Hutrukin Safety PK Study
Study Details
Study Description
Brief Summary
The study will be a Phase I, open label, safety and pharmacokinetics study of HutrukinTM in at least three healthy subjects in each of the three dose cohorts (1,000 mg, 3,000 mg and 5,000 mg).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Study Title: A Phase I Open Label, Dose Escalation Study to Evaluate Safety and Pharmacokinetics of HutrukinTM in Healthy Subjects
Sponsor: XBiotech USA, Inc.
Study Chair: Neha Reshamwala, MD
Number of Planned Subjects: Nine healthy subjects with three subjects in each of the dose cohorts of HutrukinTM.
Approximate Duration:
Approximately 38 days which includes a screening period of up to 10 days followed by one intravenous push of HutrukinTM and then blood sampled at various time points for blood chemistry, hematological assessment and HutrukinTM serum/plasma concentrations over 28 days. Safety and tolerability will be evaluated.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HutrukinTM At least three healthy subjects in each of the three dose cohorts (1000 mg, 3000 mg, and 5000 mg), three subjects will be administered HutrukinTM. |
Biological: HutrukinTM
HutrukinTM that binds the human cytokine IL-1α with high affinity and is an effective blocker of IL-1α biological activity. HutrukinTM is a True Human™ therapeutic antibody. That is, the antibody was generated by a natural human immune response and was cloned directly from a human peripheral B lymphocyte. No in vitro affinity maturation or modifications have been made to improve its natural binding affinity. A true human antibody should be effectively non-immunogenic in humans and thus exhibit optimal activity and pharmacokinetics indistinguishable from native IgG1 immunoglobulin.
|
Outcome Measures
Primary Outcome Measures
- Number of subjects with treatment related adverse events assessed according to CTCAE v5.0 of one single intravenous dose of HutrukinTM in healthy subjects at each dose level. [28 days]
Participants will be monitored for acute reactions, blood chemistry and hematology immediately after dosing and at multiple time points up to 28 days. All adverse events will be documented at multiple time points and assessed in terms those possibly, probably and definitely related to test article according to CTCAE v5.0 criteria. Anti-drug antibodies (ADA) will also be evaluated.
Secondary Outcome Measures
- Maximum plasma concentration of test article [28 days]
The maximum plasma concentration will be assessed using a proprietary immunoassay to detect circulating HutrukinTM.
- Plasma concentration at various time points including terminal concentration [28 days]
Terminal plasma concentration will be assessed at 28 days.
- Half-life [28 days]
Half-life will be assessed.
- Total exposure [28 days]
Area under the curve will be determined based on measured plasma levels over 28 days.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age: ≥18
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Adequate bone marrow function defined as:
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absolute neutrophil count (neutrophil and bands) of ≥ 1,500/mm3 (≥ 1.5 x 109/L)
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platelet count > 150,000/mm3
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hemoglobin of ≥ 10 g/dL
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Adequate renal function, defined by serum creatinine ≤ 1.5 x lab ULN.
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Adequate hepatic function defined as:
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serum albumin ≥ 3.0 g/dL
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total bilirubin ≤ 1.5 times lab ULN.
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alanine aminotransferase (ALT) ≤ 2.0 times lab ULN.
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aspartate aminotransferase (AST) ≤ 2.0 times lab ULN
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For female subjects of childbearing potential WOCBP, a negative pregnancy test at screening and the female subjects must agree to either abstain from sexual intercourse or use reliable, effective contraception such as hormonal contraceptive, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, or use of a condom by their partner. Women of non-childbearing potential include those who cannot get pregnant medically, including post-menopausal women and those with a history of hysterectomy or surgical sterilization.
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Male participants must agree to abstain from sexual intercourse or use a reliable, effective contraceptive method, such as condoms, or have had a vasectomy. Alternatively, female partners of male subjects enrolled in the study must use reliable, effective contraception such as hormonal contraceptive, intrauterine device (IUD), diaphragm with spermicide, or contraceptive sponge.
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Signed and dated Institutional Review Board (IRB) approved informed consent before any protocol-specific screening procedures are performed.
Exclusion Criteria:
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Treatment with any biologicals (including intravenous immunoglobulin) or investigational agents within the last 4 weeks (or 5 half-lives, whichever is longer).
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Uncontrolled or significant cardiovascular disease, including:
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A myocardial infarction within the past 6 months.
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Uncontrolled angina within the past 3 months.
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Congestive heart failure within the past 3 months, defined as New York Heart Association (NYHA) Class II or higher.
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Uncontrolled hypertension (blood pressure >160 mm Hg systolic or >100 mm Hg diastolic).
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Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
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Treatment with immunosuppressant agents, including corticosteroids or cyclosporine within the last 4 weeks.
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Serious uncontrolled medical disorders, such as uncontrolled diabetes, active peptic ulcer disease, cerebrovascular accident within three months, ongoing congestive heart failure, and any other condition, which in the opinion of the investigator, would put the subject at risk by participating in the trial.
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History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
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Abnormal ECG with any clinically significant findings or with QTc >470 ms.
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Infection requiring treatment with antibiotics within 3 weeks prior to screening.
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Infectious disease:
• Positive HIV, RPR, Hepatitis B or C, TB (QuantiFERON-TB Gold (QFT)/ IGRA)
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History of immunodeficiency.
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Female subjects who are pregnant, planning to become pregnant during the course of the study, or breast-feeding.
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Major surgery within 28 days prior to Day 0.
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History of progressive multifocal leukoencephalopathy (PML) or other demyelinating disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | BioBehavioral Research of Austin, A Telemed2U Company | Austin | Texas | United States | 78759 |
Sponsors and Collaborators
- XBiotech, Inc.
Investigators
- Principal Investigator: Neha Reshamwala, MD, BioBehavioral Research of Austin
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-PT054