Clinical trial NCT03943550: Double-Blinded, Placebo-Controlled Phase 1b Study for Safety, PK, Efficacy, PD of RO7049665 in Participants With Ulcerative Colitis (UC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-05-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From baseline up to safety follow-up visit on Day 99
Secondary outcomes:
measure: Time to Maximum Concentration (Tmax) of RO7049665
timeFrame: Day 1 to Day 15 (predose) and Day 43 (post-dose)
measure: Maximum Serum Concentration Observed (Cmax) of RO7049665
timeFrame: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
measure: Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665
timeFrame: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
measure: Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES)
timeFrame: Baseline, Days 29 and 57
measure: Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
timeFrame: Baseline, Days 29 and 57
measure: Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS)
timeFrame: Baseline, Days 29 and 57
measure: Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI)
timeFrame: Baseline, Days 29 and 57
measure: Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI)
timeFrame: Baseline, Days 29 and 57
measure: Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response
timeFrame: Baseline, Days 29 and 57
measure: Number of Participants With Anti-Drug Antibodies (ADAs)
timeFrame: Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43
measure: Change From Baseline in White Blood Cells (Tregs, Teffs)
timeFrame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
measure: Change From Baseline in White Blood Cells (Natural Killer (NK) Cells)
timeFrame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
measure: Change From Baseline in White Blood Cells (B Cells)
timeFrame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
measure: Change From Baseline in Eosinophils
timeFrame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 8, 22, 36, 57, 71 and follow-up visit on Day 99
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Tbilisi
country: Georgia
facility: The Research Institute of Clinical Medicine
city: Balatonfüred
country: Hungary
facility: Drug Research Centre Gyogyszervizsgalo Kozpontot Kft.
city: Budapest
country: Hungary
facility: SE ÁOK I. sz. Belgyógyászati Klinika
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Phase 1 Unit- Spitalul Clinic Republican Location
city: Kapitanovka Village
country: Ukraine
facility: Medical center of Yuriy Spizhenko LLC
state: KIEV Governorate
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: