A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Investigate the Pharmacokinetics, Pharmacodynamic Effects, Safety and Tolerability of Repeated Dosing of RO5459072 in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 33
- Primary Endpoint
- Change in concentration of 10-kilodalton (kDa) cluster of differentiation (CD) 74 intermediate (p10) in B-cells
Study Overview
Brief Summary
This randomized, double-blind, placebo-controlled, ascending-dose, parallel-group study will evaluate the pharmacodynamic effects, pharmacokinetics, safety, and tolerability of one week of RG7625 dosing in healthy male and female volunteers. Each participant will receive a single dose of RG7625 or placebo followed by one week of dosing with the same treatment. Each participant will also receive intradermal administration of 4 recall antigens at Screening and on Day 7 of treatment to assess study drug effects on delayed-type hypersensitivity (DTH).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy adult males and females 18 to 60 years of age, inclusive
- •Body mass index 18.0 to 30.0 kilograms per meter-squared (kg/m^2), inclusive
Exclusion Criteria
- •Any clinically relevant abnormalities, concomitant diseases or ongoing medical conditions, abnormal laboratory test results, or a history of any other clinically significant disorders
- •Any major illness within the one month preceding the Screening visit, or any febrile illness within the two weeks preceding the Screening visit
- •Any significant allergic reaction to drugs
- •Immunocompromised or with reduced immune function and/or immunization within 30 days before the first study drug administration or planning vaccination during the study
- •Women who are pregnant or lactating or of childbearing potential
- •Clinically significant abnormal electrocardiogram (ECG) or other risk factors for QT prolongation
- •Use of prescribed or over-the-counter medication
- •Inability or unwillingness to comply with study requirements
Arms & Interventions
Placebo
Healthy volunteers will receive the placebo equivalent to RG7625 as oral capsules once or twice daily for 8 days. Each cohort will receive intradermal administration of 4 antigens (tetanus toxoid, tuberculin purified protein derivative [PPD], Candida albicans, and Trichophyton species) and a negative control at Screening and on Day 7 of treatment to assess for DTH.
Intervention: Placebo (Drug)
RG7625
Participants will undergo a series of Screening visits prior to treatment and 7- to 14-day follow-up. Healthy volunteers will be enrolled in up to 4 cohorts and will receive RG7625 as oral capsules once or twice daily for 8 days. The first cohort is planned to receive 100 milligrams (mg) on Day 1, followed by 100 mg twice daily on Days 3 to 9. Subsequent dose and frequency decisions will be based upon observations in previous cohort(s). Each cohort will receive intradermal administration of 4 antigens (tetanus toxoid, tuberculin PPD, Candida albicans, and Trichophyton species) and a negative control at Screening and on Day 7 of treatment to assess for DTH.
Intervention: RG7625 (Drug)
Outcomes
Primary Outcomes
Change in concentration of 10-kilodalton (kDa) cluster of differentiation (CD) 74 intermediate (p10) in B-cells
Time Frame: From Baseline (Day 1) to 24 hours after the Day 9 dose
Secondary Outcomes
- Incidence of adverse events(Up to 9 weeks)
- Change in size of induration from DTH response(Up to 7 weeks)
- Area under the concentration-time curve (AUC) of RG7625(Pre-dose at Baseline (Day 1) to 24 hours after the Day 9 dose)
- Maximum observed concentration (Cmax) of RG7625(Pre-dose at Baseline (Day 1) to 24 hours after the Day 9 dose)
- Time to maximum observed concentration (Tmax) of RG7625(Pre-dose at Baseline (Day 1) to 24 hours after the Day 9 dose)