临床试验/NCT03036865

NCT03036865已完成1 期

A Double-blind, Phase 1, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of BOS161721 in Healthy Subjects

Boston Pharmaceuticals0 个研究点目标入组 61 人开始时间: 2017年1月最近更新: 2020年11月18日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Boston Pharmaceuticals
入组人数: 61
主要终点: Number of participants with any treatment-emergent non-serious adverse event (TEAE)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

Study BOS161721-01 is a randomized, single center, double-blind, placebo-controlled trial conducted to study the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending intravenous (IV) and subcutaneous (SC) doses of BOS161721 or placebo in healthy adult male and female participants.

详细描述

Study BOS161721-01 will consist of 7 single ascending dose (SAD) cohorts, each with 8 participants (6 active:2 placebo), and an eighth SAD cohort with 5 participants (all active). Participants will be randomized in a 3:1 ratio (BOS161721:placebo) and will either receive a single dose of BOS161721 (1, 3, 10, 22, 30, 60, 120, or 240 milligrams [mg]) or placebo. Participants in Cohort 1 will receive the lowest dose, administered IV (1 mg), followed by Cohort 2, in which participants will receive the second lowest dose, administered SC (3 mg). BOS161721 or placebo will also be administered SC in Cohorts 3, 4, 5, 7, and 8. Participants in Cohort 6 will be administered an IV dose of 22 mg (5 active) in parallel to the 60 mg SC-dosed fifth cohort. This dose has been selected to generate a similar exposure to that following the 30 mg SC dose. The actual Cohort 6 IV dose may be adjusted upon available PK data.

Participants will be in this study for up to 56 weeks, which includes a Screening Period of up to 28 days, a single-dose treatment day (during the in-subject treatment period), and a 52-week post-treatment Follow-up Period, which is required due to the potential half-life of BOS161721.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Basic Science
盲法: Triple (Participant, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Participant voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)-approved informed consent prior to performing any of the Screening procedures
•Participants should be between 18 and 55 years (both inclusive) of age at the time of Screening, with a body mass index (BMI) between 17.5 and 32 kilograms per meters squared (kg/m^2) (both inclusive) at the time of Screening, have a weight > 50 kg and < 120 kg at the time of Screening, and be in general good health at least 8 weeks prior to the Screening visit. Good health is defined as individuals without known disease(s) as determined by a responsible physician, based on medical evaluation, including medical history, physical examination, laboratory tests, imaging, and cardiac monitoring.
•Women of non-childbearing potential status:
•Hysterectomy;
•Bilateral tubal ligation/tubal occlusion;
•Bilateral salpingectomy;
•Bilateral oophorectomy;
•Postmenopausal - defined as 12 months of spontaneous amenorrhea (In questionable cases, a blood sample will be taken with simultaneous testing of follicle-stimulating hormone (FSH) and estradiol levels, which should be consistent with menopausal range.)
•Women of childbearing potential will be allowed to participate and have to agree to use at least 1 of the following contraception methods at all times throughout study participation in addition to either a condom with spermicide or a diaphragm/cervical cap with spermicide:
•Non-hormonal intrauterine device (IUD; Paragard®/copper)
•Hormonal IUD (Mirena®)
•Nexplanon® or implantation - progesterone inserts under the skin
•Males will either be sterile, agree to be abstinent from Day -1 through the last study visit, or agree to use 2 highly effective methods of contraception such as:
•A male condom with spermicide;
•A sterile sexual partner;
•Use by female sexual partner of an IUD with spermicide; a female condom with spermicide; contraceptive sponge with spermicide; an intravaginal system; a diaphragm with spermicide; a cervical cap with spermicide; or oral, implantable, transdermal, or injectable contraceptive(s).
•Non-smokers or people who smoke up to 5 cigarettes per day but less than 10 packs per year
•Participants should be willing and able to comply with all study procedures. The criterion for inclusion will be reviewed and verified at Screening and admission.

排除标准

•Prior clinical trial experience with monoclonal antibodies if there were clinically relevant tolerability issues with previous administration or if a washout period of 60 days or 5 half-lives (whichever is longer) has not occurred prior to the planned first day of dosing
•History of any autoimmune disease (e.g., rheumatoid arthritis, Lupus)
•History or current diagnosis of cancer, with the exception of non-melanoma skin cancer or cervical cancer in situ treated with apparent success with curative therapy (response duration > 5 years)
•Asthma, currently treated with or in the opinion of the Principal Investigator likely to require additional systemic glucocorticosteroid therapy during the study, is exclusionary.
•History of any clinically important drug or vaccine allergy or anaphylaxis
•A cluster of differentiation 4 (CD4+) lymphocyte count < 500 cell/millimeters cubed (mm^3) at Screening
•Positive anti-keyhole limpet hemocyanin (KLH) antibodies at Screening
•Previous immunization with KLH
•Known allergy to shellfish, KLH vaccine, or hypersensitivity to proteins foreign to the body
•Levels of Immunoglobulin G (IgG) and Immunoglobulin M (IgM) outside of reference value deemed clinically significant by the Principal Investigator at Screening
•History or sensitivity to heparin or heparin-induced thrombocytopenia
•Participants with cryptosporidium in the stool sample at Screening
•Abnormal bilirubin or alanine aminotransferase (ALT) at Screening as judged by the Principal Investigator to be clinically significant
•Positive urine drug screen at Screening or Day -1
•History of alcohol dependence as determined by a positive alcohol serum test at Screening or Day -1 or participants who consume more than 14 (female participants) or 21 (male participants) units of alcohol a week (unit = 1 glass of wine [125 milliliters (mL)/4 ounces] = 1 measure [25 mL/1 ounce] of spirits = 284 mL [10 ounces] of beer)
•Participants who have a positive test, or have been treated, for Hepatitis A, Hepatitis B, Hepatitis C virus, human immunodeficiency virus (HIV), cytomegalovirus (CMV) or Epstein-Barr virus (EBV). Regarding Hepatitis B, any of the following would exclude the participant from the study:
•Participants with positive Hepatitis B Surface antigen (HBsAg);
•Participants with Hepatitis B DNA levels > 200 copies/mL (quantified by real-time polymerase chain reaction) in case the participant is positive for Hepatitis B surface antibody (HBsAb) but negative for HBsAg;
•Positive for Hepatitis B core antibody (HBcAb)
•Current clinical, radiographic, or laboratory evidence of active tuberculosis (TB)
•A history of active TB within the last 3 years before Screening, even if treated
•Therapy for latent TB that has not been completed as per local country guidelines
•Positive interferon gamma release assay (IGRA) for TB unless proper treatment is documented, as described above
•Donation of blood (> 500 mL) or blood products within 2 months (56 days) prior to Day -1
•Any medically relevant pre-existing condition that could jeopardize the safety of the participant during the trial
•Any participant, on the judgment of the Principal Investigator, who would be considered unsuitable for the clinical trial
•A shingles infection in the last 6 months prior to Screening
•Live vaccination or use of steroids in the last 2 months prior to Screening
•Use of prescription medications (except for oral contraceptive) and over-the-counter treatments, including herbal supplements such as St. John's Wart (except multivitamins), in the 2 weeks prior to Screening
•Participants with poor dental health and/or severe foot fungal infections, as judged by the Principal Investigator

研究组 & 干预措施

Cohort 3: matching placebo

Placebo Comparator

Each participant will receive matching SC placebo.

干预措施: Placebo (Drug)

Cohort 1: matching placebo

Placebo Comparator

Each participant will receive matching IV placebo.

干预措施: Placebo (Drug)

Cohort 3: 10 mg, SC BOS161721

Experimental

Each participant will receive a single SC dose of BOS161721 10 mg.

干预措施: BOS161721 (Drug)

Cohort 2: 3 mg, SC BOS161721

Experimental

Each participant will receive a single subcutaneous (SC) dose of BOS161721 3 mg.

干预措施: BOS161721 (Drug)

Cohort 2: matching placebo

Placebo Comparator

Each participant will receive matching SC placebo.

干预措施: Placebo (Drug)

Cohort 1: 1 mg, IV BOS161721

Experimental

Each participant will receive a single intravenous (IV) dose of BOS161721 1 milligram (mg).

干预措施: BOS161721 (Drug)

Cohort 4: 30 mg, SC BOS161721

Experimental

Each participant will receive a single SC dose of BOS161721 30 mg.

干预措施: BOS161721 (Drug)

Cohort 4: matching placebo

Placebo Comparator

Each participant will receive matching SC placebo.

干预措施: Placebo (Drug)

Cohort 5: 60 mg, SC BOS161721

Experimental

Each participant will receive a single SC dose of BOS161721 60 mg.

干预措施: BOS161721 (Drug)

Cohort 5: matching placebo

Placebo Comparator

Each participant will receive matching SC placebo.

干预措施: Placebo (Drug)

Cohort 6: 22 mg, IV BOS161721

Experimental

Each participant will receive a single IV dose of BOS161721 22 mg.

干预措施: BOS161721 (Drug)

Cohort 7: 120 mg, SC BOS161721

Experimental

Each participant will receive a single SC dose of BOS161721 120 mg.

干预措施: BOS161721 (Drug)

Cohort 7: matching placebo

Placebo Comparator

Each participant will receive matching SC placebo.

干预措施: Placebo (Drug)

Cohort 8: 240 mg, SC BOS161721

Experimental

Each participant will receive a single SC dose of BOS161721 240 mg.

干预措施: BOS161721 (Drug)

Cohort 8: matching placebo

Placebo Comparator

Each participant will receive matching SC placebo.

干预措施: Placebo (Drug)

结局指标

主要结局

Number of participants with any treatment-emergent non-serious adverse event (TEAE)

时间窗: up to 52 weeks

Number of participants with any treatment-emergent serious adverse event (TESAE)

时间窗: up to 52 weeks

Number of participants with TEAEs of the indicated severity

时间窗: up to 52 weeks

Number of participants with abnormal, clinically significant vital sign (blood pressure, heart rate, temperature) values

时间窗: Screening; Days -1, 1, 2, 4, and 7 (Residential Period); Days 15, 30, 44, 60, 90, 180, 210, 270, and 360 (Follow-up Period)