Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of BOS161721 in Healthy Subjects

NCT03036865 | Completed Phase 1 DMC

• 2 other identifiers: BOS161721-01PXL232187
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Healthy participants; BOS161721; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (13)

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

  up to 52 weeks

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

  up to 52 weeks

• Number of participants with TESAEs of the indicated severity

  up to 52 weeks

• Number of participants with TEAEs of the indicated severity

  up to 52 weeks

• Number of participants with abnormal, clinically significant electrocardiogram findings

  Single-day dosing will occur on Day 1.

  Days -1 and 4 (Residential Period); Days 15, 30, and 90 (Follow-up Period)

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

  Single-day dosing will occur on Day 1.

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

• Number of participants with abnormal, clinically significant hematology parameter values

  Single-day dosing will occur on Day 1.

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

• Number of participants with abnormal, clinically significant clinical chemistry parameter values

  Single-day dosing will occur on Day 1.

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

• Mean total immunoglobulin G (IgG) levels

  Single-day dosing will occur on Day 1.

  Screening; Days -1 and 4 (Residential Period); Days 15, 30, 60, 210 and 270 (Follow-up Period)

• Mean total immunoglobulin M (IgM) levels

  Single-day dosing will occur on Day 1.

  Screening; Days -1 and 4 (Residential Period); Days 15, 30, 60, 210 and 270 (Follow-up Period)

• Mean cluster of differentiation 4 (CD4+) cell count

  Single-day dosing will occur on Day 1.

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

• Number of participants with abnormal, clinically significant physical examination findings

  Single-day dosing will occur on Day 1.

  Screening; Day -1 (Residential Period)

• Number of participants with abnormal, clinically significant targeted physical examination findings

  Single-day dosing will occur on Day 1.

  Day 7 (Residential Period); Days 15, 44, 90, 180, 270, and 360 (Follow-up Period)

Secondary Outcomes (13)

• Mean maximum observed concentration (Cmax) of intravenous (IV) BOS161721

  Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.

• Mean Cmax of subcutaneous (SC) BOS161721

  Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.

• Mean first time to maximum concentration (Tmax) of IV BOS161721

  Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.

• Mean Tmax of SC BOS161721

  Day 1 of Cohorts 2, 3, 4, 5, 7, and 8: predose; following subcutaneous injection on Day 1. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 2, 3, 4, 5, 7, and 8.

• Mean area under the concentration-time curve (AUC) of IV BOS161721

  Day 1 of Cohorts 1 and 6: predose, at the end of infusion/injection (30 minutes); at 0.5, 1, 2, 4, 8, and 12 hours postdose. Postdose on Days 2, 4, 7, 15, 30, 44, 90, 180, 210, 270, and 360 for Cohorts 1 and 6.

Study Arms (15)

Cohort 1: 1 mg, IV BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 1: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching IV placebo.

Drug: Placebo

Cohort 2: 3 mg, SC BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 2: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching SC placebo.

Drug: Placebo

Cohort 3: 10 mg, SC BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 3: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching SC placebo.

Drug: Placebo

Cohort 4: 30 mg, SC BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 4: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching SC placebo.

Drug: Placebo

Cohort 5: 60 mg, SC BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 5: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching SC placebo.

Drug: Placebo

Cohort 6: 22 mg, IV BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 7: 120 mg, SC BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 7: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching SC placebo.

Drug: Placebo

Cohort 8: 240 mg, SC BOS161721

EXPERIMENTAL

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

Drug: BOS161721

Cohort 8: matching placebo

PLACEBO COMPARATOR

Each participant will receive matching SC placebo.

Drug: Placebo

Interventions

BOS161721 DRUG

Single dose administered IV or SC

Cohort 1: 1 mg, IV BOS161721; Cohort 2: 3 mg, SC BOS161721; Cohort 3: 10 mg, SC BOS161721; Cohort 4: 30 mg, SC BOS161721; Cohort 5: 60 mg, SC BOS161721; Cohort 6: 22 mg, IV BOS161721; Cohort 7: 120 mg, SC BOS161721; Cohort 8: 240 mg, SC BOS161721

Placebo DRUG

Single dose administered IV or SC

Cohort 1: matching placebo; Cohort 2: matching placebo; Cohort 3: matching placebo; Cohort 4: matching placebo; Cohort 5: matching placebo; Cohort 7: matching placebo; Cohort 8: matching placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• Boston Pharmaceuticals: lead

Study Sites (1)

Unknown Facility

Baltimore, Maryland, United States

Location

Related Publications (1)

• Hussaini A, Mukherjee R, Berdieva DM, Glogowski C, Mountfield R, Ho PTC. A Double-Blind, Phase I, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BOS161721 in Healthy Subjects. Clin Transl Sci. 2020 Mar;13(2):337-344. doi: 10.1111/cts.12715. Epub 2019 Nov 29.

  PMID: 31664766 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: January 30, 2017
• Study Start: January 1, 2017
• Primary Completion: April 27, 2018
• Study Completion: April 27, 2018
• Last Updated: November 18, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)