Double-Blinded, Placebo-Controlled Phase 1b Study for Safety, PK, Efficacy, PD of RO7049665 in Patients With Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo Controlled Phase Ib Study to Investigate the Safety, Tolerability, Pharmacokinetics, Preliminary Efficacy, and Pharmacodynamics of Subcutaneously Administered RO7049665 in Participants With Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: RO7049665
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Ulcerative Colitis (UC) for at least 12 weeks prior to screening Screening colonoscopy for colorectal cancer conducted within the prior two years if a history of pancolitis with disease duration ≥ 8 years or history of left-sided colitis and disease duration ≥12 years Evidence of disease activity at time of screening Insufficient clinical response to standard of care (SOC) therapy or intolerance to SOC Exclusion Criteria: Diagnosis of Crohn's disease or indeterminate colitis History of infection with hepatitis B, human immunodeficiency virus (HIV), active hepatitis C virus (HCV) infection, or other chronic infection Active infections requiring systemic therapy with antibiotic, antiviral or antifungal or febrile illness within 7 days before Day -1 History of primary or acquired immunodeficiency Abnormal hematologic values Abnormal hepatic enzyme or hepatic function values

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO7049665<br>Participants will receive a subcutaneous (SC) dose of RO7049665 every 2 weeks for 4 doses. | Drug: RO7049665<br>* Multiple ascending doses of RO7049665 will be administered SC.<br>|
| Placebo Comparator: Placebo<br>Participants will receive a SC dose of matching placebo every 2 weeks for 4 doses. | Drug: Placebo<br>* Matching placebo will be administered SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events |  | From baseline up to Day 99 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Concentration (Tmax) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum and the time from SC injection to maximum concentration of RO7049665 will be determined. | From Day 1 to Day 99 | 
| Maximum Serum Concentration Observed (Cmax) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum and the maximum concentration of RO7049665 will be determined. | From Day 1 to Day 99 | 
| AUC from Time 0 to infinity (AUCinf) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum. AUC from time of drug administration extrapolated to infinity (AUCinf) will be determined in a plot of RO7049665 serum concentration versus time. | From Day 1 to Day 99 | 
| AUC from Time 0 to Time tau (AUC0-t) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum. AUC from time of drug administration to time tau (AUC0-t), which is defined as the time of last measurable serum concentration, will be determined in a plot of RO7049665 serum concentration versus time. | From Day 1 to Day 99 | 
| Apparent Clearance (CL/F) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum. Clearance, which is a measure of the rate at which a drug is metabolized or eliminated, will be determined. | From Day 1 to Day 99 | 
| Apparent Volume of Distribution (V/F) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum. Volume of distribution of RO7049665 will be determined. | From Day 1 to Day 99 | 
| Half-life (t1/2) of RO7049665 | Blood samples will be taken pre-dose and at multiple time points after dose administration. RO7049665 concentration will be analyzed in serum. t1/2 is the time required for the serum concentration of RO7049665 to be reduced to half. | From Day 1 to Day 99 | 
| Change from Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) |  | Day 29 and 57 | 
| Change from Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) |  | Day 29 and 57 | 
| Change from Baseline in Histology Score of Sigmoid Colon Biopsies |  | Day 29 and 57 | 
| Change from Baseline in the Mayo Clinic Score (MCS) |  | Day 29 and 57 | 
| Percentage of Participants with Anti-Drug Antibodies | Anti-drug antibody assays will be used to detect anti-drug antibodies against RO7049665. Samples which are positive for anti-drug antibodies will be further assessed using a neutralizing antibody assay. | From Day -1 to Day 99 | 
| Change from Baseline in White Blood Cells |  | Pre-dose and Post-dose from Day 1 to Day 71 |