Trial Outcomes & Findings for Double-Blinded, Placebo-Controlled Phase 1b Study for Safety, PK, Efficacy, PD of RO7049665 in Participants With Ulcerative Colitis (UC) (NCT NCT03943550)
NCT ID: NCT03943550
Last Updated: 2024-02-15
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
45 participants
Primary outcome timeframe
From baseline up to safety follow-up visit on Day 99
Results posted on
2024-02-15
Participant Flow
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.
Participants with active ulcerative colitis (UC) were enrolled in the study.
Participant milestones
| Measure |
Placebo
Participants received RO7049665 matching placebo, as subcutaneous (SC) injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
Participants received RO7049665, 3.5 milligrams (mg) as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
27
|
|
Overall Study
COMPLETED
|
9
|
8
|
23
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Participants received RO7049665 matching placebo, as subcutaneous (SC) injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
Participants received RO7049665, 3.5 milligrams (mg) as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
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.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
|
Overall Study
Progressive Disease
|
0
|
0
|
2
|
|
Overall Study
Participant Moved Out of the Country
|
0
|
1
|
0
|
Baseline Characteristics
Double-Blinded, Placebo-Controlled Phase 1b Study for Safety, PK, Efficacy, PD of RO7049665 in Participants With Ulcerative Colitis (UC)
Baseline characteristics by cohort
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
42.1 years
STANDARD_DEVIATION 17.5 • n=5 Participants
|
35.1 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
46.4 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
43.3 years
STANDARD_DEVIATION 13.6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From baseline up to safety follow-up visit on Day 99Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with at least 1 AE
|
4 Participants
|
6 Participants
|
24 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with at least one SAE
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=27 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
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.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of RO7049665
Day 1-Day 15: Dose 1
|
12.00 hour (h)
Interval 6.0 to 24.0
|
24.00 hour (h)
Interval 6.0 to 72.08
|
—
|
|
Time to Maximum Concentration (Tmax) of RO7049665
Day 43: Dose 4
|
18.06 hour (h)
Interval 12.0 to 72.57
|
24.00 hour (h)
Interval 12.0 to 73.17
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 43: Pre-dose, 6 h and 12 h post-dosePopulation: Pharmacokinetic (PK) analysis population included participants who had received active treatment. Number analyzed is the number of participants with evaluable data at specified timepoint.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=27 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
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.
|
|---|---|---|---|
|
Maximum Serum Concentration Observed (Cmax) of RO7049665
Day 1: Dose 1
|
22.5 nanograms per milliliters (ng/mL)
Interval 8.59 to 63.7
|
47.6 nanograms per milliliters (ng/mL)
Interval 13.9 to 250.0
|
—
|
|
Maximum Serum Concentration Observed (Cmax) of RO7049665
Day 43: Dose 4
|
38.7 nanograms per milliliters (ng/mL)
Interval 21.8 to 65.4
|
46.5 nanograms per milliliters (ng/mL)
Interval 20.2 to 109.0
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 43: Pre-dose, 6 h and 12 h post-dosePopulation: PK analysis population included participants who had received active treatment. Number analyzed is the number of participants with evaluable data at specified timepoint.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=27 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
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.
|
|---|---|---|---|
|
Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665
Day 1: Dose 1
|
2030 h*ng/mL
Interval 1020.0 to 3550.0
|
4520 h*ng/mL
Interval 1780.0 to 15100.0
|
—
|
|
Area Under the Serum Concentration-time Curve Extrapolated to Infinity (AUCinf) of RO7049665
Day 43: Dose 4
|
3520 h*ng/mL
Interval 1830.0 to 5740.0
|
4110 h*ng/mL
Interval 2200.0 to 8240.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 57Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
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
|
2.44 score on a scale
Standard Deviation 0.53
|
2.59 score on a scale
Standard Deviation 0.50
|
|
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
|
-0.22 score on a scale
Standard Deviation 0.83
|
-0.54 score on a scale
Standard Deviation 0.98
|
|
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
|
0.00 score on a scale
Standard Deviation 0.53
|
-0.42 score on a scale
Standard Deviation 0.72
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 57Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Change From Baseline in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Baseline
|
4.33 score on a scale
Standard Deviation 1.12
|
4.00 score on a scale
Standard Deviation 1.73
|
3.85 score on a scale
Standard Deviation 0.86
|
|
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
|
-0.22 score on a scale
Standard Deviation 1.79
|
-0.71 score on a scale
Standard Deviation 1.52
|
|
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
|
0.63 score on a scale
Standard Deviation 1.85
|
-0.71 score on a scale
Standard Deviation 1.33
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 57Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=26 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
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
|
3.22 score on a scale
Standard Deviation 1.92
|
3.54 score on a scale
Standard Deviation 2.04
|
|
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 1.90
|
0.88 score on a scale
Standard Deviation 2.85
|
-0.54 score on a scale
Standard Deviation 1.82
|
|
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
|
0.78 score on a scale
Standard Deviation 2.49
|
-0.70 score on a scale
Standard Deviation 1.11
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 57Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=26 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
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
|
5.38 score on a scale
Standard Deviation 16.83
|
-1.25 score on a scale
Standard Deviation 8.90
|
|
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
|
11.44 score on a scale
Standard Deviation 9.30
|
14.88 score on a scale
Standard Deviation 10.90
|
|
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
|
3.89 score on a scale
Standard Deviation 11.85
|
-3.17 score on a scale
Standard Deviation 7.36
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 57Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=26 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
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
|
2.11 score on a scale
Standard Deviation 1.45
|
2.42 score on a scale
Standard Deviation 1.68
|
|
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
|
0.33 score on a scale
Standard Deviation 1.94
|
-0.57 score on a scale
Standard Deviation 1.08
|
|
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
|
0.88 score on a scale
Standard Deviation 2.42
|
-0.25 score on a scale
Standard Deviation 1.29
|
SECONDARY outcome
Timeframe: Baseline, Days 29 and 57Population: ITT population included all randomized participants. Number analyzed is the number of participants with evaluable data at specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response
Day 29
|
11.1 percentage of participants
Interval 0.28 to 48.25
|
33.3 percentage of participants
Interval 7.49 to 70.07
|
16.7 percentage of participants
Interval 4.74 to 37.38
|
|
Percentage of Participants With Mayo Clinic Score (MCS) Clinical Response
Day 57
|
22.2 percentage of participants
Interval 2.81 to 60.01
|
50.0 percentage of participants
Interval 15.7 to 84.3
|
45.8 percentage of participants
Interval 25.55 to 67.18
|
SECONDARY outcome
Timeframe: Baseline; Post-dose on Days 8, 22, 57, 71 and 99; Pre-dose on Days 15, 29 and 43Population: Immunogenicity population included all participants who had at least one pre-dose and one post-dose ADA assessment.
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).
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Number of Participants With Anti-Drug Antibodies (ADAs)
ADA Positive: Treatment-Induced ADA Response
|
0 Participants
|
6 Participants
|
18 Participants
|
|
Number of Participants With Anti-Drug Antibodies (ADAs)
ADA Positive: Treatment-Enhanced ADA Response
|
0 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71Population: 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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
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
|
61.80 cells/µl
Standard Deviation 31.22
|
87.37 cells/µl
Standard Deviation 66.84
|
|
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
|
66.00 cells/µl
Standard Deviation 68.26
|
169.34 cells/µl
Standard Deviation 138.21
|
|
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
|
27.20 cells/µl
Standard Deviation 18.99
|
137.81 cells/µl
Standard Deviation 98.51
|
|
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
|
16.29 cells/µl
Standard Deviation 28.42
|
37.73 cells/µl
Standard Deviation 41.74
|
|
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
|
15.57 cells/µl
Standard Deviation 18.74
|
27.66 cells/µl
Standard Deviation 29.09
|
|
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
|
56.80 cells/µl
Standard Deviation 57.37
|
110.61 cells/µl
Standard Deviation 72.94
|
|
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
|
36.80 cells/µl
Standard Deviation 26.12
|
33.22 cells/µl
Standard Deviation 53.39
|
|
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
|
74.50 cells/µl
Standard Deviation 48.63
|
149.96 cells/µl
Standard Deviation 129.48
|
|
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
|
110.40 cells/µl
Standard Deviation 57.33
|
115.79 cells/µl
Standard Deviation 149.90
|
|
Change From Baseline in White Blood Cells (Tregs, Teffs)
CD4 Treg: Change from Baseline at Day 52
|
1.63 cells/µl
Standard Deviation 7.50
|
93.20 cells/µl
Standard Deviation 39.16
|
81.64 cells/µl
Standard Deviation 83.51
|
|
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
|
44.00 cells/µl
Standard Deviation 28.47
|
35.08 cells/µl
Standard Deviation 58.97
|
|
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
|
76.00 cells/µl
Standard Deviation 70.04
|
186.45 cells/µl
Standard Deviation 130.40
|
|
Change From Baseline in White Blood Cells (Tregs, Teffs)
CD4 Teff: Baseline
|
513.11 cells/µl
Standard Deviation 249.55
|
707.72 cells/µl
Standard Deviation 360.77
|
678.04 cells/µl
Standard Deviation 211.81
|
|
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
|
-164.07 cells/µl
Standard Deviation 178.26
|
-191.79 cells/µl
Standard Deviation 175.75
|
|
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
|
101.17 cells/µl
Standard Deviation 486.37
|
13.23 cells/µl
Standard Deviation 161.24
|
|
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
|
16.67 cells/µl
Standard Deviation 42.32
|
14.50 cells/µl
Standard Deviation 45.04
|
|
Change From Baseline in White Blood Cells (Tregs, Teffs)
CD8 Teff: Baseline
|
178.22 cells/µl
Standard Deviation 125.11
|
282.78 cells/µl
Standard Deviation 226.36
|
272.40 cells/µl
Standard Deviation 134.63
|
|
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
|
-83.00 cells/µl
Standard Deviation 109.30
|
-43.87 cells/µl
Standard Deviation 90.73
|
|
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
|
41.78 cells/µl
Standard Deviation 125.23
|
115.35 cells/µl
Standard Deviation 216.62
|
|
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 72.60
|
-68.33 cells/µl
Standard Deviation 119.93
|
8.00 cells/µl
Standard Deviation 105.56
|
|
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
|
-23.89 cells/µl
Standard Deviation 247.21
|
68.52 cells/µl
Standard Deviation 152.91
|
|
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
|
148.17 cells/µl
Standard Deviation 352.08
|
232.48 cells/µl
Standard Deviation 237.40
|
|
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
|
117.06 cells/µl
Standard Deviation 212.04
|
328.00 cells/µl
Standard Deviation 375.95
|
|
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 226.10
|
89.06 cells/µl
Standard Deviation 182.77
|
24.48 cells/µl
Standard Deviation 234.22
|
|
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
|
117.17 cells/µl
Standard Deviation 296.90
|
237.22 cells/µl
Standard Deviation 284.96
|
|
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 189.20
|
21.50 cells/µl
Standard Deviation 289.32
|
-46.28 cells/µl
Standard Deviation 165.72
|
|
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
|
-22.38 cells/µl
Standard Deviation 204.94
|
154.17 cells/µl
Standard Deviation 198.56
|
|
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
|
96.69 cells/µl
Standard Deviation 261.72
|
72.65 cells/µl
Standard Deviation 193.91
|
|
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
|
128.31 cells/µl
Standard Deviation 518.60
|
182.40 cells/µl
Standard Deviation 287.99
|
|
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
|
220.56 cells/µl
Standard Deviation 293.51
|
226.19 cells/µl
Standard Deviation 274.34
|
|
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
|
199.64 cells/µl
Standard Deviation 309.23
|
302.03 cells/µl
Standard Deviation 282.02
|
|
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
|
202.56 cells/µl
Standard Deviation 315.23
|
28.70 cells/µl
Standard Deviation 194.94
|
|
Change From Baseline in White Blood Cells (Tregs, Teffs)
CD4 Teff: Change from Baseline at Day 71
|
80.89 cells/µl
Standard Deviation 138.90
|
142.81 cells/µl
Standard Deviation 229.77
|
-31.68 cells/µl
Standard Deviation 158.78
|
|
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
|
5.33 cells/µl
Standard Deviation 242.60
|
-16.23 cells/µl
Standard Deviation 96.79
|
|
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
|
12.89 cells/µl
Standard Deviation 159.82
|
67.40 cells/µl
Standard Deviation 127.56
|
|
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 81.40
|
-81.56 cells/µl
Standard Deviation 170.89
|
-27.85 cells/µl
Standard Deviation 117.53
|
|
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
|
-23.81 cells/µl
Standard Deviation 72.26
|
94.21 cells/µl
Standard Deviation 121.77
|
|
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
|
5.19 cells/µl
Standard Deviation 100.23
|
21.15 cells/µl
Standard Deviation 108.79
|
|
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
|
26.44 cells/µl
Standard Deviation 213.36
|
63.07 cells/µl
Standard Deviation 148.04
|
|
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
|
49.06 cells/µl
Standard Deviation 153.58
|
83.10 cells/µl
Standard Deviation 154.47
|
|
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
|
41.79 cells/µl
Standard Deviation 143.04
|
105.47 cells/µl
Standard Deviation 181.80
|
|
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
|
52.81 cells/µl
Standard Deviation 200.84
|
25.33 cells/µl
Standard Deviation 130.86
|
|
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
|
11.69 cells/µl
Standard Deviation 114.91
|
21.82 cells/µl
Standard Deviation 122.91
|
|
Change From Baseline in White Blood Cells (Tregs, Teffs)
CD4 Treg: Baseline
|
37.25 cells/µl
Standard Deviation 33.34
|
42.14 cells/µl
Standard Deviation 25.07
|
51.21 cells/µl
Standard Deviation 35.09
|
|
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
|
-24.33 cells/µl
Standard Deviation 19.51
|
-25.65 cells/µl
Standard Deviation 14.19
|
SECONDARY outcome
Timeframe: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71Population: 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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Change From Baseline in White Blood Cells (Natural Killer (NK) Cells)
Baseline
|
146.44 cells/µl
Standard Deviation 71.80
|
154.00 cells/µl
Standard Deviation 102.99
|
227.24 cells/µl
Standard Deviation 157.93
|
|
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
|
56.67 cells/µl
Standard Deviation 114.71
|
57.77 cells/µl
Standard Deviation 119.77
|
|
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
|
105.67 cells/µl
Standard Deviation 72.36
|
73.90 cells/µl
Standard Deviation 128.85
|
|
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
|
13.22 cells/µl
Standard Deviation 59.30
|
34.56 cells/µl
Standard Deviation 157.84
|
|
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
|
77.33 cells/µl
Standard Deviation 125.77
|
119.31 cells/µl
Standard Deviation 131.70
|
|
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 51.40
|
20.89 cells/µl
Standard Deviation 45.83
|
-25.35 cells/µl
Standard Deviation 85.97
|
|
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
|
47.44 cells/µl
Standard Deviation 84.33
|
93.81 cells/µl
Standard Deviation 167.15
|
|
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
|
-39.00 cells/µl
Standard Deviation 52.92
|
40.84 cells/µl
Standard Deviation 165.59
|
|
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
|
28.44 cells/µl
Standard Deviation 32.84
|
75.46 cells/µl
Standard Deviation 109.53
|
|
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
|
-2.94 cells/µl
Standard Deviation 37.03
|
-5.72 cells/µl
Standard Deviation 75.02
|
|
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
|
72.19 cells/µl
Standard Deviation 33.30
|
109.65 cells/µl
Standard Deviation 130.12
|
|
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
|
46.19 cells/µl
Standard Deviation 65.72
|
97.58 cells/µl
Standard Deviation 107.00
|
|
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
|
56.31 cells/µl
Standard Deviation 60.30
|
111.38 cells/µl
Standard Deviation 137.55
|
|
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
|
50.69 cells/µl
Standard Deviation 74.56
|
30.52 cells/µl
Standard Deviation 102.02
|
|
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
|
49.94 cells/µl
Standard Deviation 39.55
|
35.19 cells/µl
Standard Deviation 88.44
|
SECONDARY outcome
Timeframe: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 6, 8, 10, 22, 36, 48, 50, 52, 57, 71Population: 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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 57
|
-26.88 cells/µl
Standard Deviation 23.22
|
24.13 cells/µl
Standard Deviation 56.16
|
10.04 cells/µl
Standard Deviation 60.22
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 71
|
-9.72 cells/µl
Standard Deviation 16.36
|
4.38 cells/µl
Standard Deviation 66.38
|
8.05 cells/µl
Standard Deviation 52.65
|
|
Change From Baseline in White Blood Cells (B Cells)
Baseline
|
117.39 cells/µl
Standard Deviation 51.86
|
149.39 cells/µl
Standard Deviation 75.67
|
158.20 cells/µl
Standard Deviation 76.23
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 2
|
-8.75 cells/µl
Standard Deviation 26.26
|
-30.06 cells/µl
Standard Deviation 35.54
|
-43.08 cells/µl
Standard Deviation 36.06
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 6
|
29.69 cells/µl
Standard Deviation 53.88
|
27.94 cells/µl
Standard Deviation 115.62
|
-41.87 cells/µl
Standard Deviation 47.32
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 8
|
5.31 cells/µl
Standard Deviation 31.10
|
29.17 cells/µl
Standard Deviation 73.38
|
14.50 cells/µl
Standard Deviation 39.33
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 10
|
7.75 cells/µl
Standard Deviation 24.33
|
37.72 cells/µl
Standard Deviation 53.45
|
48.83 cells/µl
Standard Deviation 48.94
|
|
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
|
30.61 cells/µl
Standard Deviation 59.27
|
17.24 cells/µl
Standard Deviation 46.26
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 22
|
5.31 cells/µl
Standard Deviation 28.01
|
18.06 cells/µl
Standard Deviation 51.74
|
25.65 cells/µl
Standard Deviation 52.69
|
|
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
|
-5.06 cells/µl
Standard Deviation 38.13
|
-7.02 cells/µl
Standard Deviation 33.59
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 36
|
-0.75 cells/µl
Standard Deviation 28.83
|
17.50 cells/µl
Standard Deviation 69.03
|
22.52 cells/µl
Standard Deviation 39.02
|
|
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
|
23.13 cells/µl
Standard Deviation 55.97
|
23.54 cells/µl
Standard Deviation 47.44
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 48
|
2.39 cells/µl
Standard Deviation 25.68
|
22.88 cells/µl
Standard Deviation 47.57
|
1.04 cells/µl
Standard Deviation 40.30
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 50
|
7.81 cells/µl
Standard Deviation 37.53
|
28.00 cells/µl
Standard Deviation 53.38
|
35.19 cells/µl
Standard Deviation 62.64
|
|
Change From Baseline in White Blood Cells (B Cells)
Change from Baseline at Day 52
|
2.28 cells/µl
Standard Deviation 31.15
|
20.63 cells/µl
Standard Deviation 58.57
|
59.60 cells/µl
Standard Deviation 53.87
|
SECONDARY outcome
Timeframe: Baseline; Pre-dose: Days 15, 29 and 43; Post-dose: Days 2, 8, 22, 36, 57, 71 and follow-up visit on Day 99Population: 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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 Participants
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 Participants
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Change From Baseline in Eosinophils
Baseline
|
0.177 10^9/L
Standard Deviation 0.200
|
0.233 10^9/L
Standard Deviation 0.275
|
0.204 10^9/L
Standard Deviation 0.129
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 2
|
-0.014 10^9/L
Standard Deviation 0.053
|
0.047 10^9/L
Standard Deviation 0.088
|
0.047 10^9/L
Standard Deviation 0.081
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 8
|
-0.009 10^9/L
Standard Deviation 0.088
|
0.213 10^9/L
Standard Deviation 0.141
|
0.387 10^9/L
Standard Deviation 0.207
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 15 (Pre-dose)
|
-0.010 10^9/L
Standard Deviation 0.098
|
0.080 10^9/L
Standard Deviation 0.170
|
0.283 10^9/L
Standard Deviation 0.486
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 22
|
0.008 10^9/L
Standard Deviation 0.072
|
0.286 10^9/L
Standard Deviation 0.214
|
1.373 10^9/L
Standard Deviation 1.613
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 29 (Pre-dose)
|
0.021 10^9/L
Standard Deviation 0.197
|
0.041 10^9/L
Standard Deviation 0.199
|
0.318 10^9/L
Standard Deviation 0.408
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 36
|
0.014 10^9/L
Standard Deviation 0.087
|
0.490 10^9/L
Standard Deviation 0.340
|
1.234 10^9/L
Standard Deviation 0.837
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 43 (Pre-dose)
|
0.000 10^9/L
Standard Deviation 0.062
|
0.194 10^9/L
Standard Deviation 0.210
|
0.386 10^9/L
Standard Deviation 0.558
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 57
|
0.022 10^9/L
Standard Deviation 0.254
|
0.203 10^9/L
Standard Deviation 0.232
|
0.378 10^9/L
Standard Deviation 0.599
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 71
|
0.031 10^9/L
Standard Deviation 0.076
|
0.135 10^9/L
Standard Deviation 0.155
|
0.085 10^9/L
Standard Deviation 0.224
|
|
Change From Baseline in Eosinophils
Change from Baseline at Day 99
|
-0.022 10^9/L
Standard Deviation 0.072
|
0.139 10^9/L
Standard Deviation 0.286
|
-0.019 10^9/L
Standard Deviation 0.166
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
RO7049665 3.5 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
RO7049665 7.5 mg
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=9 participants at risk
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 participants at risk
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 participants at risk
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
3.7%
1/27 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
Other adverse events
| Measure |
Placebo
n=9 participants at risk
Participants received RO7049665 matching placebo, as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 3.5 mg
n=9 participants at risk
Participants received RO7049665, 3.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
RO7049665 7.5 mg
n=27 participants at risk
Participants received RO7049665, 7.5 mg as SC injection, every 2 weeks for 4 doses up to Day 43 of the treatment period.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
11.1%
1/9 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
7.4%
2/27 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Blood and lymphatic system disorders
Eosinophilia
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
48.1%
13/27 • Number of events 15 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
3.7%
1/27 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
7.4%
2/27 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Gastrointestinal disorders
Haemorrhoids
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
22.2%
2/9 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
General disorders
Injection site reaction
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
55.6%
5/9 • Number of events 17 • From baseline up to safety follow-up visit on Day 99
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.
|
66.7%
18/27 • Number of events 49 • From baseline up to safety follow-up visit on Day 99
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.
|
|
General disorders
Oedema peripheral
|
11.1%
1/9 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Infections and infestations
Gastroenteritis
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Infections and infestations
Urinary tract infection
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Injury, poisoning and procedural complications
Injection related reaction
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
7.4%
2/27 • Number of events 4 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
7.4%
2/27 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Investigations
Aspartate aminotransferase increased
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Investigations
Platelet count decreased
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
7.4%
2/27 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
3.7%
1/27 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
11.1%
1/9 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Nervous system disorders
Headache
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
7.4%
2/27 • Number of events 2 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.1%
1/9 • Number of events 1 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/9 • From baseline up to safety follow-up visit on Day 99
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.
|
0.00%
0/27 • From baseline up to safety follow-up visit on Day 99
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER