Clinical trial NCT05098080: Hutrukin to Analyze Safety and PK in Healthy Volunteers
Official title: 2021-PT054: A Randomized Phase I Open-Label, Placebo-Controlled, Dose Escalation Study to Evaluate Safety and Pharmacokinetics of Hutrukin Via Intravenous Administration in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Lead sponsor: XBiotech, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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).

Detailed description: Study Title: A Randomized Phase I Open-Label, Placebo-Controlled, Dose Escalation Study to Evaluate Safety and Pharmacokinetics of Hutrukin via Intravenous Administration in Healthy Subjects

Sponsor: XBiotech USA, Inc.

Study Chair: Neha Reshamwala, MD

Number of Planned Subjects: 24 healthy subjects with 8 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 Hutrukin and then evaluation over 28 days. Blood will be sampled at various time points for blood chemistry, hematological assessment and Hutrukin serum/plasma concentrations. Safety and tolerability will be evaluated.

Eligibility criteria: Inclusion Criteria:

1. Age: ≥18 and weight ≥40 kg.
2. 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
3. Adequate renal function, defined by serum creatinine ≤ 1.5 x lab ULN.
4. 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
5. 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.
6. 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.
7. Signed and dated Institutional Review Board (IRB) approved informed consent before any protocol-specific screening procedures are performed.

Exclusion Criteria:

1. Treatment with any biologicals (including intravenous immunoglobulin) or investigational agents within the last 4 weeks (or 5 half-lives, whichever is longer).
2. 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).
3. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
4. Treatment with immunosuppressant agents, including corticosteroids or cyclosporine within the last 4 weeks.
5. 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.
6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
7. Abnormal ECG with any clinically significant findings or with QTc \>470 ms.
8. 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.
9. Infectious disease:

   • Positive HIV, RPR, Hepatitis B or C, TB (QuantiFERON-TB Gold (QFT)/ IGRA)
10. History of immunodeficiency.
11. Female subjects who are pregnant, planning to become pregnant during the course of the study, or breast-feeding.
12. Major surgery within 28 days prior to Day 0.
13. History of progressive multifocal leukoencephalopathy (PML) or other demyelinating disease.
14. History of malignancy before screening with the exception of squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix.

Primary outcomes:
measure: 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.
timeFrame: 28 days
Secondary outcomes:
measure: Maximum plasma concentration of test article
timeFrame: 28 days
measure: Plasma concentration at various time points including terminal concentration
timeFrame: 28 days
measure: Half-life
timeFrame: 28 days
measure: Total exposure
timeFrame: 28 days
Other outcomes:
Locations:
city: Austin
country: United States
facility: BioBehavioral Research of Austin, A Telemed2U Company
state: Texas
Study officials:
affiliation: BioBehavioral Research of Austin
name: Neha Reshamwala, MD
role: PRINCIPAL_INVESTIGATOR
References: