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

NCT02748642 | Completed Phase 1

• 1 other identifier: GB30030
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Atopic Asthma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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)

Study Arms (11)

Part A Cohort A: BITS7201A Dose Level 1 Subcutaneous (SC)

EXPERIMENTAL

Healthy participants will receive a single SC dose of BITS7201A dose Level 1 on Day 1.

Drug: BITS7201A

Part A Cohort B: BITS7201A Dose Level 2 SC

EXPERIMENTAL

Healthy participants will receive a single SC dose of BITS7201A dose Level 2 on Day 1.

Drug: BITS7201A

Part A Cohort C: BITS7201A Dose Level 4 SC

EXPERIMENTAL

Healthy participants will receive a single SC dose of BITS7201A dose Level 4 on Day 1.

Drug: BITS7201A

Part A Cohort D: BITS7201A Dose Level 4 Intravenous (IV)

EXPERIMENTAL

Healthy participants will receive a single IV dose of BITS7201A dose Level 4 on Day 1.

Drug: BITS7201A

Part A Cohort E: BITS7201A Dose Level 6 IV

EXPERIMENTAL

Healthy participants will receive a single IV dose of BITS7201A dose Level 6 on Day 1.

Drug: BITS7201A

Part A: Placebo

PLACEBO COMPARATOR

Healthy participants will receive a single SC or IV dose of placebo matched to BITS7201A on Day 1.

Drug: Placebo

Part B Cohort F: BITS7201A Dose Level 3 SC

EXPERIMENTAL

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

Part B Cohort G: BITS7201A Dose Level 4 SC

EXPERIMENTAL

Healthy participants will receive a single SC dose of BITS7201A dose Level 4 Q4W on Days 1, 29, and 57.

Drug: BITS7201A

Part B Cohort H: BITS7201A Dose Level 5 SC

EXPERIMENTAL

Healthy participants will receive SC dose of BITS7201A dose Level 5 Q4W on Days 1, 29, and 57.

Drug: BITS7201A

Part B Cohort I:BITS7201A Dose Level 5 SC (Mild Atopic Asthma)

EXPERIMENTAL

Mild atopic asthma participants will receive SC dose of BITS7201 dose Level 5 Q4W on Days 1, 29, and 57.

Drug: BITS7201A

Part B: Placebo

PLACEBO COMPARATOR

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

Interventions

BITS7201A DRUG

BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.

Also known as: RO7040547

Part A Cohort A: BITS7201A Dose Level 1 Subcutaneous (SC); Part A Cohort B: BITS7201A Dose Level 2 SC; Part A Cohort C: BITS7201A Dose Level 4 SC; Part A Cohort D: BITS7201A Dose Level 4 Intravenous (IV); Part A Cohort E: BITS7201A Dose Level 6 IV; Part B Cohort F: BITS7201A Dose Level 3 SC; Part B Cohort G: BITS7201A Dose Level 4 SC; Part B Cohort H: BITS7201A Dose Level 5 SC; Part B Cohort I:BITS7201A Dose Level 5 SC (Mild Atopic Asthma)

Placebo DRUG

Placebo matched to BITS72014A will be administered on Day 1 in Part A and on Days 1, 28, and 57 in Part B.

Part A: Placebo; Part B: Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

New Orleans Center for Clinical Research; Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• 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.

  PMID: 30616547 DERIVED

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2016
• First Posted: April 22, 2016
• Study Start: April 7, 2016
• Primary Completion: June 14, 2017
• Study Completion: June 14, 2017
• Last Updated: July 3, 2018

Record last verified: 2018-07

Locations

US (1)