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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 45
- Locations
- 6
- Primary Endpoint
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Study Overview
Brief Summary
The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosed with 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
Arms & Interventions
RO7049665
Participants will receive a subcutaneous (SC) dose of RO7049665 every 2 weeks for 4 doses.
Intervention: RO7049665 (Drug)
Placebo
Participants will receive a SC dose of matching placebo every 2 weeks for 4 doses.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From baseline up to safety follow-up visit on Day 99
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. Severity of AEs were graded according to NCI CTCAE v4.0.
Secondary Outcomes
- Maximum Serum Concentration Observed (Cmax) of RO7049665(Days 1 and 43: Pre-dose, 6 h and 12 h post-dose)
- Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665(Days 1 and 43: Pre-dose, 6 h and 12 h post-dose)
- Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES)(Baseline, Days 29 and 57)
- Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS)(Baseline, Days 29 and 57)
- Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI)(Baseline, Days 29 and 57)
- Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI)(Baseline, Days 29 and 57)
- Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response(Baseline, Days 29 and 57)
- Time to Maximum Concentration (Tmax) of RO7049665(Day 1 to Day 15 (predose) and Day 43 (post-dose))
- Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)(Baseline, Days 29 and 57)
- Change From Baseline in White Blood Cells (Tregs, Teffs)(Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71)
- Change From Baseline in White Blood Cells (B Cells)(Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71)
- Number of Participants With Anti-Drug Antibodies (ADAs)(Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43)
- Change From Baseline in White Blood Cells (Natural Killer (NK) Cells)(Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71)
- Change From Baseline in Eosinophils(Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 8, 22, 36, 57, 71 and follow-up visit on Day 99)