A Phase 2 interventional study of LY3471851 and Placebo in Colitis, Ulcerative, sponsored by Nektar Therapeutics. Terminated at 116 sites in 22 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-09-05.
Sponsored by Nektar Therapeutics · Phase 2, Interventional, and Treatment
The reason for this study is to determine if the study drug LY3471851 is safe and effective in adult participants with active ulcerative colitis (UC). The study treatment will last about 52 weeks.
In stage 1, two doses (high and low) of LY3471851 will be compared to placebo. In stage 2, up to two additional doses (to be confirmed) of LY3471851 will be compared to placebo.
LY3471851 (NKTR-358) is a potential first-in-class therapeutic that may address an underlying immune system imbalance in people with many autoimmune conditions. It targets the interleukin (IL-2) receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells. By activating these cells, LY3471851 may act to bring the immune system back into balance.
1,073 studies on the registry are indexed under Colitis; 133 are open to participants now.
This study's enrollment of 81 is above the median of 60 across 771 interventional studies indexed under Colitis.
Browse Colitis studies →Nektar Therapeutics is the lead sponsor of 39 studies on the registry; 2 are open to participants now.
Of its 22 completed or terminated interventional studies of FDA-regulated products, 12 (55%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.
Drug: LY3471851
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.
Drug: LY3471851
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.
Drug: LY3471851 · Drug: Placebo
administered SC
Also known as: NKTR-358
administered SC
Percentage of Participants Who Achieved Clinical Remission at Week 12
Clinical remission is defined as achieving a Modified Mayo Score (MMS) sub-score for rectal bleeding=0, stool frequency=0, or stool frequency=1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability). The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
Time frame: Week 12
Percentage of Participants Who Achieved Clinical Response at Week 12
Clinical response is defined as a decrease in the MMS of ≥2 points and ≥30% decrease from baseline, and a decrease of ≥1 point in the rectal bleeding sub-score from baseline or a rectal bleeding score of 0 or 1. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
Time frame: Week 12
Percentage of Participants Who Achieved Endoscopic Remission at Week 12
Endoscopic remission is defined as achieving a MMS sub-score for endoscopy=0 or 1 (excluding friability). The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
Time frame: Week 12
Percentage of Participants Who Achieved Endoscopic Response at Week 12
Endoscopic response is defined as a decrease of ≥1 point in the MMS endoscopy sub-score from baseline. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
Time frame: Week 12
Percentage of Participants Who Achieved Symptomatic Remission at Week 12
Symptomatic remission is defined as achieving a MMS sub-score for stool frequency=0, or stool frequency=1 with a decrease of ≥1 point from baseline, and rectal bleeding =0. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
Time frame: Week 12
Percentage of Participants Who Achieved Symptomatic Response at Week 12
Symptomatic response is defined as a ≥30% decrease from baseline in the composite clinical endpoint of the sum of MMS sub-scores of stool frequency and rectal bleeding. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
Time frame: Week 12
Percentage of Participants Who Achieved Histologic Remission at Week 12
Histologic Remission is defined as Geboes score \<2 or subscores = 0 for Grade 2a, 2b, 3, 4, and 5. The Geboes score is a 7-item instrument used to identify histologic changes in UC. The 7 items are Grade 0: Architectural changes (0=No abnormality to 3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (0=No increase to 3=Marked increase); Grade 2A: lamina propria eosinophils (0=No increase to 3=Marked increase); Grade 2B: lamina propria neutrophils (0= No increase to 3=Marked increase); Grade 3: Neutrophils in epithelium (0=None to 3=\>50% crypts involved); Grade 4: Crypt destruction(0=none to 3=Unequivocal crypt destruction),and Grade 5: Erosion or ulceration:(0=No erosion, ulceration or granulation to 4=Ulcer or granulation tissue). The grade with severe histological observation is considered the Geboes score and ranges from 0 to 4, with higher scores indicating severe disease.
Time frame: Week 12
Percentage of Participants Who Achieved Histologic-Endoscopic Mucosal Healing (HEMH)
HEMH is defined as Geboes score \<2 AND endoscopic remission. Geboes score is a 7-item instrument used to identify histologic changes in UC. The 7-items are Grade 0: Architectural changes (0=No abnormality to 3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (0=No increase to 3=Marked increase); Grade 2A: lamina propria eosinophils (0=No increase to 3=Marked increase); Grade 2B: lamina propria neutrophils (0= No increase to 3=Marked increase); Grade 3: Neutrophils in epithelium (0=None to 3=\>50% crypts involved); Grade 4: Crypt destruction(0=none to 3=Unequivocal crypt destruction),and Grade 5: Erosion or ulceration:(0=No erosion, ulceration or granulation to 4=Ulcer or granulation tissue). The grade with severe histological observation is considered the Geboes score and ranges from 0 to 4, with higher scores indicating severe disease. Endoscopic remission is defined as achieving a MMS sub-score for endoscopy=0 or 1 (excluding friability).
Time frame: Week 12
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) - Total Score
IBDQ is a 32-item questionnaire that measures four aspects of participants' lives: symptoms directly related to the primary bowel disturbance (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). Responses are graded on a 7-point Likert scale, where 7 denotes "not a problem at all" and 1 denotes "a very severe problem." The responses are summed to produce a total score ranging from 32 to 224, with higher score indicating a better quality of life. LS Mean was calculated using ANCOVA (analysis of covariance) model with treatment, baseline value, previous advanced therapy failure status (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: \[4 to 6\] or \[7 to 9\]) and region (North America/Europe/Other) as fixed factors.
Time frame: Baseline, Week 12
Pharmacokinetics (PK): Trough Concentration of LY3471851 (Ctrough) at Week 12
C-trough is the concentration of drug in the blood immediately before the next dose was administered.
Time frame: Predose at week 12
The study consisted of: * a 12-week induction treatment period: participants randomly received either high dose LY3471851 or low dose LY3471851 or placebo. * a 40-week maintenance/extension treatment period (final dose at week 50 and study assessments at week 52) * (i) Week 12 responders enter the maintenance period where they continued to receive the same treatment to which they were randomly assigned. (Continued..)
| Milestone | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | High Dose LY3471851 (Maintenance Treatment Period) | Low Dose LY3471851 (Maintenance Treatment Period) | Placebo (Maintenance Treatment Period) | High Dose LY3471851 (Extension Treatment Period) | High Dose LY3471851 (Post-Treatment Follow-up Period) | Low Dose LY3471851 (Post-Treatment Follow-up Period) | Placebo (Post-Treatment Follow-up Period) |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 32 | 35 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Received at least one dose of study drug | 32 | 35 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 19 | 22 | 12 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 13 | 13 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Physician decision | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 7 | 11 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | High Dose LY3471851 (Maintenance Treatment Period) | Low Dose LY3471851 (Maintenance Treatment Period) | Placebo (Maintenance Treatment Period) | High Dose LY3471851 (Extension Treatment Period) | High Dose LY3471851 (Post-Treatment Follow-up Period) | Low Dose LY3471851 (Post-Treatment Follow-up Period) | Placebo (Post-Treatment Follow-up Period) |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 8 | 10 | 5 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 8 | 10 | 5 | 0 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 7 | 9 | 5 | 0 | 0 | 0 | 0 |
| Milestone | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | High Dose LY3471851 (Maintenance Treatment Period) | Low Dose LY3471851 (Maintenance Treatment Period) | Placebo (Maintenance Treatment Period) | High Dose LY3471851 (Extension Treatment Period) | High Dose LY3471851 (Post-Treatment Follow-up Period) | Low Dose LY3471851 (Post-Treatment Follow-up Period) | Placebo (Post-Treatment Follow-up Period) |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 26 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 26 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 18 | 0 | 0 | 0 |
| Milestone | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | High Dose LY3471851 (Maintenance Treatment Period) | Low Dose LY3471851 (Maintenance Treatment Period) | Placebo (Maintenance Treatment Period) | High Dose LY3471851 (Extension Treatment Period) | High Dose LY3471851 (Post-Treatment Follow-up Period) | Low Dose LY3471851 (Post-Treatment Follow-up Period) | Placebo (Post-Treatment Follow-up Period) |
|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25 | 30 | 11 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 25 | 30 | 11 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 18 | 26 | 11 |
Clinical remission is defined as achieving a Modified Mayo Score (MMS) sub-score for rectal bleeding=0, stool frequency=0, or stool frequency=1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability). The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Clinical Remission at Week 12 | 14.3 (0 to 32.6) | 7.1 (0 to 16.7) | 17.2 (3.5 to 31) |
Clinical response is defined as a decrease in the MMS of ≥2 points and ≥30% decrease from baseline, and a decrease of ≥1 point in the rectal bleeding sub-score from baseline or a rectal bleeding score of 0 or 1. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Clinical Response at Week 12 | 35.7 (10.6 to 60.8) | 39.3 (21.2 to 57.4) | 41.4 (23.5 to 59.3) |
Endoscopic remission is defined as achieving a MMS sub-score for endoscopy=0 or 1 (excluding friability). The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Endoscopic Remission at Week 12 | 28.6 (4.9 to 52.2) | 14.3 (1.3 to 27.2) | 24.1 (8.6 to 39.7) |
Endoscopic response is defined as a decrease of ≥1 point in the MMS endoscopy sub-score from baseline. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Endoscopic Response at Week 12 | 21.4 (0 to 42.9) | 32.1 (14.8 to 49.4) | 37.9 (20.3 to 55.6) |
Symptomatic remission is defined as achieving a MMS sub-score for stool frequency=0, or stool frequency=1 with a decrease of ≥1 point from baseline, and rectal bleeding =0. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Symptomatic Remission at Week 12 | 21.4 (0 to 42.9) | 32.1 (14.8 to 49.4) | 27.6 (11.3 to 43.9) |
Symptomatic response is defined as a ≥30% decrease from baseline in the composite clinical endpoint of the sum of MMS sub-scores of stool frequency and rectal bleeding. The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Symptomatic Response at Week 12 | 42.9 (16.9 to 68.8) | 42.9 (24.5 to 61.2) | 44.8 (26.7 to 62.9) |
Histologic Remission is defined as Geboes score \<2 or subscores = 0 for Grade 2a, 2b, 3, 4, and 5. The Geboes score is a 7-item instrument used to identify histologic changes in UC. The 7 items are Grade 0: Architectural changes (0=No abnormality to 3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (0=No increase to 3=Marked increase); Grade 2A: lamina propria eosinophils (0=No increase to 3=Marked increase); Grade 2B: lamina propria neutrophils (0= No increase to 3=Marked increase); Grade 3: Neutrophils in epithelium (0=None to 3=\>50% crypts involved); Grade 4: Crypt destruction(0=none to 3=Unequivocal crypt destruction),and Grade 5: Erosion or ulceration:(0=No erosion, ulceration or granulation to 4=Ulcer or granulation tissue). The grade with severe histological observation is considered the Geboes score and ranges from 0 to 4, with higher scores indicating severe disease.
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Histologic Remission at Week 12 | 7.1 (0.0 to 20.6) | 7.1 (0.0 to 16.7) | 10.3 (0.0 to 21.4) |
HEMH is defined as Geboes score \<2 AND endoscopic remission. Geboes score is a 7-item instrument used to identify histologic changes in UC. The 7-items are Grade 0: Architectural changes (0=No abnormality to 3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (0=No increase to 3=Marked increase); Grade 2A: lamina propria eosinophils (0=No increase to 3=Marked increase); Grade 2B: lamina propria neutrophils (0= No increase to 3=Marked increase); Grade 3: Neutrophils in epithelium (0=None to 3=\>50% crypts involved); Grade 4: Crypt destruction(0=none to 3=Unequivocal crypt destruction),and Grade 5: Erosion or ulceration:(0=No erosion, ulceration or granulation to 4=Ulcer or granulation tissue). The grade with severe histological observation is considered the Geboes score and ranges from 0 to 4, with higher scores indicating severe disease. Endoscopic remission is defined as achieving a MMS sub-score for endoscopy=0 or 1 (excluding friability).
| percentage of participants | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Percentage of Participants Who Achieved Histologic-Endoscopic Mucosal Healing (HEMH) | 0 (0 to 0) | 3.6 (0 to 10.4) | 6.9 (0 to 16.1) |
IBDQ is a 32-item questionnaire that measures four aspects of participants' lives: symptoms directly related to the primary bowel disturbance (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). Responses are graded on a 7-point Likert scale, where 7 denotes "not a problem at all" and 1 denotes "a very severe problem." The responses are summed to produce a total score ranging from 32 to 224, with higher score indicating a better quality of life. LS Mean was calculated using ANCOVA (analysis of covariance) model with treatment, baseline value, previous advanced therapy failure status (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: \[4 to 6\] or \[7 to 9\]) and region (North America/Europe/Other) as fixed factors.
| score on a scale | Placebo (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|---|
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) - Total Score | 26.71 ± 9.346 | 36.42 ± 7.640 | 25.76 ± 7.143 |
C-trough is the concentration of drug in the blood immediately before the next dose was administered.
| microgram per milliliter (µg/mL) | Low Dose LY3471851 (Induction Treatment Period) | High Dose LY3471851 (Induction Treatment Period) |
|---|---|---|
| Pharmacokinetics (PK): Trough Concentration of LY3471851 (Ctrough) at Week 12 | 91.3 ± 49 | 139 ± 105 |
Collected over Baseline to Follow-up (Up To Week 58). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| High Dose LY3471851 (Induction Treatment Period) | 0/32 (0%) | 2/32 (6.3%) | 20/32 (62.5%) |
| Low Dose LY3471851 (Induction Treatment Period) | 0/35 (0%) | 0/35 (0%) | 15/35 (42.9%) |
| Placebo (Induction Treatment Period) | 0/14 (0%) | 0/14 (0%) | 5/14 (35.7%) |
| High Dose LY3471851 (Maintenance Treatment Period) | 0/8 (0%) | 0/8 (0%) | 4/8 (50%) |
| Low Dose LY3471851 (Maintenance Treatment Period) | 0/10 (0%) | 1/10 (10%) | 6/10 (60%) |
| Placebo (Maintenance Treatment Period) | 0/5 (0%) | 0/5 (0%) | 1/5 (20%) |
| High Dose LY3471851 (Extension Treatment Period) | 0/26 (0%) | 0/26 (0%) | 5/26 (19.2%) |
| High Dose LY3471851 (Post-Treatment Follow-up Period) | 0/25 (0%) | 0/25 (0%) | 0/25 (0%) |
| Low Dose LY3471851 (Post-Treatment Follow-up Period) | 0/30 (0%) | 1/30 (3.3%) | 1/30 (3.3%) |
| Placebo (Post-Treatment Follow-up Period) | 0/11 (0%) | 0/11 (0%) | 1/11 (9.1%) |
| Event | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | High Dose LY3471851 (Maintenance Treatment Period) | Low Dose LY3471851 (Maintenance Treatment Period) | Placebo (Maintenance Treatment Period) | High Dose LY3471851 (Extension Treatment Period) | High Dose LY3471851 (Post-Treatment Follow-up Period) | Low Dose LY3471851 (Post-Treatment Follow-up Period) | Placebo (Post-Treatment Follow-up Period) |
|---|---|---|---|---|---|---|---|---|---|---|
| Vulval abscessInfections and infestations | 0/32 | 0/35 | 0/14 | 0/8 | 1/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| Lower limb fractureInjury, poisoning and procedural complications | 0/32 | 0/35 | 0/14 | 0/8 | 0/10 | 0/5 | 0/26 | 0/25 | 1/30 | 0/11 |
| ProctitisGastrointestinal disorders | 1/32 | 0/35 | 0/14 | 0/8 | 0/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| SyncopeNervous system disorders | 1/32 | 0/35 | 0/14 | 0/8 | 0/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| Event | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | High Dose LY3471851 (Maintenance Treatment Period) | Low Dose LY3471851 (Maintenance Treatment Period) | Placebo (Maintenance Treatment Period) | High Dose LY3471851 (Extension Treatment Period) | High Dose LY3471851 (Post-Treatment Follow-up Period) | Low Dose LY3471851 (Post-Treatment Follow-up Period) | Placebo (Post-Treatment Follow-up Period) |
|---|---|---|---|---|---|---|---|---|---|---|
| Injection site reactionGeneral disorders | 8/32 | 6/35 | 0/14 | 1/8 | 0/10 | 0/5 | 2/26 | 0/25 | 0/30 | 0/11 |
| PyrexiaGeneral disorders | 7/32 | 2/35 | 1/14 | 2/8 | 1/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| Covid-19Infections and infestations | 2/32 | 3/35 | 1/14 | 1/8 | 0/10 | 1/5 | 2/26 | 0/25 | 0/30 | 0/11 |
| NasopharyngitisInfections and infestations | 0/32 | 0/35 | 0/14 | 1/8 | 0/10 | 1/5 | 0/26 | 0/25 | 1/30 | 0/11 |
| TonsillitisInfections and infestations | 0/32 | 0/35 | 0/14 | 0/8 | 0/10 | 1/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| SyncopeNervous system disorders | 0/32 | 0/35 | 0/14 | 0/8 | 0/10 | 1/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| MalaiseGeneral disorders | 0/32 | 0/35 | 0/14 | 1/8 | 0/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| Injection related reactionInjury, poisoning and procedural complications | 0/32 | 0/35 | 0/14 | 1/8 | 1/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| Body temperature increasedInvestigations | 4/32 | 0/35 | 0/14 | 1/8 | 0/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
| HeadacheNervous system disorders | 4/32 | 1/35 | 0/14 | 0/8 | 0/10 | 0/5 | 0/26 | 0/25 | 0/30 | 0/11 |
All randomized participants.
| Age, Continuous(years) | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | Total |
|---|---|---|---|---|
| Mean | 39.2 ± 12.5 | 44.5 ± 13.8 | 45.7 ± 15.2 | 42.6 ± 13.7 |
| Sex: Female, Male(Participants) | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | Total |
|---|---|---|---|---|
| Female | 10 | 9 | 6 | 25 |
| Male | 22 | 26 | 8 | 56 |
| Race (NIH/OMB)(Participants) | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 5 | 4 | 2 | 11 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 2 | 0 | 0 | 2 |
| White | 25 | 31 | 12 | 68 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | High Dose LY3471851 (Induction Treatment Period) | Low Dose LY3471851 (Induction Treatment Period) | Placebo (Induction Treatment Period) | Total |
|---|---|---|---|---|
| Argentina | 2 | 1 | 1 | 4 |
| Australia | 0 | 1 | 0 | 1 |
| Belgium | 0 | 0 | 1 | 1 |
| Czechia | 2 | 4 | 0 | 6 |
| Hungary | 3 | 3 | 0 | 6 |
| Japan | 3 | 1 | 1 | 5 |
| South Korea | 1 | 3 | 1 | 5 |
| Latvia | 2 | 3 | 0 | 5 |
| Poland | 2 | 2 | 1 | 5 |
| Russia | 5 | 5 | 3 | 13 |
| Slovakia | 1 | 1 | 1 | 3 |
| Ukraine | 7 | 7 | 4 | 18 |
| United States | 3 | 4 | 1 | 8 |
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