A Study to Investigate the Safety, Pharmacokinetics, and Immunogenicity of BITS7201A in Healthy Volunteers and Participants With Mild Atopic Asthma

A Phase I, Randomized, Observer-Blinded, Placebo-Controlled, Single and Multiple Ascending-Dose Study to Investigate the Safety, Pharmacokinetics, and Immunogenecity of BITS7201A in Healthy Volunteers and Patients With Mild Atopic Asthma

This randomized, observer-blinded, placebo-controlled, single and multiple ascending-dose study will be conducted in two parts to evaluate the safety, pharmacokinetics, and immunogenicity of BITS7201A. Part A will be an ascending, single-dose, sequential-group study where participants will be randomly assigned to active drug or placebo. Part B will be an ascending, multiple-dose, sequential-group study where participants will be randomized to active drug or placebo. Total length of the study is anticipated to be approximately 12 months.

Study Overview

• Status: Completed
• Conditions: Mild Atopic Asthma
• Intervention / Treatment: Drug: BITS7201A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research; Volunteer Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

General Inclusion Criteria:

• Body mass index between 18 and 37 kilograms per meter square (kg/m^2)
• Weight 50-120 kilograms
• Participants in good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs
• Clinical laboratory evaluations should be within the reference range for the test laboratory unless deemed not clinically significant by the Investigator and Sponsor.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method for at least 70 days after the last dose of study drug
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm for at least 70 days after the last dose of study drug

Additional Inclusion Criteria for Participants With Mild Atopic Asthma:

• Diagnosis of asthma for greater than or equal to (>/=) 3 months prior to screening
• History of atopy
• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) >/=60 percent (%) predicted at screening
• Fractional exhaled nitric oxide (FeNO) >/=30 parts per billion (ppb) at screening and at randomization (predose)

Exclusion Criteria:

General Exclusion Criteria:

• History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, gastrointestinal, urologic, neurologic, or psychiatric disorders
• History of hematologic or immunosuppressive disorders
• History of severe depression or suicidal ideation
• History of inflammatory bowel disease
• History of anaphylaxis, hypersensitivity, or significant drug allergies
• History or presence of an abnormal ECG, which is clinically significant
• History of a positive tuberculin skin test in participants who are Bacille Calmette-Guérin (BCG) vaccine naïve or history of a positive interferon-gamma release assay in participants who have received the BCG vaccine
• Participants with neutropenia or thrombocytopenia
• History of alcoholism or drug addiction within 1 year of screening
• Self-reported history of smoking (tobacco, marijuana, or vaping) within the 7 days prior to initiation of study drug
• Smokers not able to pass the tobacco-related laboratory screening and who cannot refrain from smoking during the confinement periods
• Pregnancy or lactation
• History of malignancy, except completely excised basal cell carcinoma or squamous cell carcinoma of the skin
• Any severe bacterial, fungal, or parasitic infections associated with hospitalization or IV antibiotics within 1 year of screening
• History of active parasitic infection within 6 months or exposure to water-born parasites within 6 weeks prior to initiation of study drug
• Upper or lower respiratory tract infection within 4 weeks prior to screening
• Received oral antibiotics within 4 weeks prior to initiation of study drug, or IV/intramuscular (IM) antibiotics within 8 weeks prior to initiation of study drug
• For health volunteers: use of any prescription medications/products within 7 days prior to Day 1 and throughout the study
• Use of any immunosuppressive medication within 30 days or 5 half-lives, whichever is greater, prior to initiation of study drug
• Use of a non-biologic investigational drug or participation in an investigational study with a non-biologic drug within 30 days prior to initiation of study drug (or within 5 half-lives of the investigational product, whichever is greater)
• Use of a biologic investigational therapy or participation in an investigational study involving biologic therapy within 3 months or 5 half-lives, whichever is greater, prior to initiation of study drug
• Received live or attenuated vaccine within 30 days prior to screening
• Received killed vaccine within 14 days prior to initiation of study drug, unless deemed acceptable by the investigator and Sponsor
• Positive blood test for chronic viral infections by: hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody

Additional Exclusion Criteria for Participants With Mild Atopic Asthma:

• Poorly controlled asthma
• Use of any prescription medications and/or products other than asthma and/or allergic rhinitis medications within 7 days prior to Day 1 and throughout the study, unless deemed acceptable by the investigator and Sponsor
• Active lung disease other than asthma
• Occupations with potential exposure to exogenous sources of nitrous oxide and/or associated with elevated FeNO
• Unable to perform FeNO measurement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Cohort A: BITS7201A Dose Level 1 Subcutaneous (SC); Healthy participants will receive a single SC dose of BITS7201A dose Level 1 on Day 1.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part A Cohort B: BITS7201A Dose Level 2 SC; Healthy participants will receive a single SC dose of BITS7201A dose Level 2 on Day 1.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part A Cohort C: BITS7201A Dose Level 4 SC; Healthy participants will receive a single SC dose of BITS7201A dose Level 4 on Day 1.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part A Cohort D: BITS7201A Dose Level 4 Intravenous (IV); Healthy participants will receive a single IV dose of BITS7201A dose Level 4 on Day 1.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part A Cohort E: BITS7201A Dose Level 6 IV; Healthy participants will receive a single IV dose of BITS7201A dose Level 6 on Day 1.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Placebo Comparator: Part A: Placebo; Healthy participants will receive a single SC or IV dose of placebo matched to BITS7201A on Day 1.	Drug: Placebo; Placebo matched to BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.
Experimental: Part B Cohort F: BITS7201A Dose Level 3 SC; Healthy participants will receive a single SC dose of BITS7201A dose Level 3 every 4 weeks (Q4W) on Days 1, 29, and 57.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part B Cohort G: BITS7201A Dose Level 4 SC; Healthy participants will receive a single SC dose of BITS7201A dose Level 4 Q4W on Days 1, 29, and 57.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part B Cohort H: BITS7201A Dose Level 5 SC; Healthy participants will receive SC dose of BITS7201A dose Level 5 Q4W on Days 1, 29, and 57.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Experimental: Part B Cohort I:BITS7201A Dose Level 5 SC (Mild Atopic Asthma); Mild atopic asthma participants will receive SC dose of BITS7201 dose Level 5 Q4W on Days 1, 29, and 57.	Drug: BITS7201A; BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.; Other Names: RO7040547
Placebo Comparator: Part B: Placebo; Healthy participants or mild atopic asthma participants will receive SC doses of placebo matched to BITS7201A Q4W on Days 1, 29, and 57.	Drug: Placebo; Placebo matched to BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	Baseline up to end of the study (Approximately 12 months)
Number of Participants with Anti-Therapeutic Antibodies (ATA) to BITS7201A and Associated Clinical Sequelae	Baseline up to end of the study (Approximately 12 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Serum Concentration (Cmax) of BITS7201A	Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes)
Total Clearance (CL/F) of BITS7201A	Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes)
Apparent Volume of Distribution (Vz/F) of BITS7201A	Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes)
Area under the Concentration-Time Curve (AUC) of BITS7201A	Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes)
Half-Life (t1/2) of BITS7201A	Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes)
Bioavailability (Percentage of Administered Dose Reaching the Systemic Circulation) of BITS7201A	Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes)
Number of Participants with Impact of ATA Status	Baseline up to end of the study (Approximately 12 months)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Staton TL, Peng K, Owen R, Choy DF, Cabanski CR, Fong A, Brunstein F, Alatsis KR, Chen H. A phase I, randomized, observer-blinded, single and multiple ascending-dose study to investigate the safety, pharmacokinetics, and immunogenicity of BITS7201A, a bispecific antibody targeting IL-13 and IL-17, in healthy volunteers. BMC Pulm Med. 2019 Jan 7;19(1):5. doi: 10.1186/s12890-018-0763-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2016
• Primary Completion (Actual): June 14, 2017
• Study Completion (Actual): June 14, 2017

Study Registration Dates

• First Submitted: April 6, 2016
• First Submitted That Met QC Criteria: April 19, 2016
• First Posted (Estimate): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): July 3, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: GB30030