A Multiple Ascending-Dose Study of RG7625 in Healthy Volunteers

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).

Official Title
-----------------
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

Conditions
-----------------
Healthy Volunteer

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: RG7625


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Participants will receive the placebo equivalent to RG7625 once or twice daily for 8 days. The first dose will be administered on Day 1 and the regimen will be continued during Days 3 to 9, with only a single dose given on Day 9.<br>|
| Experimental: RG7625<br>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. | Drug: RG7625<br>* Participants will receive RG7625 as oral capsules once or twice daily for 8 days. The first dose will be administered on Day 1 and the regimen will be continued during Days 3 to 9, with only a single dose given on Day 9.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of 10-kilodalton (kDa) cluster of differentiation (CD) 74 intermediate (p10) in B-cells |  | From Baseline (Day 1) to 24 hours after the Day 9 dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |