Trial Outcomes & Findings for A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Duodenitis (NCT NCT04856891)
NCT ID: NCT04856891
Last Updated: 2024-01-02
Results Overview
A tissue eosinophil responder is defined as mean eosinophil count \<=15 cells/HPF in 3 duodenal HPFs
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
94 participants
Primary outcome timeframe
At Week 24
Results posted on
2024-01-02
Participant Flow
Participant milestones
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
47
|
|
Overall Study
COMPLETED
|
38
|
44
|
|
Overall Study
NOT COMPLETED
|
8
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Duodenitis
Baseline characteristics by cohort
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
Total
n=93 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49 years
n=5 Participants
|
50 years
n=7 Participants
|
50 years
n=5 Participants
|
|
Age, Customized
<65 years
|
38 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
39 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
46 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
|
Baseline Duodenal Eosinophil Count
|
43.9 Eosinophils/HPF
STANDARD_DEVIATION 13.2 • n=5 Participants
|
39.0 Eosinophils/HPF
STANDARD_DEVIATION 10.2 • n=7 Participants
|
41.4 Eosinophils/HPF
STANDARD_DEVIATION 12.0 • n=5 Participants
|
|
Baseline Patient Reported Outcome Total and Symptom Scores
|
30.1 Score on a scale
STANDARD_DEVIATION 10.3 • n=5 Participants
|
26.1 Score on a scale
STANDARD_DEVIATION 9.1 • n=7 Participants
|
28.1 Score on a scale
STANDARD_DEVIATION 9.8 • n=5 Participants
|
PRIMARY outcome
Timeframe: At Week 24Population: Modified Intention-to-treat
A tissue eosinophil responder is defined as mean eosinophil count \<=15 cells/HPF in 3 duodenal HPFs
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Proportion of Tissue Eosinophil Responders at Week 24
|
38 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Baseline to Weeks 23 - 24Population: Modified Intention-to-treat
The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less- severe symptoms.
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Change in PRO Total Symptom Score (TSS) From Baseline to Weeks 23-24
|
-12.7 Score on a scale
Standard Error 1.7
|
-13.0 Score on a scale
Standard Error 1.7
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Modified Intention-to-treat
Tissue eosinophil count obtained in biopsy specimens from the duodenum using esophago-gastro-duodenoscopy (EGD)
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Percent Change in Tissue Eosinophils From Baseline to Week 24
|
-99.9 Percentage of Change
Standard Deviation 0.4
|
-24.1 Percentage of Change
Standard Deviation 30.5
|
SECONDARY outcome
Timeframe: At Week 24Population: Modified Intention-to-treat
Tissue eosinophil count obtained in biopsy specimens from the duodenum using esophago-gastro-duodenoscopy (EGD)
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Subjects Achieving Eosinophils Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24
|
37 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At Weeks 23-24 and Week 24, RespectivelyPopulation: Modified Intention-to-treat
Treatment responders defined by \>30% improvement in TSS and eosinophil count ≤15 cells per hpf in 3 duodenal hpf
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Number of Treatment Responders
|
21 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: At Weeks 23-24Population: Modified Intention-to-treat
The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less- severe symptoms.
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Subjects Who Achive ≥50% Reduction in TSS From Baseline to Weeks 23-24
|
13 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: At Weeks 23-24Population: Modified Intention-to-treat
The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less- severe symptoms.
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24
|
11 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Modified Intention-to-treat
The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less- severe symptoms.
Outcome measures
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 Participants
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 2
|
-16.5 Percentage of Change
Standard Deviation 41.8
|
-13.3 Percentage of Change
Standard Deviation 37.6
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 4
|
-22.6 Percentage of Change
Standard Deviation 34.6
|
-19.7 Percentage of Change
Standard Deviation 29.1
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 6
|
-30.4 Percentage of Change
Standard Deviation 35.4
|
-31.2 Percentage of Change
Standard Deviation 31.2
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 8
|
-31.4 Percentage of Change
Standard Deviation 37.5
|
-32.6 Percentage of Change
Standard Deviation 33.0
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 10
|
-38.0 Percentage of Change
Standard Deviation 33.1
|
-35.4 Percentage of Change
Standard Deviation 31.8
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 12
|
-40.4 Percentage of Change
Standard Deviation 33.0
|
-38.1 Percentage of Change
Standard Deviation 37.0
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 14
|
-45.0 Percentage of Change
Standard Deviation 35.6
|
-43.7 Percentage of Change
Standard Deviation 30.9
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 16
|
-47.0 Percentage of Change
Standard Deviation 35.7
|
-49.6 Percentage of Change
Standard Deviation 31.8
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 18
|
-46.4 Percentage of Change
Standard Deviation 33.7
|
-50.3 Percentage of Change
Standard Deviation 30.3
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 20
|
-46.7 Percentage of Change
Standard Deviation 36.3
|
-48.3 Percentage of Change
Standard Deviation 31.4
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 22
|
-50.7 Percentage of Change
Standard Deviation 37.2
|
-46.5 Percentage of Change
Standard Deviation 34.8
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 24
|
-46.3 Percentage of Change
Standard Deviation 37.5
|
-42.5 Percentage of Change
Standard Deviation 30.9
|
Adverse Events
3.0 mg/kg of Lirentelimab (AK002)
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 participants at risk
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 participants at risk
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
2.2%
1/46 • Baseline up to Day 225
|
0.00%
0/47 • Baseline up to Day 225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian neoplasm
|
0.00%
0/46 • Baseline up to Day 225
|
2.1%
1/47 • Baseline up to Day 225
|
|
Psychiatric disorders
Depression
|
2.2%
1/46 • Baseline up to Day 225
|
0.00%
0/47 • Baseline up to Day 225
|
Other adverse events
| Measure |
3.0 mg/kg of Lirentelimab (AK002)
n=46 participants at risk
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=47 participants at risk
Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
Placebo: Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
6.5%
3/46 • Baseline up to Day 225
|
0.00%
0/47 • Baseline up to Day 225
|
|
Gastrointestinal disorders
Diarrhea
|
2.2%
1/46 • Baseline up to Day 225
|
6.4%
3/47 • Baseline up to Day 225
|
|
Gastrointestinal disorders
Hiatus hernia
|
4.3%
2/46 • Baseline up to Day 225
|
8.5%
4/47 • Baseline up to Day 225
|
|
Infections and infestations
Corona virus infection
|
10.9%
5/46 • Baseline up to Day 225
|
8.5%
4/47 • Baseline up to Day 225
|
|
Infections and infestations
Sinusitis
|
8.7%
4/46 • Baseline up to Day 225
|
2.1%
1/47 • Baseline up to Day 225
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
19.6%
9/46 • Baseline up to Day 225
|
14.9%
7/47 • Baseline up to Day 225
|
|
Nervous system disorders
Headache
|
2.2%
1/46 • Baseline up to Day 225
|
6.4%
3/47 • Baseline up to Day 225
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Clinical Trial Agreement contains a limit on publication of results following completion of the trial. PIs are not allowed to publish results until a joint publication for the multicenter study or a set period of time. After that time, PIs may only publish results from their portion of the study.
- Publication restrictions are in place
Restriction type: OTHER