Ulcerative Colitis (UC)
Conditions
Keywords
Ulcerative Colitis (UC), ABBV-323, Ravagalimab
Brief summary
Study M15-722 is a Phase 2a study to investigate the efficacy and safety of Ravagalimab (ABBV-323) in participants with moderate to severe UC who failed prior therapy.
Interventions
DRUGRavagalimab 600 mg
Ravagalimab 600 mg was administered intravenously (IV).
DRUGRavagalimab 300 mg
Ravagalimab 300 mg was administered subcutaneously (SC).
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures. * Diagnosis of UC for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of UC in the assessment of the Investigator, must be available. * Participant meets the following disease activity criteria: Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central review). * History of inadequate response, loss of response, or intolerance to one or more of the approved biologic therapies: infliximab, adalimumab, golimumab, vedolizumab, and/or tofacitinib (Note: If tofacitinib was received in a clinical trial, subject must have received open-label drug).
Exclusion criteria
* Participant having an active, chronic, or recurrent infection that based on Investigator's clinical assessment makes the participant an unsuitable candidate for the study. * Participant having any malignancy except for successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix. * Participant with history of dysplasia of the gastrointestinal tract or evidence of dysplasia in any biopsy performed during the screening endoscopy other than completely removed low-grade dysplastic lesions. * Laboratory values not meeting the following criteria : Serum aspartate transaminase (AST) and alanine transaminase (ALT) \<= 2\* upper limit of normal (ULN); Total white blood cell (WBC) count \>= 3.0\*10\^9/L.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Endoscopic Improvement During Induction Period | At Week 8 | Endoscopic Improvement is defined as Mayo endoscopic subscore of 0 or 1. Mayo endoscopic score is classified as 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern); 2=Moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Remission Per Adapted Mayo Score During Induction Period | At Week 8 | Clinical remission per Adapted Mayo score is defined as stool frequency subscore (SFS) \<=1, and not greater than baseline, rectal bleeding subscore (RBS) = 0, and endoscopic subscore \<=1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore confirmed by central reader, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer. |
| Percentage of Participants With Clinical Response Per Adapted Mayo Score During Induction Period | At Week 8 | Clinical response per Adapted Mayo score is defined as the decrease from Baseline \>= 2 points and \>= 30%, PLUS a decrease in RBS \>=1 or an absolute RBS \<=1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer. |
| Percentage of Participants With Clinical Response Per Partial Adapted Mayo Score | Up to Week 8 | Clinical response per Partial Adapted Mayo score is defined as decrease from baseline \>=1 points and \>=30%, PLUS a decrease in RBS \>= 1 or an absolute RBS \<=1. The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer. |
| Percentage of Participants With Clinical Remission Per Full Mayo Score During Induction Period in Participants With a Full Mayo Score of 6 to 12 at Baseline | At Week 8 | Clinical Remission per full Mayo score is defined as Full Mayo score \<=2 with no subscore \> 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Endoscopies were assessed by a central reader. Negative changes indicate improvement. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer. |
| Percentage of Participants With Endoscopic Remission During Induction Period | At Week 8 | Endoscopic remission is defined as Mayo endoscopic subscore = 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer. |
Countries
Canada, France, Germany, Hungary, Italy, Netherlands, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 42 participants were enrolled in the Induction Period to receive ravagalimab 600 mg intravenously (IV) followed by ravagalimab 300 mg subcutaneously (SC) up to Week 12. Participants who completed the Induction Period and achieved clinical response per partial adapted Mayo score at Week 12 entered the Maintenance Period to receive ravagalimab 300 mg SC up to Week 102.
Pre-assignment details
Prior to protocol version 4.0 this study was placebo-controlled. No participants were enrolled in the placebo group and therefore no results are presented for this arm.
Participants by arm
| Arm | Count |
|---|---|
| Ravagalimab 600 mg/ 300 mg Participants received ravagalimab 600 mg IV at Week 0 followed by ravagalimab 300 mg SC at Weeks 2, 4, 6, 8, and 10 in a 12-week Induction Period. Participants who achieved clinical response per partial adapted Mayo score at Week 12 of the Induction Period entered the Maintenance Period to receive ravagalimab 300 mg SC EOW from Week 12 through Week 102. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Period (Week 0 to Week 12) | Adverse Event | 1 |
| Induction Period (Week 0 to Week 12) | Lack of Efficacy | 10 |
| Induction Period (Week 0 to Week 12) | Withdrew consent | 2 |
| Maintenance Period (Week 12 to Week 102) | Lack of Efficacy | 2 |
| Maintenance Period (Week 12 to Week 102) | Reason not specified | 23 |
| Maintenance Period (Week 12 to Week 102) | Withdrew consent | 3 |
Baseline characteristics
| Characteristic | Ravagalimab 600 mg/ 300 mg |
|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 14.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race Non-White | 3 Participants |
| Race/Ethnicity, Customized Race White | 39 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 29 |
| other Total, other adverse events | 15 / 42 | 19 / 29 |
| serious Total, serious adverse events | 2 / 42 | 2 / 29 |
Outcome results
Primary
Percentage of Participants With Endoscopic Improvement During Induction Period
Endoscopic Improvement is defined as Mayo endoscopic subscore of 0 or 1. Mayo endoscopic score is classified as 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern); 2=Moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.
Time frame: At Week 8
Population: FAS included all enrolled participants who received at least 1 dose of ravagalimab. Data was reported only for the Induction Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravagalimab 600 mg/300 mg | Percentage of Participants With Endoscopic Improvement During Induction Period | 18.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Remission Per Adapted Mayo Score During Induction Period
Clinical remission per Adapted Mayo score is defined as stool frequency subscore (SFS) \<=1, and not greater than baseline, rectal bleeding subscore (RBS) = 0, and endoscopic subscore \<=1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore confirmed by central reader, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.
Time frame: At Week 8
Population: FAS included all enrolled participants who received at least 1 dose of ravagalimab and was used for all baseline and efficacy analyses. Data was reported only for the Induction Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravagalimab 600 mg/300 mg | Percentage of Participants With Clinical Remission Per Adapted Mayo Score During Induction Period | 9.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Remission Per Full Mayo Score During Induction Period in Participants With a Full Mayo Score of 6 to 12 at Baseline
Clinical Remission per full Mayo score is defined as Full Mayo score \<=2 with no subscore \> 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Endoscopies were assessed by a central reader. Negative changes indicate improvement. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer.
Time frame: At Week 8
Population: FAS included all enrolled participants who received at least 1 dose of ravagalimab. Overall number analysed is the number of participants available for analysis. Data was reported only for the Induction Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravagalimab 600 mg/300 mg | Percentage of Participants With Clinical Remission Per Full Mayo Score During Induction Period in Participants With a Full Mayo Score of 6 to 12 at Baseline | 7.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Response Per Adapted Mayo Score During Induction Period
Clinical response per Adapted Mayo score is defined as the decrease from Baseline \>= 2 points and \>= 30%, PLUS a decrease in RBS \>=1 or an absolute RBS \<=1. The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal), Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed), Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.
Time frame: At Week 8
Population: FAS included all enrolled participants who received at least 1 dose of ravagalimab. Data was reported only for the Induction Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravagalimab 600 mg/300 mg | Percentage of Participants With Clinical Response Per Adapted Mayo Score During Induction Period | 40.2 percentage of participants |
Secondary
Percentage of Participants With Clinical Response Per Partial Adapted Mayo Score
Clinical response per Partial Adapted Mayo score is defined as decrease from baseline \>=1 points and \>=30%, PLUS a decrease in RBS \>= 1 or an absolute RBS \<=1. The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: SFS, scored from 0 (normal number of stools) to 3 (5 or more stools more than normal); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to a nearest whole integer.
Time frame: Up to Week 8
Population: FAS included all enrolled participants who received at least 1 dose of ravagalimab. Data was reported only for the Induction Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravagalimab 600 mg/300 mg | Percentage of Participants With Clinical Response Per Partial Adapted Mayo Score | 57.1 percentage of participants |
Secondary
Percentage of Participants With Endoscopic Remission During Induction Period
Endoscopic remission is defined as Mayo endoscopic subscore = 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). Higher score indicates worsening of the disease. The number of responders is calculated based on the total number of participants and estimated response rate, rounding to the nearest whole integer.
Time frame: At Week 8
Population: FAS included all enrolled participants who received at least 1 dose of ravagalimab. Data was reported only for the Induction Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ravagalimab 600 mg/300 mg | Percentage of Participants With Endoscopic Remission During Induction Period | 0.0 percentage of participants |