A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Duodenitis

Inclusion Criteria:

1. Provide written informed consent.
2. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent forentry.
3. Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 3 hpf in the duodenum, asdetermined by central histology assessment of biopsies collected during the screeningEGD + colonoscopy, without any other significant cause for the eosinophilia.
4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeksduring screening.
5. A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PROquestionnaire (score from 0-10) for at least 2 weeks of screening and a weekly averageTSS of ≥10 for at least 2 weeks of screening.
6. Inadequate or loss of response to, or intolerant to standard therapies for EoDsymptoms, which could include PPI, antihistamines, systemic or topicalcorticosteroids, and/or diet, among others.
7. If patient is on pre-existing dietary restrictions, willingness to maintain dietaryrestrictions throughout the study.
8. Willing and able to comply with all study procedures and visit schedule includingfollow-up visits.
9. Female patients must be either post-menopausal for at least 1 year with FSH level >30MIU/mL at screening or surgically sterile (tubal ligation, hysterectomy, or bilateraloophorectomy) for at least 3 months, or if of childbearing potential, have a negativepregnancy test and agree to use dual methods of contraception, or abstain from sexualactivity from screening until the end of the study, or for 120 days following the lastdose of study drug, whichever is longer. Male patients with female partners ofchildbearing potential must agree to use a highly effective method of contraceptionfrom screening until the end of the study or for 120 days following the last dose ofstudy drug, whichever is longer. All fertile men with female partners of childbearingpotential should be instructed to contact the Investigator immediately if they suspecttheir partner might be pregnant (e.g., missed or later menstrual period) at any timeduring study participation.

Exclusion Criteria:

1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/dayprednisone within 4 weeks prior to the screening visit.
2. Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the gastric mucosa asdetermined by central histology assessment of biopsies collected during the screeningEGD.
3. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, ordiet therapy within 4 weeks prior to the screening visit.
4. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere withthe study within 12 weeks prior to the screening visit.
5. Prior exposure to AK002 or known hypersensitivity to any constituent of the studydrug.
6. Active Helicobacter pylori infection, unless treated and confirmed to be negative byrepeat EGD (for baseline eosinophil count) prior to randomization and symptoms remainconsistent.
7. History of inflammatory bowel disease, other chronic inflammatory diseases in thecolon (with the exception of eosinophilic colitis), celiac disease, achalasia, oresophageal surgery.
8. History of bleeding disorders and/or esophageal varices.
9. Other causes of duodenal eosinophilia or eosinophilic granulomatosis withpolyangiitis.
10. Women who are pregnant, breastfeeding, or planning to become pregnant whileparticipating in the study.
11. Presence of an abnormal laboratory value considered to be clinically significant bythe Investigator.
12. Any disease, condition (medical or surgical), or cardiac abnormality, which, in theopinion of the Investigator, would place the patient at increased risk.
13. History of malignancy, except carcinoma in situ, early stage prostate cancer, ornon-melanoma skin cancers. However, patients with cancers that have been in remissionfor more than 5 years and are considered cured can be enrolled.
14. Treatment for a clinically significant helminthic parasitic infection within 6 monthsof screening.
15. Positive helminthic infection on Ova and Parasite (O&P) test.
16. Seropositive for Strongyloides stercoralis at screening.
17. Seropositive for HIV or hepatitis at screening, except for vaccinated patients orpatients with past but resolved hepatitis, at screening.
18. Vaccination with live attenuated vaccines within 30 days prior to initiation oftreatment in the study, during the treatment period, or vaccination expected within 5half-lives (4 months) of study drug administration. This exclusion criterion does notapply to all types and formulations of vaccines (including live attenuated vaccines)authorized by FDA or other regulatory authority for the prevention of COVID-19, whichmay be administered before, during, or after the study.
19. Participation in a concurrent interventional study with the last interventionoccurring within 30 days prior to study drug administration (or 90 days or 5half-lives, whichever is longer, for biologic products).
20. Known history of alcohol, drug, or other substance abuse or dependence that isconsidered by the Investigator to be ongoing and clinically significant.
21. Any other reason that in the opinion of the Investigator or the Medical Monitor makesthe patient unsuitable for enrollment.