Ulcerative Colitis
Conditions
Keywords
ulcerative colitis, moderate, severe
Brief summary
Phase 2 induction study with a long-term extension (LTE) period in participants with moderate to severe ulcerative colitis (UC).
Detailed description
This is a randomized, multicenter, double-blind, placebo-controlled, multiple dose exploratory Phase 2 induction study with a long-term extension (LTE) period in participants with moderate to severe ulcerative colitis (UC).
Interventions
DRUGNX-13 250mg
NX-13 250mg tablet, plus 2 placebo tablets
DRUGNX-13 750mg
NX-13 250mg tablets times 3 to equal 750mg
DRUGNX-13 Placebo
NX-13 Placebo tablets times 3 for blinding purposes
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult subjects aged 18 to 75 years (inclusive) * Diagnosis of UC ≥ 90 days before screening confirmed by histologic evidence * Active UC defined as a total Mayo Score (MMS) of ≥ 5 (inclusive) at baseline * ES ≥ 2 within 14 days prior to randomization * RBS ≥ 1.
Exclusion criteria
* Severe extensive colitis as evidenced by physician judgment that the participant is likely to require hospitalization for medical care or surgical intervention of any kind for UC (e.g., colectomy) within the 12 weeks after randomization; * Current evidence of fulminant colitis, toxic megacolon or recent history (within 6 months prior to screening) of toxic megacolon, or bowel perforation * Diagnosis of Crohn's disease (CD) or indeterminate colitis, or the presence or history of a fistula consistent with CD * Diagnosis of microscopic colitis, ischemic colitis, or radiation colitis * Bacterial or parasitic pathogenic enteric infection;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Mayo Score (MMS) at Week 12 | Baseline, Week 12 | The MMS ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency \[SFS\], rectal bleeding \[RBS\] and finding on endoscopy \[ES\]), each of which ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. A negative change in MMS score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Induction Period | Baseline up to Week 12 | Treatment-emergent adverse events (TEAEs) were defined as AEs that occurred after the participant received first dose of study treatment or if a pre-existing condition worsens in severity or becomes serious after receiving the first dose of study treatment until 21 days after the date and time of last dose of study drug. A summary of other non-serious AEs and all serious AEs, regardless of causality, is located in the Reported AE section. |
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Induction Period | Baseline up to Week 12 | SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality, is located in the Reported AE section. |
| Number of Participants With Clinical Remission Per MMS at Week 12 | Week 12 | Clinical Remission per MMS was defined as achieving MMS \<=2, with RBS =0, SFS \<=1 and not greater than baseline, and ES \<=1. The MMS ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (SFS, RBS, and ES), each of which ranges from 0 (normal) to 3 (severe disease). A lower MMS indicates better health status. |
| Number of Participants With MMS <=2 at Week 12 | Week 12 | The MMS ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (SFS, RBS, and ES), each of which ranges from 0 (normal) to 3 (severe disease). A lower MMS indicates better health status. |
| Number of Participants With Robarts Histopathology Index (RHI) Score <=3 at Week 12 | Week 12 | The Robarts Histopathology Index (RHI) score is used to assess the disease severity. The RHI is defined as the sum of four weighted items from Geboes: Grade 1: lamina propria chronic inflammation; Grade 2B: lamina propria neutrophils; Grade 3: epithelial neutrophils; Grade 5: surface epithelial injury. Total RHI score ranges from 0 (no disease activity) to 33 (severe disease activity) with a higher score indicating more severity. |
| Number of Participants With Clinical Response Per MMS at Week 12 | Baseline, Week 12 | Clinical Response was defined as \>=2 Points and \>=30% decrease from baseline in MMS with \>=1 point decrease in RBS or RBS \<=1. The MMS ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (SFS, RBS, and ES) each of which ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. |
| Number of Participants With Endoscopic Response at Week 12 | Week 12 | Endoscopic Response was defined as ES \<=1. The ES subscore of the MMS ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. |
| Number of Participants With Endoscopic Remission at Week 12 | Week 12 | Endoscopic Remission was defined as ES =0. The ES subscore of the MMS ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. |
| Number of Participants With Endoscopic-histologic Mucosal Improvement at Week 12 | Week 12 | Endoscopic-histologic Mucosal Improvement was defined as ES \<=1 and Geboes score \<2.0. The ES subscore of the MMS ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. The Geboes scoring system is a stepwise ordinal grading system for histological assessment of disease severity in UC. The Geboes score includes 7 histological items (Grade 0 Grade 5) with a total score summed to a continuous variable, ranging from 0 to 22. Lower Geboes scores indicate better health status. |
| Number of Participants With Histologic Endoscopic Mucosal Improvement (HEMI) at Week 12 | Week 12 | HEMI was defined as ES \<=1 and Geboes score \<3.1. The ES subscore of the MMS ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. The Geboes scoring system is a stepwise ordinal grading system for histological assessment of disease severity in UC. The Geboes score includes 7 histological items (Grade 0 Grade 5) with a total score summed to a continuous variable, ranging from 0 to 22. Lower Geboes scores indicate better health status. |
| Number of Participants With Histologic Endoscopic Mucosal Remission (HEMR) at Week 12 | Week 12 | HEMR was defined as ES = 0 and Geboes score \<2.0. The ES subscore of the MMS ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. The Geboes scoring system is a stepwise ordinal grading system for histological assessment of disease severity in UC. The Geboes score includes 7 histological items (Grade 0 Grade 5) with a total score summed to a continuous variable, ranging from 0 to 22. Lower Geboes scores indicate better health status. |
| Number of Participants With Symptomatic Remission at Week 12 | Baseline, Week 12 | Symptomatic remission was defined as RBS = 0 and (i) SFS = 0 or (ii) SFS = 1 with baseline SFS \>2, at Week 12. The MMS ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (SFS, RBS, and ES) each of which ranges from 0 (normal) to 3 (severe disease) with lower scores indicating better health status. |
| Number of Participants With Clinical Response Per Partial MMS at Week 4 | Baseline, Week 4 | Clinical response per partial MMS was defined as achieving \>=1 points and \>=30% decrease from baseline in partial MMS, with \>=1 point decrease in RBS or RBS \<=1. Partial MMS ranges from 0 (normal or inactive disease) to 6 (severe disease) and is calculated as the sum of 2 subscores (SFS and RBS), each of which ranges from 0 (normal) to 3 (severe disease). A lower partial MMS indicates better health status. |
| Number of Participants With Abdominal Pain Score = 0 at Week 12 | Week 12 | Participants rated their abdominal pain on a scale from 0 (no pain) to 10 (worst imaginable pain), with higher scores indicating more pain. |
| Number of Participants With Rectal Urgency Score = 0 at Week 12 | Week 12 | The rectal urgency score is based on the number of times participants must rush to the toilet to have a bowel movement. The score ranges from 0 (2 or fewer events) to 10 (12 or more events), with higher scores representing more severe symptoms. |
Countries
Belgium, Italy, Poland, United States
Contacts
STUDY_DIRECTORAbbVie
AbbVie
Participant flow
Pre-assignment details
A total of 159 participants were screened. A total of 81 participants were randomized and received at least 1 dose of study treatment. After completion of induction period, participants were eligible to enter a long-term extension period (LTE). Participants who received NX-13 250 or 750 mg during the induction period continued to receive the same blinded dose during the LTE. Participants who received placebo during the induction period were randomized to receive blinded NX-13 250 or 750 mg.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 12.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 | 0 / 15 | 0 / 36 | 0 / 32 |
| other Total, other adverse events | 12 / 33 | 8 / 33 | 4 / 15 | 10 / 36 | 5 / 32 |
| serious Total, serious adverse events | 2 / 33 | 2 / 33 | 0 / 15 | 2 / 36 | 0 / 32 |
Outcome results
None listed