The apparent first order terminal elimination rate constant will be calculated from a semi-log plot of the plasma concentration versus time curve. The parameter will be calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations). Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  7. The Apparent First Order Terminal Elimination Half-life (T1/2) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.

    The apparent first order terminal elimination half-life will be calculated as 0.693/Kel. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  8. The Apparent Total Plasma Clearance (CL) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.

    The apparent total plasma clearance will be calculated as [Dose/AUC0-inf]. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  9. The Total Apparent Volume of Distribution (Vss) of Xisomab 3G3 After a Single Intravenous Injection Will be Calculated for Each Subject.

    The total apparent volume of distribution (Vss) will be calculated as the mean residence time x clearance. Non-compartmental PK data analysis was performed to estimate the plasma PK parameters of xisomab 3G3.

    Measured: 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).

  10. The Effect of a Single Intravenous Dose of Xisomab 3G3 on the Activated Partial Thromboplastin Time (aPTT) in Healthy Adult Subjects Will be Measured.

    Activated partial thromboplastin time (aPTT) will be used as a surrogate pharmacodynamic marker.

    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)..

Timeline

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

  1. First posted31 Mar 2017
  2. Study start5 Jun 2017
  3. Primary completion16 Jan 2018
  4. Study completion16 Jan 2018

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03097341
Sponsor's protocol ID
3G3-15-01
Status last verified
May 2019
First submitted
21 Mar 2017
Last updated
5 Jun 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: undecided

Publications

  • 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.

    PubMed 30700130

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing xisomab 3G3- Dose 1, xisomab 3G3-Dose 2 and xisomab 3G3-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 21 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 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 20 May 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-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.). The study lists 6 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 NCT03097341, which also lists 1 linked publication.

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

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

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2019.

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