Ulcerative Colitis
Conditions
Brief summary
The principal aim of this study is to evaluate the safety and tolerability of RO7049665 in participants with active ulcerative colitis (UC).
Interventions
DRUGRO7049665
Multiple ascending doses of RO7049665 will be administered SC.
DRUGPlacebo
Matching placebo will be administered SC.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy (i.e., centrally read MCS-ES) and Physician Global Assessment (PGA). Flexible sigmoidoscopy (or colonoscopy) was centrally read and scored using the MCS-ES scoring systems. The disease was considered as endoscopic normal or inactive if the MCS-ES (centrally read) was 0, mild (erythema, decreased vascular pattern) if MCS-ES was 1, moderate (marked erythema, absent vascular pattern, erosions) if MCS-ES was 2 and severe (spontaneous bleeding, ulceration) if MCS-ES was 3. The Endoscopy Subscore of the Mayo Score was modified so that a value of 1 did not include friability. A negative change from baseline indicates improvement. |
| Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Baseline, Days 29 and 57 | Flexible sigmoidoscopy (or colonoscopy) were centrally read and scored using the UCEIS scoring systems. The UCEIS total score is a sum of 3 assessments: Bleeding (scored 0-3), Erosion and Ulcers (scored 0-3), and Vascular Pattern (scored 0-2). The total score ranges from 0-8, with higher score indicating more severe disease. A negative change from baseline indicates improvement. |
| Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Baseline, Days 29 and 57 | Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 centimeters (cm) from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using GS. The GS is a stepwise grading system used for the evaluation of microscopic inflammation and histopathologic disease activity in UC. The microscopic appearance of the mucosa is categorized into 6 grades: Grade 0: architectural changes, Grade 1: chronic inflammatory infiltrate, Grade 2: lamina propria neutrophils and eosinophils, Grade 3: neutrophils in epithelium, Grade 4: crypt destruction and erosions or Grade 5: ulcerations, and each grade of the score is divided in 4 subcategories. A decrease of the Geboes grading system to Grades 0 or 1 would indicate mucosal healing. |
| Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Baseline, Days 29 and 57 | Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 cm from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using RIH. The RHI is an evaluative index, derived from the Geboes score and is designed to be reproducible and responsive to clinically meaningful change in disease activity over time. The total RHI score ranges from 0 (no disease activity) to 33 (severe disease activity). A negative change from baseline indicates improvement. |
| Time to Maximum Concentration (Tmax) of RO7049665 | Day 1 to Day 15 (predose) and Day 43 (post-dose) | — |
| Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Baseline, Days 29 and 57 | The MCS ranges from 0 to 12 and is a composite of 4 assessments: stool frequency, rectal bleeding, endoscopy (i.e., centrally read MCS-ES) and Physician Global Assessment (PGA). Each assessment was rated from 0-3, with higher score indicating more severe disease. Clinical response was defined as a decrease in the MCS of at least 3 points and at least 30% decrease from baseline. |
| 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 | ADA assays was used to detect anti-drug antibodies against RO7049665. Samples which were positive for anti-drug antibodies were further assessed using a neutralizing antibody assay. Participants were considered ADA positive if they were ADA negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response). |
| 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 (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 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 | — |
| 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 | — |
| Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Baseline, Days 29 and 57 | Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 cm from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using NHI. NHI is a validated index for assessing histological disease activity in UC. It is composed of three histological items defining five grades of disease activity: absence of significant histological disease (Grade 0), chronic inflammatory infiltrate with no acute inflammatory infiltrate (Grade 1), mildly active disease (Grade 2), moderately active disease (Grade 3), and severely active disease (Grade 4). The presence of ulceration on the biopsy specimen corresponds to severely active disease (Grade 4). A decrease of the NHI grading system to Grades 0 or 1 would indicate improvement. |
Countries
Georgia, Hungary, Moldova, Ukraine, United States
Participant flow
Recruitment details
Participants took part in this study at 4 investigative centers in 4 countries Georgia, Hungary, Moldova, Ukraine from 13 May 2019 to 22 July 2021.
Pre-assignment details
Participants with active ulcerative colitis (UC) were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period. | 9 |
| RO7049665 3.5 mg Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period. | 9 |
| RO7049665 7.5 mg Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period. | 27 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Participant Moved Out of the Country | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | RO7049665 3.5 mg | RO7049665 7.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 17.5 | 35.1 years STANDARD_DEVIATION 12.4 | 46.4 years STANDARD_DEVIATION 11.8 | 43.3 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 27 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 27 Participants | 45 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 13 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 14 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 27 |
| other Total, other adverse events | 4 / 9 | 6 / 9 | 23 / 27 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 1 / 27 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: From baseline up to safety follow-up visit on Day 99
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least 1 AE | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least one SAE | 0 Participants |
| RO7049665 3.5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least 1 AE | 6 Participants |
| RO7049665 3.5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least one SAE | 0 Participants |
| RO7049665 7.5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least 1 AE | 24 Participants |
| RO7049665 7.5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with at least one SAE | 1 Participants |
Secondary
Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665
Time frame: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Population: PK analysis population included participants who had received active treatment. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665 | Day 1: Dose 1 | 2030 h*ng/mL |
| Placebo | Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665 | Day 43: Dose 4 | 3520 h*ng/mL |
| RO7049665 3.5 mg | Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665 | Day 1: Dose 1 | 4520 h*ng/mL |
| RO7049665 3.5 mg | Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665 | Day 43: Dose 4 | 4110 h*ng/mL |
Secondary
Change From Baseline in Eosinophils
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 8, 22, 36, 57, 71 and follow-up visit on Day 99
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 43 (Pre-dose) | 0.000 10^9/L | Standard Deviation 0.062 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 22 | 0.008 10^9/L | Standard Deviation 0.072 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 71 | 0.031 10^9/L | Standard Deviation 0.076 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 36 | 0.014 10^9/L | Standard Deviation 0.087 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 29 (Pre-dose) | 0.021 10^9/L | Standard Deviation 0.197 |
| Placebo | Change From Baseline in Eosinophils | Baseline | 0.177 10^9/L | Standard Deviation 0.2 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 8 | -0.009 10^9/L | Standard Deviation 0.088 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 2 | -0.014 10^9/L | Standard Deviation 0.053 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 57 | 0.022 10^9/L | Standard Deviation 0.254 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 15 (Pre-dose) | -0.010 10^9/L | Standard Deviation 0.098 |
| Placebo | Change From Baseline in Eosinophils | Change from Baseline at Day 99 | -0.022 10^9/L | Standard Deviation 0.072 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 29 (Pre-dose) | 0.041 10^9/L | Standard Deviation 0.199 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Baseline | 0.233 10^9/L | Standard Deviation 0.275 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 2 | 0.047 10^9/L | Standard Deviation 0.088 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 8 | 0.213 10^9/L | Standard Deviation 0.141 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 15 (Pre-dose) | 0.080 10^9/L | Standard Deviation 0.17 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 22 | 0.286 10^9/L | Standard Deviation 0.214 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 36 | 0.490 10^9/L | Standard Deviation 0.34 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 43 (Pre-dose) | 0.194 10^9/L | Standard Deviation 0.21 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 57 | 0.203 10^9/L | Standard Deviation 0.232 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 71 | 0.135 10^9/L | Standard Deviation 0.155 |
| RO7049665 3.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 99 | 0.139 10^9/L | Standard Deviation 0.286 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 71 | 0.085 10^9/L | Standard Deviation 0.224 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 43 (Pre-dose) | 0.386 10^9/L | Standard Deviation 0.558 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 8 | 0.387 10^9/L | Standard Deviation 0.207 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Baseline | 0.204 10^9/L | Standard Deviation 0.129 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 57 | 0.378 10^9/L | Standard Deviation 0.599 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 2 | 0.047 10^9/L | Standard Deviation 0.081 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 29 (Pre-dose) | 0.318 10^9/L | Standard Deviation 0.408 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 22 | 1.373 10^9/L | Standard Deviation 1.613 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 99 | -0.019 10^9/L | Standard Deviation 0.166 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 36 | 1.234 10^9/L | Standard Deviation 0.837 |
| RO7049665 7.5 mg | Change From Baseline in Eosinophils | Change from Baseline at Day 15 (Pre-dose) | 0.283 10^9/L | Standard Deviation 0.486 |
Secondary
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS)
Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 centimeters (cm) from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using GS. The GS is a stepwise grading system used for the evaluation of microscopic inflammation and histopathologic disease activity in UC. The microscopic appearance of the mucosa is categorized into 6 grades: Grade 0: architectural changes, Grade 1: chronic inflammatory infiltrate, Grade 2: lamina propria neutrophils and eosinophils, Grade 3: neutrophils in epithelium, Grade 4: crypt destruction and erosions or Grade 5: ulcerations, and each grade of the score is divided in 4 subcategories. A decrease of the Geboes grading system to Grades 0 or 1 would indicate mucosal healing.
Time frame: Baseline, Days 29 and 57
Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Change from Baseline at Day 29 | -0.33 score on a scale | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Baseline | 4.56 score on a scale | Standard Deviation 0.88 |
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Change from Baseline at Day 57 | -0.89 score on a scale | Standard Deviation 1.9 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Change from Baseline at Day 29 | 0.78 score on a scale | Standard Deviation 2.49 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Baseline | 3.22 score on a scale | Standard Deviation 1.92 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Change from Baseline at Day 57 | 0.88 score on a scale | Standard Deviation 2.85 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Baseline | 3.54 score on a scale | Standard Deviation 2.04 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Change from Baseline at Day 57 | -0.54 score on a scale | Standard Deviation 1.82 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Geboes Score (GS) | Change from Baseline at Day 29 | -0.70 score on a scale | Standard Deviation 1.11 |
Secondary
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI)
Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 cm from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using NHI. NHI is a validated index for assessing histological disease activity in UC. It is composed of three histological items defining five grades of disease activity: absence of significant histological disease (Grade 0), chronic inflammatory infiltrate with no acute inflammatory infiltrate (Grade 1), mildly active disease (Grade 2), moderately active disease (Grade 3), and severely active disease (Grade 4). The presence of ulceration on the biopsy specimen corresponds to severely active disease (Grade 4). A decrease of the NHI grading system to Grades 0 or 1 would indicate improvement.
Time frame: Baseline, Days 29 and 57
Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Change from Baseline at Day 29 | -0.56 score on a scale | Standard Deviation 1.01 |
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Baseline | 3.11 score on a scale | Standard Deviation 0.78 |
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Change from Baseline at Day 57 | -0.78 score on a scale | Standard Deviation 1.48 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Change from Baseline at Day 29 | 0.33 score on a scale | Standard Deviation 1.94 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Baseline | 2.11 score on a scale | Standard Deviation 1.45 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Change from Baseline at Day 57 | 0.88 score on a scale | Standard Deviation 2.42 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Baseline | 2.42 score on a scale | Standard Deviation 1.68 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Change from Baseline at Day 57 | -0.25 score on a scale | Standard Deviation 1.29 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Nancy Histology Index (NHI) | Change from Baseline at Day 29 | -0.57 score on a scale | Standard Deviation 1.08 |
Secondary
Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI)
Mucosal biopsies were obtained during flexible sigmoidoscopy from the most affected area 10 to 20 cm from the anal verge. Biopsies were assessed by standard histology for changes in the inflammatory activity as measured using RIH. The RHI is an evaluative index, derived from the Geboes score and is designed to be reproducible and responsive to clinically meaningful change in disease activity over time. The total RHI score ranges from 0 (no disease activity) to 33 (severe disease activity). A negative change from baseline indicates improvement.
Time frame: Baseline, Days 29 and 57
Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Change from Baseline at Day 29 | -3.11 score on a scale | Standard Deviation 8.52 |
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Baseline | 18.78 score on a scale | Standard Deviation 7.19 |
| Placebo | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Change from Baseline at Day 57 | -6.22 score on a scale | Standard Deviation 8.91 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Change from Baseline at Day 29 | 3.89 score on a scale | Standard Deviation 11.85 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Baseline | 11.44 score on a scale | Standard Deviation 9.3 |
| RO7049665 3.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Change from Baseline at Day 57 | 5.38 score on a scale | Standard Deviation 16.83 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Baseline | 14.88 score on a scale | Standard Deviation 10.9 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Change from Baseline at Day 57 | -1.25 score on a scale | Standard Deviation 8.9 |
| RO7049665 7.5 mg | Change From Baseline in Histology Score of Sigmoid Colon Biopsies Using Robarts Histology Index (RHI) | Change from Baseline at Day 29 | -3.17 score on a scale | Standard Deviation 7.36 |
Secondary
Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES)
The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of 4 assessments, each rated from 0-3: stool frequency, rectal bleeding, endoscopy (i.e., centrally read MCS-ES) and Physician Global Assessment (PGA). Flexible sigmoidoscopy (or colonoscopy) was centrally read and scored using the MCS-ES scoring systems. The disease was considered as endoscopic normal or inactive if the MCS-ES (centrally read) was 0, mild (erythema, decreased vascular pattern) if MCS-ES was 1, moderate (marked erythema, absent vascular pattern, erosions) if MCS-ES was 2 and severe (spontaneous bleeding, ulceration) if MCS-ES was 3. The Endoscopy Subscore of the Mayo Score was modified so that a value of 1 did not include friability. A negative change from baseline indicates improvement.
Time frame: Baseline, Days 29 and 57
Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Change from Baseline at Day 29 | -0.22 score on a scale | Standard Deviation 0.83 |
| Placebo | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Baseline | 2.56 score on a scale | Standard Deviation 0.53 |
| Placebo | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Change from Baseline at Day 57 | -0.11 score on a scale | Standard Deviation 0.93 |
| RO7049665 3.5 mg | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Change from Baseline at Day 29 | -0.22 score on a scale | Standard Deviation 0.83 |
| RO7049665 3.5 mg | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Baseline | 2.44 score on a scale | Standard Deviation 0.53 |
| RO7049665 3.5 mg | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Change from Baseline at Day 57 | 0.00 score on a scale | Standard Deviation 0.53 |
| RO7049665 7.5 mg | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Baseline | 2.59 score on a scale | Standard Deviation 0.5 |
| RO7049665 7.5 mg | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Change from Baseline at Day 57 | -0.42 score on a scale | Standard Deviation 0.72 |
| RO7049665 7.5 mg | Change From Baseline in the Endoscopy Subscore of the Mayo Clinic Score (MCS-ES) | Change from Baseline at Day 29 | -0.54 score on a scale | Standard Deviation 0.98 |
Secondary
Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Flexible sigmoidoscopy (or colonoscopy) were centrally read and scored using the UCEIS scoring systems. The UCEIS total score is a sum of 3 assessments: Bleeding (scored 0-3), Erosion and Ulcers (scored 0-3), and Vascular Pattern (scored 0-2). The total score ranges from 0-8, with higher score indicating more severe disease. A negative change from baseline indicates improvement.
Time frame: Baseline, Days 29 and 57
Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Change from Baseline at Day 29 | -0.67 score on a scale | Standard Deviation 1.32 |
| Placebo | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Baseline | 4.33 score on a scale | Standard Deviation 1.12 |
| Placebo | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Change from Baseline at Day 57 | -0.22 score on a scale | Standard Deviation 1.56 |
| RO7049665 3.5 mg | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Change from Baseline at Day 29 | -0.22 score on a scale | Standard Deviation 1.79 |
| RO7049665 3.5 mg | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Baseline | 4.00 score on a scale | Standard Deviation 1.73 |
| RO7049665 3.5 mg | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Change from Baseline at Day 57 | 0.63 score on a scale | Standard Deviation 1.85 |
| RO7049665 7.5 mg | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Baseline | 3.85 score on a scale | Standard Deviation 0.86 |
| RO7049665 7.5 mg | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Change from Baseline at Day 57 | -0.71 score on a scale | Standard Deviation 1.33 |
| RO7049665 7.5 mg | Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | Change from Baseline at Day 29 | -0.71 score on a scale | Standard Deviation 1.52 |
Secondary
Change From Baseline in White Blood Cells (B Cells)
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 15 (Pre-dose) | 4.44 cells/µl | Standard Deviation 34.11 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 57 | -26.88 cells/µl | Standard Deviation 23.22 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 43 (Pre-dose) | 19.25 cells/µl | Standard Deviation 51.24 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 22 | 5.31 cells/µl | Standard Deviation 28.01 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 6 | 29.69 cells/µl | Standard Deviation 53.88 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 36 | -0.75 cells/µl | Standard Deviation 28.83 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 29 (Pre-dose) | -8.28 cells/µl | Standard Deviation 35.09 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 71 | -9.72 cells/µl | Standard Deviation 16.36 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 52 | 2.28 cells/µl | Standard Deviation 31.15 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 8 | 5.31 cells/µl | Standard Deviation 31.1 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 2 | -8.75 cells/µl | Standard Deviation 26.26 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 50 | 7.81 cells/µl | Standard Deviation 37.53 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 10 | 7.75 cells/µl | Standard Deviation 24.33 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Baseline | 117.39 cells/µl | Standard Deviation 51.86 |
| Placebo | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 48 | 2.39 cells/µl | Standard Deviation 25.68 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 50 | 28.00 cells/µl | Standard Deviation 53.38 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 2 | -30.06 cells/µl | Standard Deviation 35.54 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 6 | 27.94 cells/µl | Standard Deviation 115.62 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 8 | 29.17 cells/µl | Standard Deviation 73.38 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 10 | 37.72 cells/µl | Standard Deviation 53.45 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 15 (Pre-dose) | 30.61 cells/µl | Standard Deviation 59.27 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 22 | 18.06 cells/µl | Standard Deviation 51.74 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 29 (Pre-dose) | -5.06 cells/µl | Standard Deviation 38.13 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 36 | 17.50 cells/µl | Standard Deviation 69.03 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 43 (Pre-dose) | 23.13 cells/µl | Standard Deviation 55.97 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 48 | 22.88 cells/µl | Standard Deviation 47.57 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Baseline | 149.39 cells/µl | Standard Deviation 75.67 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 52 | 20.63 cells/µl | Standard Deviation 58.57 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 57 | 24.13 cells/µl | Standard Deviation 56.16 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 71 | 4.38 cells/µl | Standard Deviation 66.38 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 10 | 48.83 cells/µl | Standard Deviation 48.94 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 71 | 8.05 cells/µl | Standard Deviation 52.65 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 48 | 1.04 cells/µl | Standard Deviation 40.3 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 8 | 14.50 cells/µl | Standard Deviation 39.33 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 57 | 10.04 cells/µl | Standard Deviation 60.22 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 50 | 35.19 cells/µl | Standard Deviation 62.64 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 6 | -41.87 cells/µl | Standard Deviation 47.32 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Baseline | 158.20 cells/µl | Standard Deviation 76.23 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 29 (Pre-dose) | -7.02 cells/µl | Standard Deviation 33.59 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 22 | 25.65 cells/µl | Standard Deviation 52.69 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 52 | 59.60 cells/µl | Standard Deviation 53.87 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 36 | 22.52 cells/µl | Standard Deviation 39.02 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 15 (Pre-dose) | 17.24 cells/µl | Standard Deviation 46.26 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 2 | -43.08 cells/µl | Standard Deviation 36.06 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (B Cells) | Change from Baseline at Day 43 (Pre-dose) | 23.54 cells/µl | Standard Deviation 47.44 |
Secondary
Change From Baseline in White Blood Cells (Natural Killer (NK) Cells)
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 15 (Pre-dose) | 4.44 cells/µl | Standard Deviation 51.4 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 6 | 86.88 cells/µl | Standard Deviation 130.28 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 48 | 42.89 cells/µl | Standard Deviation 71.22 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 22 | 26.19 cells/µl | Standard Deviation 40.55 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 2 | 2.31 cells/µl | Standard Deviation 47.27 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 43 (Pre-dose) | -2.44 cells/µl | Standard Deviation 67.43 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 29 (Pre-dose) | -6.78 cells/µl | Standard Deviation 136.64 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 52 | 48.33 cells/µl | Standard Deviation 55.65 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 36 | 14.44 cells/µl | Standard Deviation 44.87 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 8 | 26.44 cells/µl | Standard Deviation 75.75 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 71 | 47.44 cells/µl | Standard Deviation 65.41 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Baseline | 146.44 cells/µl | Standard Deviation 71.8 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 10 | 53.94 cells/µl | Standard Deviation 55.97 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 57 | 28.69 cells/µl | Standard Deviation 119.08 |
| Placebo | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 50 | 31.88 cells/µl | Standard Deviation 108.11 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 50 | 46.19 cells/µl | Standard Deviation 65.72 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Baseline | 154.00 cells/µl | Standard Deviation 102.99 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 2 | 13.22 cells/µl | Standard Deviation 59.3 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 6 | 56.67 cells/µl | Standard Deviation 114.71 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 8 | 105.67 cells/µl | Standard Deviation 72.36 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 10 | 77.33 cells/µl | Standard Deviation 125.77 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 15 (Pre-dose) | 20.89 cells/µl | Standard Deviation 45.83 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 22 | 47.44 cells/µl | Standard Deviation 84.33 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 29 (Pre-dose) | -39.00 cells/µl | Standard Deviation 52.92 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 36 | 28.44 cells/µl | Standard Deviation 32.84 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 43 (Pre-dose) | -2.94 cells/µl | Standard Deviation 37.03 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 48 | 72.19 cells/µl | Standard Deviation 33.3 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 52 | 56.31 cells/µl | Standard Deviation 60.3 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 57 | 50.69 cells/µl | Standard Deviation 74.56 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 71 | 49.94 cells/µl | Standard Deviation 39.55 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 15 (Pre-dose) | -25.35 cells/µl | Standard Deviation 85.97 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 57 | 30.52 cells/µl | Standard Deviation 102.02 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 48 | 109.65 cells/µl | Standard Deviation 130.12 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 10 | 119.31 cells/µl | Standard Deviation 131.7 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 8 | 73.90 cells/µl | Standard Deviation 128.85 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 50 | 97.58 cells/µl | Standard Deviation 107 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 6 | 57.77 cells/µl | Standard Deviation 119.77 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Baseline | 227.24 cells/µl | Standard Deviation 157.93 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 52 | 111.38 cells/µl | Standard Deviation 137.55 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 29 (Pre-dose) | 40.84 cells/µl | Standard Deviation 165.59 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 2 | 34.56 cells/µl | Standard Deviation 157.84 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 36 | 75.46 cells/µl | Standard Deviation 109.53 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 22 | 93.81 cells/µl | Standard Deviation 167.15 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 71 | 35.19 cells/µl | Standard Deviation 88.44 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Natural Killer (NK) Cells) | Change from Baseline at Day 43 (Pre-dose) | -5.72 cells/µl | Standard Deviation 75.02 |
Secondary
Change From Baseline in White Blood Cells (Tregs, Teffs)
Time frame: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Baseline | 178.22 cells/µl | Standard Deviation 125.11 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Baseline | 513.11 cells/µl | Standard Deviation 249.55 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 15 (Pre-dose) | -3.80 cells/µl | Standard Deviation 11.57 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 71 | 80.89 cells/µl | Standard Deviation 138.9 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 2 | 35.36 cells/µl | Standard Deviation 166.81 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 57 | -16.50 cells/µl | Standard Deviation 63.83 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 57 | 1.63 cells/µl | Standard Deviation 154.15 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 6 | 130.75 cells/µl | Standard Deviation 183.96 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 43 (Pre-dose) | -0.29 cells/µl | Standard Deviation 58.42 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 52 | 117.60 cells/µl | Standard Deviation 160.56 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 8 | 96.50 cells/µl | Standard Deviation 152.39 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 22 | 5.17 cells/µl | Standard Deviation 5.89 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 50 | 79.63 cells/µl | Standard Deviation 210.91 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 10 | 99.08 cells/µl | Standard Deviation 271.08 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 6 | 12.17 cells/µl | Standard Deviation 22.53 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 48 | 73.88 cells/µl | Standard Deviation 166.61 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 15 (Pre-dose) | 145.07 cells/µl | Standard Deviation 226.1 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 36 | -9.00 cells/µl | Standard Deviation 56.32 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 43 (Pre-dose) | 55.50 cells/µl | Standard Deviation 174.27 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 22 | 85.25 cells/µl | Standard Deviation 140.67 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 29 (Pre-dose) | -3.75 cells/µl | Standard Deviation 6.55 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 36 | 48.13 cells/µl | Standard Deviation 174.33 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 29 (Pre-dose) | 2.67 cells/µl | Standard Deviation 189.2 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 71 | 17.89 cells/µl | Standard Deviation 64.96 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 29 (Pre-dose) | 5.67 cells/µl | Standard Deviation 81.4 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 36 | 4.57 cells/µl | Standard Deviation 11.92 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 52 | 50.60 cells/µl | Standard Deviation 17.31 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 22 | 31.25 cells/µl | Standard Deviation 64.06 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 43 (Pre-dose) | 4.00 cells/µl | Standard Deviation 13.32 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 8 | 3.00 cells/µl | Standard Deviation 15.32 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 15 (Pre-dose) | 56.21 cells/µl | Standard Deviation 72.6 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 48 | 2.71 cells/µl | Standard Deviation 12.46 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 2 | -2.83 cells/µl | Standard Deviation 9.33 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 10 | 24.83 cells/µl | Standard Deviation 113.33 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 50 | 5.43 cells/µl | Standard Deviation 14.53 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 50 | 18.38 cells/µl | Standard Deviation 72.51 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 8 | 27.38 cells/µl | Standard Deviation 63.78 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 52 | 1.63 cells/µl | Standard Deviation 7.5 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 10 | -8.25 cells/µl | Standard Deviation 6.76 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 6 | 63.08 cells/µl | Standard Deviation 107.79 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 57 | 0.71 cells/µl | Standard Deviation 11.46 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Baseline | 37.25 cells/µl | Standard Deviation 33.34 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 2 | 15.57 cells/µl | Standard Deviation 47.73 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 71 | 5.38 cells/µl | Standard Deviation 12.46 |
| Placebo | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 48 | 11.00 cells/µl | Standard Deviation 62.64 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 43 (Pre-dose) | 5.19 cells/µl | Standard Deviation 100.23 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Baseline | 42.14 cells/µl | Standard Deviation 25.07 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 2 | -24.33 cells/µl | Standard Deviation 19.51 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 6 | 61.80 cells/µl | Standard Deviation 31.22 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 8 | 66.00 cells/µl | Standard Deviation 68.26 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 10 | 27.20 cells/µl | Standard Deviation 18.99 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 15 (Pre-dose) | 16.29 cells/µl | Standard Deviation 28.42 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 22 | 76.00 cells/µl | Standard Deviation 70.04 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 29 (Pre-dose) | 15.57 cells/µl | Standard Deviation 18.74 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 36 | 56.80 cells/µl | Standard Deviation 57.37 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 43 (Pre-dose) | 36.80 cells/µl | Standard Deviation 26.12 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 48 | 74.50 cells/µl | Standard Deviation 48.63 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 50 | 110.40 cells/µl | Standard Deviation 57.33 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 52 | 93.20 cells/µl | Standard Deviation 39.16 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 57 | 44.00 cells/µl | Standard Deviation 28.47 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 71 | 16.67 cells/µl | Standard Deviation 42.32 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Baseline | 707.72 cells/µl | Standard Deviation 360.77 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 2 | -164.07 cells/µl | Standard Deviation 178.26 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 6 | 101.17 cells/µl | Standard Deviation 486.37 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 8 | 148.17 cells/µl | Standard Deviation 352.08 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 10 | 117.06 cells/µl | Standard Deviation 212.04 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 15 (Pre-dose) | 89.06 cells/µl | Standard Deviation 182.77 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 22 | 117.17 cells/µl | Standard Deviation 296.9 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 29 (Pre-dose) | 21.50 cells/µl | Standard Deviation 289.32 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 36 | -22.38 cells/µl | Standard Deviation 204.94 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 43 (Pre-dose) | 96.69 cells/µl | Standard Deviation 261.72 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 48 | 128.31 cells/µl | Standard Deviation 518.6 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 50 | 220.56 cells/µl | Standard Deviation 293.51 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 52 | 199.64 cells/µl | Standard Deviation 309.23 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 57 | 202.56 cells/µl | Standard Deviation 315.23 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 71 | 142.81 cells/µl | Standard Deviation 229.77 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Baseline | 282.78 cells/µl | Standard Deviation 226.36 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 2 | -83.00 cells/µl | Standard Deviation 109.3 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 8 | 12.89 cells/µl | Standard Deviation 159.82 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 10 | 41.78 cells/µl | Standard Deviation 125.23 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 15 (Pre-dose) | -68.33 cells/µl | Standard Deviation 119.93 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 22 | -23.89 cells/µl | Standard Deviation 247.21 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 29 (Pre-dose) | -81.56 cells/µl | Standard Deviation 170.89 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 36 | -23.81 cells/µl | Standard Deviation 72.26 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 6 | 5.33 cells/µl | Standard Deviation 242.6 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 48 | 26.44 cells/µl | Standard Deviation 213.36 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 50 | 49.06 cells/µl | Standard Deviation 153.58 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 52 | 41.79 cells/µl | Standard Deviation 143.04 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 57 | 52.81 cells/µl | Standard Deviation 200.84 |
| RO7049665 3.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 71 | 11.69 cells/µl | Standard Deviation 114.91 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 71 | -31.68 cells/µl | Standard Deviation 158.78 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 71 | 14.50 cells/µl | Standard Deviation 45.04 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 71 | 21.82 cells/µl | Standard Deviation 122.91 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Baseline | 272.40 cells/µl | Standard Deviation 134.63 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 57 | 35.08 cells/µl | Standard Deviation 58.97 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 48 | 63.07 cells/µl | Standard Deviation 148.04 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 2 | -43.87 cells/µl | Standard Deviation 90.73 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 52 | 81.64 cells/µl | Standard Deviation 83.51 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 6 | -16.23 cells/µl | Standard Deviation 96.79 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 50 | 115.79 cells/µl | Standard Deviation 149.9 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 8 | 169.34 cells/µl | Standard Deviation 138.21 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 8 | 67.40 cells/µl | Standard Deviation 127.56 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 48 | 149.96 cells/µl | Standard Deviation 129.48 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 57 | 25.33 cells/µl | Standard Deviation 130.86 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 10 | 115.35 cells/µl | Standard Deviation 216.62 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 43 (Pre-dose) | 33.22 cells/µl | Standard Deviation 53.39 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 50 | 83.10 cells/µl | Standard Deviation 154.47 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 15 (Pre-dose) | 8.00 cells/µl | Standard Deviation 105.56 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 36 | 110.61 cells/µl | Standard Deviation 72.94 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 6 | 87.37 cells/µl | Standard Deviation 66.84 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 22 | 68.52 cells/µl | Standard Deviation 152.91 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 29 (Pre-dose) | 27.66 cells/µl | Standard Deviation 29.09 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Baseline | 51.21 cells/µl | Standard Deviation 35.09 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 29 (Pre-dose) | -27.85 cells/µl | Standard Deviation 117.53 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 29 (Pre-dose) | -46.28 cells/µl | Standard Deviation 165.72 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 22 | 237.22 cells/µl | Standard Deviation 284.96 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 22 | 186.45 cells/µl | Standard Deviation 130.4 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 36 | 154.17 cells/µl | Standard Deviation 198.56 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 15 (Pre-dose) | 24.48 cells/µl | Standard Deviation 234.22 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 52 | 105.47 cells/µl | Standard Deviation 181.8 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 43 (Pre-dose) | 72.65 cells/µl | Standard Deviation 193.91 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 10 | 328.00 cells/µl | Standard Deviation 375.95 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 36 | 94.21 cells/µl | Standard Deviation 121.77 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 48 | 182.40 cells/µl | Standard Deviation 287.99 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 8 | 232.48 cells/µl | Standard Deviation 237.4 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 15 (Pre-dose) | 37.73 cells/µl | Standard Deviation 41.74 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 50 | 226.19 cells/µl | Standard Deviation 274.34 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 6 | 13.23 cells/µl | Standard Deviation 161.24 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 2 | -25.65 cells/µl | Standard Deviation 14.19 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 52 | 302.03 cells/µl | Standard Deviation 282.02 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 2 | -191.79 cells/µl | Standard Deviation 175.75 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD8 Teff: Change from Baseline at Day 43 (Pre-dose) | 21.15 cells/µl | Standard Deviation 108.79 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Change from Baseline at Day 57 | 28.70 cells/µl | Standard Deviation 194.94 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Teff: Baseline | 678.04 cells/µl | Standard Deviation 211.81 |
| RO7049665 7.5 mg | Change From Baseline in White Blood Cells (Tregs, Teffs) | CD4 Treg: Change from Baseline at Day 10 | 137.81 cells/µl | Standard Deviation 98.51 |
Secondary
Maximum Serum Concentration Observed (Cmax) of RO7049665
Time frame: Days 1 and 43: Pre-dose, 6 h and 12 h post-dose
Population: Pharmacokinetic (PK) analysis population included participants who had received active treatment. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Maximum Serum Concentration Observed (Cmax) of RO7049665 | Day 1: Dose 1 | 22.5 nanograms per milliliters (ng/mL) |
| Placebo | Maximum Serum Concentration Observed (Cmax) of RO7049665 | Day 43: Dose 4 | 38.7 nanograms per milliliters (ng/mL) |
| RO7049665 3.5 mg | Maximum Serum Concentration Observed (Cmax) of RO7049665 | Day 43: Dose 4 | 46.5 nanograms per milliliters (ng/mL) |
| RO7049665 3.5 mg | Maximum Serum Concentration Observed (Cmax) of RO7049665 | Day 1: Dose 1 | 47.6 nanograms per milliliters (ng/mL) |
Secondary
Number of Participants With Anti-Drug Antibodies (ADAs)
ADA assays was used to detect anti-drug antibodies against RO7049665. Samples which were positive for anti-drug antibodies were further assessed using a neutralizing antibody assay. Participants were considered ADA positive if they were ADA negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 4-fold (treatment-enhanced ADA response).
Time frame: Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43
Population: Immunogenicity population included all participants who had at least one pre-dose and one post-dose ADA assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-Drug Antibodies (ADAs) | ADA Positive: Treatment-Induced ADA Response | 0 Participants |
| Placebo | Number of Participants With Anti-Drug Antibodies (ADAs) | ADA Positive: Treatment-Enhanced ADA Response | 0 Participants |
| RO7049665 3.5 mg | Number of Participants With Anti-Drug Antibodies (ADAs) | ADA Positive: Treatment-Induced ADA Response | 6 Participants |
| RO7049665 3.5 mg | Number of Participants With Anti-Drug Antibodies (ADAs) | ADA Positive: Treatment-Enhanced ADA Response | 0 Participants |
| RO7049665 7.5 mg | Number of Participants With Anti-Drug Antibodies (ADAs) | ADA Positive: Treatment-Induced ADA Response | 18 Participants |
| RO7049665 7.5 mg | Number of Participants With Anti-Drug Antibodies (ADAs) | ADA Positive: Treatment-Enhanced ADA Response | 2 Participants |
Secondary
Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response
The MCS ranges from 0 to 12 and is a composite of 4 assessments: stool frequency, rectal bleeding, endoscopy (i.e., centrally read MCS-ES) and Physician Global Assessment (PGA). Each assessment was rated from 0-3, with higher score indicating more severe disease. Clinical response was defined as a decrease in the MCS of at least 3 points and at least 30% decrease from baseline.
Time frame: Baseline, Days 29 and 57
Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Day 29 | 11.1 percentage of participants |
| Placebo | Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Day 57 | 22.2 percentage of participants |
| RO7049665 3.5 mg | Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Day 57 | 50.0 percentage of participants |
| RO7049665 3.5 mg | Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Day 29 | 33.3 percentage of participants |
| RO7049665 7.5 mg | Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Day 29 | 16.7 percentage of participants |
| RO7049665 7.5 mg | Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response | Day 57 | 45.8 percentage of participants |
Secondary
Time to Maximum Concentration (Tmax) of RO7049665
Time frame: Day 1 to Day 15 (predose) and Day 43 (post-dose)
Population: Pharmacokinetic (PK) analysis population included participants who had received active treatment. Number analyzed is the number of participants with evaluable data at specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Concentration (Tmax) of RO7049665 | Day 1-Day 15: Dose 1 | 12.00 hour (h) |
| Placebo | Time to Maximum Concentration (Tmax) of RO7049665 | Day 43: Dose 4 | 18.06 hour (h) |
| RO7049665 3.5 mg | Time to Maximum Concentration (Tmax) of RO7049665 | Day 1-Day 15: Dose 1 | 24.00 hour (h) |
| RO7049665 3.5 mg | Time to Maximum Concentration (Tmax) of RO7049665 | Day 43: Dose 4 | 24.00 hour (h) |