Hutrukin to Analyze Safety and PK in Healthy Volunteers

NCT05098080 | Completed Phase 1 FDA Drug

• 1 other identifier: 2021-PT054
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be a Phase I, open label, safety and pharmacokinetics study of HutrukinTM in at least eight healthy subjects in each of the three dose cohorts (1,000 mg, 3,000 mg and 5,000 mg).

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  28 days

Secondary Outcomes (4)

• Maximum plasma concentration of test article

  28 days

• Plasma concentration at various time points including terminal concentration

  28 days

• Half-life

  28 days

• Total exposure

  28 days

Study Arms (2)

Hutrukin

ACTIVE COMPARATOR

At least six healthy subjects in each of the three dose cohorts (1000 mg, 3000 mg, and 5000 mg), will be administered Hutrukin.

Biological: Hutrukin

Placebo

PLACEBO COMPARATOR

At least two healthy subjects in each of the three dose cohorts (1000 mg, 3000 mg, and 5000 mg), will be administered placebo.

Biological: Placebo

Interventions

Hutrukin BIOLOGICAL

Hutrukin that binds the human cytokine IL-1α with high affinity and is an effective blocker of IL-1α biological activity. Hutrukin 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.

Hutrukin

Placebo BIOLOGICAL

Placebo control for Hutrukin IV push.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥18 and weight ≥40 kg.
• Adequate bone marrow function defined as:
• absolute neutrophil count (neutrophil and bands) of ≥ 1,500/mm3 (≥ 1.5 x 109/L)
• platelet count \> 150,000/mm3
• hemoglobin of ≥ 10 g/dL
• Adequate renal function, defined by serum creatinine ≤ 1.5 x lab ULN.
• Adequate hepatic function defined as:
• serum albumin ≥ 3.0 g/dL
• total bilirubin ≤ 1.5 times lab ULN.
• alanine aminotransferase (ALT) ≤ 2.0 times lab ULN.
• aspartate aminotransferase (AST) ≤ 2.0 times lab ULN
• 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.
• 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.
• Signed and dated Institutional Review Board (IRB) approved informed consent before any protocol-specific screening procedures are performed.

You may not qualify if:

• Treatment with any biologicals (including intravenous immunoglobulin) or investigational agents within the last 4 weeks (or 5 half-lives, whichever is longer).
• Uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within the past 6 months.
• Uncontrolled angina within the past 3 months.
• Congestive heart failure within the past 3 months, defined as New York Heart Association (NYHA) Class II or higher.
• Uncontrolled hypertension (blood pressure \>160 mm Hg systolic or \>100 mm Hg diastolic).
• Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
• Treatment with immunosuppressant agents, including corticosteroids or cyclosporine within the last 4 weeks.
• History of any clinically significant medical disorders the investigator decides should exclude the participant, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Abnormal ECG with any clinically significant findings or with QTc \>470 ms.
• Serious infection (example: sepsis, pneumonia, or pyelonephritis), or have been hospitalized or received intravenous (IV) antibiotics for a serious infection during the 3 months prior to the screening visit.
• Infectious disease:
• Positive HIV, RPR, Hepatitis B or C, TB (QuantiFERON-TB Gold (QFT)/ IGRA)
• History of immunodeficiency.

Sponsors & Collaborators

• XBiotech, Inc.: lead

Study Sites (1)

BioBehavioral Research of Austin, A Telemed2U Company

Austin, Texas, 78759, United States

Location

Study Officials

• Neha Reshamwala, MD

  BioBehavioral Research of Austin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eight healthy subjects will be in each of the three dose cohorts (1,000 mg, 3,000 mg and 5,000 mg). For each dose cohort, six subjects will be administered Hutrukin and two will be administered placebo and the study will not proceed to the next dose level unless the tested dose level has been deemed to have acceptable tolerability and safety. Subjects will undergo blood sampling at multiple time points up to 28 days. Subjects will also be evaluated for the development of anti-drug antibodies (ADA). Dose escalation will utilize a 6+2 design with sentinel dosing and doses will be explored in cohort of 8 subjects (6 active drug and 2 placebo). There are two sub-groups, the first is comprised of one subject receiving Hutrukin and one subject receiving placebo, the second sub-group is comprised of five subjects receiving active drug and one subject receiving placebo. A 24-hour observation window will be given before enrolling the subjects in the second sub-group.

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: October 28, 2021
• Study Start: April 10, 2023
• Primary Completion: October 24, 2023
• Study Completion: April 5, 2024
• Last Updated: July 23, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)