Trial Outcomes & Findings for A Study to Assess AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis) (NCT NCT04322604)
NCT ID: NCT04322604
Last Updated: 2024-01-02
Results Overview
A tissue eosinophil responder is defined as mean eosinophil count ≤4 cells/HPF in 5 gastric HPFs for EG only patients, ≤15 cells/HPF in 3 duodenal HPFs for EoD only patients, and ≤4 cells/HPF in 5 gastric HPFs and ≤15 cells/HPF in 3 duodenal HPFs for EG+EoD patients.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
181 participants
Primary outcome timeframe
At Week 24
Results posted on
2024-01-02
Participant Flow
Participant milestones
| Measure |
3 mg/kg of Lirentelimab (AK002)
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
Placebo
Placebo: Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
91
|
90
|
|
Overall Study
COMPLETED
|
85
|
83
|
|
Overall Study
NOT COMPLETED
|
6
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
One subject did not have the duodenal biopsy samples
Baseline characteristics by cohort
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
Total
n=180 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43 years
n=91 Participants
|
41 years
n=89 Participants
|
42 years
n=180 Participants
|
|
Age, Customized
<65 years
|
81 Participants
n=91 Participants
|
85 Participants
n=89 Participants
|
166 Participants
n=180 Participants
|
|
Age, Customized
>=65 years
|
10 Participants
n=91 Participants
|
4 Participants
n=89 Participants
|
14 Participants
n=180 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=91 Participants
|
61 Participants
n=89 Participants
|
117 Participants
n=180 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=91 Participants
|
28 Participants
n=89 Participants
|
63 Participants
n=180 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
14 Participants
n=91 Participants
|
10 Participants
n=89 Participants
|
24 Participants
n=180 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
76 Participants
n=91 Participants
|
78 Participants
n=89 Participants
|
154 Participants
n=180 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=91 Participants
|
1 Participants
n=89 Participants
|
2 Participants
n=180 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=91 Participants
|
0 Participants
n=89 Participants
|
2 Participants
n=180 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=91 Participants
|
4 Participants
n=89 Participants
|
6 Participants
n=180 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=91 Participants
|
1 Participants
n=89 Participants
|
3 Participants
n=180 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=91 Participants
|
6 Participants
n=89 Participants
|
13 Participants
n=180 Participants
|
|
Race (NIH/OMB)
White
|
75 Participants
n=91 Participants
|
78 Participants
n=89 Participants
|
153 Participants
n=180 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=91 Participants
|
0 Participants
n=89 Participants
|
2 Participants
n=180 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=91 Participants
|
0 Participants
n=89 Participants
|
1 Participants
n=180 Participants
|
|
Region of Enrollment
United States
|
91 Participants
n=91 Participants
|
89 Participants
n=89 Participants
|
180 Participants
n=180 Participants
|
|
Baseline Gastric Eosinophil Count
|
51.3 Eosinophils/HPF
STANDARD_DEVIATION 57.9 • n=91 Participants
|
37.0 Eosinophils/HPF
STANDARD_DEVIATION 30.9 • n=89 Participants
|
44.3 Eosinophils/HPF
STANDARD_DEVIATION 46.9 • n=180 Participants
|
|
Baseline Duodenal Eosinophil Count
|
42.4 Eosinophils/HPF
STANDARD_DEVIATION 19.8 • n=91 Participants • One subject did not have the duodenal biopsy samples
|
39.1 Eosinophils/HPF
STANDARD_DEVIATION 15.6 • n=88 Participants • One subject did not have the duodenal biopsy samples
|
40.7 Eosinophils/HPF
STANDARD_DEVIATION 17.9 • n=179 Participants • One subject did not have the duodenal biopsy samples
|
|
Baseline Patient Reported Outcome Total and Symptom Scores
|
29.5 Score on a scale
STANDARD_DEVIATION 11.0 • n=91 Participants
|
27.7 Score on a scale
STANDARD_DEVIATION 11.1 • n=89 Participants
|
28.6 Score on a scale
STANDARD_DEVIATION 11.0 • n=180 Participants
|
PRIMARY outcome
Timeframe: At Week 24Population: Modified Intention-to-treat
A tissue eosinophil responder is defined as mean eosinophil count ≤4 cells/HPF in 5 gastric HPFs for EG only patients, ≤15 cells/HPF in 3 duodenal HPFs for EoD only patients, and ≤4 cells/HPF in 5 gastric HPFs and ≤15 cells/HPF in 3 duodenal HPFs for EG+EoD patients.
Outcome measures
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Proportion of Tissue Eosinophil Responders at Week 24
|
77 Participants
|
4 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 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Change in PRO Total Symptom Score (TSS) From Baseline to Weeks 23-24
|
-10.0 Score on a scale
Standard Error 1.2
|
-11.5 Score on a scale
Standard Error 1.1
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Modified Intention-to-treat
Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro-duodenoscopy (EGD)
Outcome measures
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=83 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=83 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Change in Tissue Eosinophils From Baseline to Week 24
|
-61.6 Cells/HPF
Standard Deviation 46.3
|
-11.7 Cells/HPF
Standard Deviation 21.3
|
SECONDARY outcome
Timeframe: At Week 24Population: Modified Intention-to-treat
Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro-duodenoscopy (EGD)
Outcome measures
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Subjects Achieving Mean Eosinophil Count ≤1 Cell/Hpf in 5 Highest Gastric Hpf and/or Mean Eosinophil Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24
|
75 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Weeks 23-24 and at Week 24, respectivelyPopulation: Modified Intention-to-treat
Treatment responders defined by \>30% improvement in TSS at Weeks 23-24 and eosinophil count ≤4 cells/hpf in 5 gastric hpf and/or eosinophil count ≤15 cells/hpf in 3 duodenal hpf at Week 24
Outcome measures
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Number of Treatment Responders
|
39 Participants
|
3 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 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Subjects Who Achieve ≥50% Reduction in TSS From Baseline to Weeks 23-24
|
36 Participants
|
29 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 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24
|
26 Participants
|
18 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 mg/kg of Lirentelimab (AK002)
n=91 Participants
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 Participants
Placebo
Placebo: Placebo
|
|---|---|---|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 2
|
-18.2 Percentage of Change
Standard Deviation 34.1
|
-17.4 Percentage of Change
Standard Deviation 31.9
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 4
|
-17.7 Percentage of Change
Standard Deviation 34.2
|
-21.2 Percentage of Change
Standard Deviation 32.8
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 6
|
-29.8 Percentage of Change
Standard Deviation 37.2
|
-28.3 Percentage of Change
Standard Deviation 37.6
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 8
|
-29.8 Percentage of Change
Standard Deviation 40.4
|
-31.3 Percentage of Change
Standard Deviation 33.6
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 10
|
-34.6 Percentage of Change
Standard Deviation 39.7
|
-36.3 Percentage of Change
Standard Deviation 39.7
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 12
|
-33.1 Percentage of Change
Standard Deviation 39.9
|
-36.2 Percentage of Change
Standard Deviation 37.3
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 14
|
-36.3 Percentage of Change
Standard Deviation 40.2
|
-38.7 Percentage of Change
Standard Deviation 36.5
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 16
|
-33.1 Percentage of Change
Standard Deviation 40.8
|
-38.8 Percentage of Change
Standard Deviation 38.8
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 18
|
-42.6 Percentage of Change
Standard Deviation 42.3
|
-41.3 Percentage of Change
Standard Deviation 37.2
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 20
|
-42.1 Percentage of Change
Standard Deviation 37.1
|
-39.9 Percentage of Change
Standard Deviation 34.9
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 22
|
-41.7 Percentage of Change
Standard Deviation 39.8
|
-41.4 Percentage of Change
Standard Deviation 37.3
|
|
Percent Change in Weekly TSS Over Time Using MMRM
Week 24
|
-39.4 Percentage of Change
Standard Deviation 39.9
|
-38.5 Percentage of Change
Standard Deviation 37.2
|
Adverse Events
3 mg/kg of Lirentelimab (AK002)
Serious events: 7 serious events
Other events: 41 other events
Deaths: 0 deaths
Placebo
Serious events: 5 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=91 participants at risk
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 participants at risk
Placebo
Placebo: Placebo
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/91 • Baseline up to Day 225
|
1.1%
1/89 • Baseline up to Day 225
|
|
Hepatobiliary disorders
Biliary dyskinesia
|
0.00%
0/91 • Baseline up to Day 225
|
1.1%
1/89 • Baseline up to Day 225
|
|
Hepatobiliary disorders
Cholecystitis acute
|
1.1%
1/91 • Baseline up to Day 225
|
0.00%
0/89 • Baseline up to Day 225
|
|
Infections and infestations
Osteomyelitis
|
1.1%
1/91 • Baseline up to Day 225
|
0.00%
0/89 • Baseline up to Day 225
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/91 • Baseline up to Day 225
|
1.1%
1/89 • Baseline up to Day 225
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
1.1%
1/91 • Baseline up to Day 225
|
1.1%
1/89 • Baseline up to Day 225
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.1%
1/91 • Baseline up to Day 225
|
0.00%
0/89 • Baseline up to Day 225
|
|
Nervous system disorders
Lumbar radiculopathy
|
1.1%
1/91 • Baseline up to Day 225
|
0.00%
0/89 • Baseline up to Day 225
|
|
Nervous system disorders
Seizure
|
1.1%
1/91 • Baseline up to Day 225
|
0.00%
0/89 • Baseline up to Day 225
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/91 • Baseline up to Day 225
|
1.1%
1/89 • Baseline up to Day 225
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal haemorrhage
|
1.1%
1/91 • Baseline up to Day 225
|
0.00%
0/89 • Baseline up to Day 225
|
Other adverse events
| Measure |
3 mg/kg of Lirentelimab (AK002)
n=91 participants at risk
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
lirentelimab (AK002): Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
|
Placebo
n=89 participants at risk
Placebo
Placebo: Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
5.5%
5/91 • Baseline up to Day 225
|
5.6%
5/89 • Baseline up to Day 225
|
|
Gastrointestinal disorders
Nausea
|
2.2%
2/91 • Baseline up to Day 225
|
5.6%
5/89 • Baseline up to Day 225
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
3/91 • Baseline up to Day 225
|
5.6%
5/89 • Baseline up to Day 225
|
|
General disorders
Fatigue
|
5.5%
5/91 • Baseline up to Day 225
|
1.1%
1/89 • Baseline up to Day 225
|
|
Infections and infestations
Corona virus infection
|
4.4%
4/91 • Baseline up to Day 225
|
6.7%
6/89 • Baseline up to Day 225
|
|
Infections and infestations
Urinary tract infection
|
3.3%
3/91 • Baseline up to Day 225
|
5.6%
5/89 • Baseline up to Day 225
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
34.1%
31/91 • Baseline up to Day 225
|
13.5%
12/89 • Baseline up to Day 225
|
|
Investigations
Coronavirus test positive
|
3.3%
3/91 • Baseline up to Day 225
|
6.7%
6/89 • 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