A Study to Assess AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)

Study Overview
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Brief Summary
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This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002), given monthly for 6 doses, in patients with moderately to severely active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) who have an inadequate response with, lost response to, or were intolerant to standard therapies

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)

Conditions
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Eosinophilic Gastritis, Eosinophilic Duodenitis

Intervention / Treatment
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* Drug: lirentelimab (AK002)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Provide written informed consent. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry. Baseline endoscopic biopsy with ≥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. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening. Patients with inadequate or loss of response to, or who were intolerant to standard therapies for EG/EoD symptoms, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study. Willing and able to comply with all study procedures and visit schedule including follow-up visits. Female patients 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 patients 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 (e.g., missed or later menstrual period) at any time during study participation. Key Exclusion Criteria: Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit. Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug. Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and symptoms remain consistent. History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery. History of bleeding disorders and/or esophageal varices. Other causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA). Confirmed diagnosis of Hypereosinophilic Syndrome (HES). Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study. Presence of an abnormal laboratory value considered to be clinically significant by the Investigator. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk. 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). Treatment for a clinically significant helminthic parasitic infection within 6 months of screening. Positive Ova and Parasite (O&P) test and/or seropositive for Strongyloides stercoralis. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration. Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved hepatitis, at screening. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products). Known history of alcohol, drug, or other substance abuse or dependence, considered by the Investigator to be ongoing and clinically significant. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo<br>|
| Experimental: 3 mg/kg of lirentelimab (AK002)<br>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. | Drug: lirentelimab (AK002)<br>* Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts | A responder is a patient achieving the following peak eosinophil counts: eosinophil count ≤4 cells per hpf in 5 gastric hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf. | At Week 24 | 
| Mean absolute change in 6 symptom total symptom score (TSS: abdominal pain, nausea, abdominal cramping, loss of appetite, fullness before finishing a meal, and bloating ) as measured by the patient reported outcome (PRO) questionnaire. |  | Baseline to Weeks 23 - 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in tissue eosinophils |  | Baseline to Week 24 | 
| Proportion of patients achieving peak gastric and/or duodenal intraepithelial eosinophil count of ≤1 eosinophils/hpf |  | At Week 24 | 
| Number of treatment responders as defined by >30% improvement in TSS and eosinophil count ≤4 cells per hpf in 5 gastric hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf. |  | Baseline to Weeks 23-24 and at Week 24, respectively. | 
| Proportion of patients who show ≥50% reduction in TSS |  | Baseline to Weeks 23-24 | 
| Proportion of patients who show ≥70% reduction in TSS |  | Baseline to Weeks 23-24 | 
| Percentage change in weekly TSS over time |  | Baseline to Weeks 23-24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGE, Eosinophil, Eosinophilic, Eosinophilic gastrointestinal disorders, EGID, EG, Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophilic Duodenitis