Eosinophilic Esophagitis
Conditions
Keywords
EoE, Eosinophil, Esophagitis
Brief summary
This is a Phase 2/3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult and adolescent patients with active eosinophilic esophagitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.
Interventions
OTHERPlacebo
Placebo
Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
Sponsors
Allakos Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female aged ≥12 and ≤80 years at the time of signing ICF. 2. Confirmed diagnosis of EoE and esophageal intraepithelial eosinophilic infiltration of ≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD without any other cause for the esophageal eosinophilia. 3. History (by patient report) of an average of ≥2 episodes of dysphagia with intake of solid foods per week during the 4 weeks prior to Screening. 4. Subjects must have failed or not be adequately controlled on standard of care treatments for EoE symptoms, which could include PPI, systemic or topical corticosteroids, and/or diet, among others. 5. If on an allowed treatment for EoE, stable dose for at least 4 weeks prior to Screening and willingness to continue that dose for the study duration. 6. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible. 7. Able and willing to comply with all study procedures. 8. Female subjects must be either post-menopausal for at least 1 year with FSH level \>30 mIU/mL at Screening or surgically sterile (tubal ligation,hysterectomy, or bilateral oophorectomy) for at least 3 months, or if of childbearing potential, have a negative pregnancy test and agree to use dual methods of contraception, or abstain from sexual activity from screening until the end of the study, or for 120 days following the last dose of study drug, whichever is longer. Male subjects with female partners of childbearing potential must agree to use a highly effective method of contraception from Screening until the end of the study or for 120 days following the last dose of study drug,whichever is longer. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant at any time during study participation. Key
Exclusion criteria
1. Concomitant EG, EoD, or eosinophilic colitis (EC). 2. EG and/or EoD (≥30 eosinophils/hpf in 5 hpf in the stomach and/or ≥30 eosinophils/hpf in 3 hpf in the duodenum) as determined by central histology assessment of biopsies collected during the Screening EGD. 3. Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute eosinophil count of \>1500 eosinophils/μL. 4. History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery. 5. Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mm upper endoscope or any critical esophageal stricture that requires dilation during screening. 6. History of bleeding disorders or esophageal varices. 7. History of malignancy; except carcinoma in situ, early stage prostate cancer, or non-melanoma skin cancers. However, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled (with the exception of breast cancer). All history of malignancy (including diagnosis, dates, and compliance with cancer screening recommendations) must be documented and certified by the Investigator, along with the statement that in their clinical judgment the tissue eosinophilia is attributable to EGID, rather than recurrence of malignancy. 8. Active Helicobacter pylori infection (as determined by central histology staining of the biopsy collected during the Screening EGD), unless treated and confirmed to be negative prior to randomization and symptoms remain consistent. 9. Positive Ova and Parasite (O&P) test at Screening, seropositive for Strongyloides stercoralis at Screening, and/or treatment for a clinically significant helminthic parasitic infection within 6 months of Screening. 10. Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved. 11. Prior exposure to AK002 or hypersensitivity to any constituent of AK002. 12. Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening. 13. Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening. 14. Use of any biologics or medications that may interfere with the study, such as immunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor, e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab), anti-IL-13 (e.g., lebrikizumab), anti-IgE (e.g., omalizumab), within 12 weeks prior to Screening. 15. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to administration of study drug or 90 days or 5 half-lives, whichever is longer, for biologic products. 16. Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected ≤5 half-lives (≤4 months) following study drug administration. 17. Treatment with chemotherapy or radiotherapy in the preceding 6 months. 18. Presence of abnormal laboratory values considered by the Investigator to be clinically significant. 19. Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk. 20. Known history of alcohol, drug, or other substance abuse or dependence. 21. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study. 22. Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24 | At Week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies. |
| Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24. | Baseline to Weeks 23-24 | The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Responders | At Weeks 23-24 and Week 24, Respectively | Treatment responders defined by \>30% improvement in symptoms (DSQ) at Weeks 23-24 and peak intraepithelial eosinophilic count of ≤6 cells/hpf at Week 24 |
| Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24 | Baseline to Week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies. A greater esophageal intraepithelial eosinophil count from baseline indicates worsening disease. |
| Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24 | Weeks 23-24 | The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. |
| Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24 | At Week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies. |
| Change in Biweekly Mean DSQ Over Time Using MMRM | Baseline to Weeks 23-24 | The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. |
| Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24 | Baseline to Week 24 | EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease. |
| Percent Change in DSQ Score From Baseline to Weeks 23-24 | Baseline to Weeks 23-24 | The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. |
| Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24 | At Week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies. |
Countries
Australia, Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AK002 1 mg/kg Patients randomized to 1, 1, 1, 1, 1, 1 mg/kg on Days 1, 29, 57, 85, 113, 141 | 93 |
| AK002 3 mg/kg Patients randomized to 1, 3, 3, 3, 3, 3 mg/kg on Days 1, 29, 57, 85, 113, 141 | 91 |
| Placebo Patients randomized to placebo on Days, 1, 29, 57, 85, 113, 141 | 92 |
| Total | 276 |
Baseline characteristics
| Characteristic | Total | Placebo | AK002 1 mg/kg | AK002 3 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 32 years | 32 years | 34 years | 29 years |
| Age, Customized <18 years | 51 Participants | 17 Participants | 17 Participants | 17 Participants |
| Age, Customized >=18 years | 225 Participants | 75 Participants | 76 Participants | 74 Participants |
| Baseline Esophageal Eosinophil Count | 59.7 Eosinophils/HPF STANDARD_DEVIATION 33.6 | 58.8 Eosinophils/HPF STANDARD_DEVIATION 32.8 | 61.2 Eosinophils/HPF STANDARD_DEVIATION 35.3 | 58.9 Eosinophils/HPF STANDARD_DEVIATION 32.8 |
| Dysphagia Symptom Questionnaire (DSQ) Total Score | 35.3 Score on a scale STANDARD_DEVIATION 11.9 | 35.2 Score on a scale STANDARD_DEVIATION 12.1 | 36.4 Score on a scale STANDARD_DEVIATION 12 | 34.2 Score on a scale STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 9 Participants | 8 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 248 Participants | 82 Participants | 84 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 256 Participants | 84 Participants | 87 Participants | 85 Participants |
| Region of Enrollment Australia | 6 Participants | 3 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Netherlands | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 267 Participants | 88 Participants | 91 Participants | 88 Participants |
| Sex: Female, Male Female | 103 Participants | 37 Participants | 40 Participants | 26 Participants |
| Sex: Female, Male Male | 173 Participants | 55 Participants | 53 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 91 | 0 / 92 |
| other Total, other adverse events | 37 / 93 | 39 / 91 | 23 / 92 |
| serious Total, serious adverse events | 4 / 93 | 3 / 91 | 2 / 92 |
Outcome results
Primary
Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Time frame: Baseline to Weeks 23-24
Population: Modified Intention-to-treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24. | -11.9 Score on a scale | Standard Error 1.8 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24. | -17.4 Score on a scale | Standard Error 1.8 |
| Placebo | Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24. | -14.6 Score on a scale | Standard Error 1.8 |
p-value: 0.24795% CI: [-1.9, 7.3]ANCOVA
p-value: 0.237295% CI: [-7.3, 1.8]ANCOVA
Primary
Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
Time frame: At Week 24
Population: Modified Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24 | 86 Participants |
| 3 mg/kg of Lirentelimab (AK002) | Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24 | 80 Participants |
| Placebo | Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24 | 10 Participants |
p-value: <0.000195% CI: [71.5, 89]Fisher Exact
p-value: <0.000195% CI: [66.1, 85.4]Fisher Exact
Secondary
Change in Biweekly Mean DSQ Over Time Using MMRM
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Time frame: Baseline to Weeks 23-24
Population: Modified Intention-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 5-6 | -8.4 Score on a Scale | Standard Deviation 12.9 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 1-2 | -4.2 Score on a Scale | Standard Deviation 9 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 3-4 | -7.2 Score on a Scale | Standard Deviation 10.9 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 7-8 | -10 Score on a Scale | Standard Deviation 13.6 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 9-10 | -10.5 Score on a Scale | Standard Deviation 14.5 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 11-12 | -11.1 Score on a Scale | Standard Deviation 14.4 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 13-14 | -11.7 Score on a Scale | Standard Deviation 15 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 15-16 | -11.4 Score on a Scale | Standard Deviation 15.8 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 17-18 | -12.4 Score on a Scale | Standard Deviation 15.6 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 19-20 | -12.1 Score on a Scale | Standard Deviation 15.6 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 21-22 | -12.4 Score on a Scale | Standard Deviation 14.7 |
| 1 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 23-24 | -12.1 Score on a Scale | Standard Deviation 15 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 23-24 | -18.0 Score on a Scale | Standard Deviation 14.7 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 17-18 | -17.5 Score on a Scale | Standard Deviation 14.4 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 1-2 | -6.5 Score on a Scale | Standard Deviation 9.9 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 13-14 | -16.5 Score on a Scale | Standard Deviation 14.6 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 11-12 | -15.0 Score on a Scale | Standard Deviation 14 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 3-4 | -8.4 Score on a Scale | Standard Deviation 12.4 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 21-22 | -17.6 Score on a Scale | Standard Deviation 15 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 5-6 | -11.5 Score on a Scale | Standard Deviation 14.1 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 15-16 | -17.0 Score on a Scale | Standard Deviation 14.8 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 9-10 | -14.7 Score on a Scale | Standard Deviation 14.7 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 7-8 | -12.2 Score on a Scale | Standard Deviation 13.8 |
| 3 mg/kg of Lirentelimab (AK002) | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 19-20 | -17.8 Score on a Scale | Standard Deviation 14.5 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 7-8 | -12.0 Score on a Scale | Standard Deviation 14.5 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 9-10 | -13.6 Score on a Scale | Standard Deviation 13.4 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 19-20 | -14.8 Score on a Scale | Standard Deviation 17 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 11-12 | -13.3 Score on a Scale | Standard Deviation 14.7 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 13-14 | -15.0 Score on a Scale | Standard Deviation 14.4 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 15-16 | -13.5 Score on a Scale | Standard Deviation 15.6 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 21-22 | -15.7 Score on a Scale | Standard Deviation 17.1 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 1-2 | -6.2 Score on a Scale | Standard Deviation 10.1 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 17-18 | -14.4 Score on a Scale | Standard Deviation 15.8 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 3-4 | -8.1 Score on a Scale | Standard Deviation 11.3 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 5-6 | -11.7 Score on a Scale | Standard Deviation 12 |
| Placebo | Change in Biweekly Mean DSQ Over Time Using MMRM | Weeks 23-24 | -14.6 Score on a Scale | Standard Deviation 17.5 |
Comparison: Weeks 23-24 Change from Baselinep-value: 0.200795% CI: [-1.4, 6.7]Mixed Models Analysis
Comparison: Weeks 23-24 Change from Baselinep-value: 0.188995% CI: [-6.8, 1.3]Mixed Models Analysis
Secondary
Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24
EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease.
Time frame: Baseline to Week 24
Population: Modified Intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24 | -1.3 Score on a scale | Standard Deviation 3.2 |
| 3 mg/kg of Lirentelimab (AK002) | Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24 | -1.0 Score on a scale | Standard Deviation 3.9 |
| Placebo | Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24 | -1.5 Score on a scale | Standard Deviation 3.8 |
p-value: 0.49895% CI: [-1.3, 0.6]ANCOVA
p-value: 0.63995% CI: [-0.7, 1.2]ANCOVA
Secondary
Number of Treatment Responders
Treatment responders defined by \>30% improvement in symptoms (DSQ) at Weeks 23-24 and peak intraepithelial eosinophilic count of ≤6 cells/hpf at Week 24
Time frame: At Weeks 23-24 and Week 24, Respectively
Population: Modified Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Number of Treatment Responders | 42 Participants |
| 3 mg/kg of Lirentelimab (AK002) | Number of Treatment Responders | 53 Participants |
| Placebo | Number of Treatment Responders | 8 Participants |
p-value: <0.000195% CI: [22.9, 49.5]Fisher Exact
p-value: <0.000195% CI: [35.9, 61]Fisher Exact
Secondary
Percent Change in DSQ Score From Baseline to Weeks 23-24
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Time frame: Baseline to Weeks 23-24
Population: Modified Intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Percent Change in DSQ Score From Baseline to Weeks 23-24 | -36.3 Percentage of Change | Standard Deviation 51.4 |
| 3 mg/kg of Lirentelimab (AK002) | Percent Change in DSQ Score From Baseline to Weeks 23-24 | -56.2 Percentage of Change | Standard Deviation 39.8 |
| Placebo | Percent Change in DSQ Score From Baseline to Weeks 23-24 | -36.2 Percentage of Change | Standard Deviation 82.5 |
p-value: 0.950695% CI: [-18.1, 17]ANCOVA
p-value: 0.051195% CI: [-35.4, 0.1]ANCOVA
Secondary
Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies. A greater esophageal intraepithelial eosinophil count from baseline indicates worsening disease.
Time frame: Baseline to Week 24
Population: Modified Intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24 | -98.9 Percentage of Change | Standard Deviation 5.6 |
| 3 mg/kg of Lirentelimab (AK002) | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24 | -99.6 Percentage of Change | Standard Deviation 1 |
| Placebo | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24 | -3.1 Percentage of Change | Standard Deviation 76 |
p-value: <0.000195% CI: [-109, -82.4]ANCOVA
p-value: <0.000195% CI: [-110, -82.5]ANCOVA
Secondary
Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
Time frame: At Week 24
Population: Modified Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24 | 86 Participants |
| 3 mg/kg of Lirentelimab (AK002) | Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24 | 80 Participants |
| Placebo | Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24 | 14 Participants |
p-value: <0.000195% CI: [66.4, 85.5]Fisher Exact
p-value: <0.000195% CI: [61.3, 81.9]Fisher Exact
Secondary
Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
Time frame: At Week 24
Population: Modified Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24 | 82 Participants |
| 3 mg/kg of Lirentelimab (AK002) | Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24 | 77 Participants |
| Placebo | Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24 | 4 Participants |
p-value: <0.000195% CI: [74.4, 90.8]Fisher Exact
p-value: <0.000195% CI: [69.8, 87.9]Fisher Exact
Secondary
Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Time frame: Weeks 23-24
Population: Modified Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1 mg/kg of Lirentelimab (AK002) | Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24 | 40 Participants |
| 3 mg/kg of Lirentelimab (AK002) | Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24 | 48 Participants |
| Placebo | Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24 | 44 Participants |
p-value: 0.556195% CI: [-19.2, 10]Fisher Exact
p-value: 0.555495% CI: [-9.9, 19.6]Fisher Exact