A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Duodenitis
Condition: Eosinophilic Duodenitis; Eosinophilic Gastroenteritis
MeSH terms: Gastroenteritis; Eosinophilic Esophagitis; Duodenitis
Intervention: AK002; Placebo
Intervention description: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.; Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Eosinophil; Eosinophilic; Eosinophilic gastrointestinal disorders; EGID; EoD

Summary:

      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 adult patients
      with active eosinophilic duodenitis. 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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent.

          2. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for
             entry.

          3. Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 3 hpf in the duodenum, as
             determined by central histology assessment of biopsies collected during the screening
             EGD + 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 weeks
             during screening.

          5. A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PRO
             questionnaire (score from 0-10) for at least 2 weeks of screening and a weekly average
             TSS of ≥10 for at least 2 weeks of screening.

          6. Inadequate or loss of response to, or intolerant to standard therapies for EoD
             symptoms, which could include PPI, antihistamines, systemic or topical
             corticosteroids, and/or diet, among others.

          7. If patient is on pre-existing dietary restrictions, willingness to maintain dietary
             restrictions throughout the study.

          8. Willing and able to comply with all study procedures and visit schedule including
             follow-up visits.

          9. 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.

        Exclusion Criteria:

          1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day
             prednisone within 4 weeks prior to the screening visit.

          2. Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the gastric mucosa as
             determined by central histology assessment of biopsies collected during the screening
             EGD.

          3. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or
             diet therapy within 4 weeks prior to the screening visit.

          4. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with
             the study within 12 weeks prior to the screening visit.

          5. Prior exposure to AK002 or known hypersensitivity to any constituent of the study
             drug.

          6. Active Helicobacter pylori infection, unless treated and confirmed to be negative by
             repeat EGD (for baseline eosinophil count) prior to randomization and symptoms remain
             consistent.

          7. History of inflammatory bowel disease, other chronic inflammatory diseases in the
             colon (with the exception of eosinophilic colitis), celiac disease, achalasia, or
             esophageal surgery.

          8. History of bleeding disorders and/or esophageal varices.

          9. Other causes of duodenal eosinophilia or eosinophilic granulomatosis with
             polyangiitis.

         10. Women who are pregnant, breastfeeding, or planning to become pregnant while
             participating in the study.

         11. Presence of an abnormal laboratory value considered to be clinically significant by
             the Investigator.

         12. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the
             opinion of the Investigator, would place the patient at increased risk.

         13. History of malignancy, except carcinoma in situ, early stage prostate cancer, or
             non-melanoma skin cancers. However, patients with cancers that have been in remission
             for more than 5 years and are considered cured can be enrolled.

         14. Treatment for a clinically significant helminthic parasitic infection within 6 months
             of 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 or
             patients with past but resolved hepatitis, at screening.

         18. 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. This exclusion criterion does not
             apply to all types and formulations of vaccines (including live attenuated vaccines)
             authorized by FDA or other regulatory authority for the prevention of COVID-19, which
             may be administered before, during, or after the study.

         19. 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).

         20. Known history of alcohol, drug, or other substance abuse or dependence that is
             considered by the Investigator to be ongoing and clinically significant.

         21. Any other reason that in the opinion of the Investigator or the Medical Monitor makes
             the patient unsuitable for enrollment.