A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis
Condition: Eosinophilic Gastritis; Eosinophilic Gastroenteritis
MeSH terms: Gastroenteritis; Gastritis; Eosinophilic Esophagitis; Enteritis; Eosinophilia
Intervention: AK002; Placebo
Intervention description: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs).; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Eosinophilic Gastritis; Eosinophilic Gastroenteritis; Eosinophil; EG; EGE; Eosinophilic gastrointestinal disorders; EGID

Summary:

      This is a Phase 2, double-blind, randomized, placebo-controlled study to assess the effects
      of AK002, given monthly for 4 doses. It is hypothesized that AK002 is more effective than
      placebo control (alternative hypothesis) in reducing the number of eosinophils per high power
      field (HPF) in gastric and/or duodenal biopsies before and after receiving AK002 or placebo
      versus no difference between AK002 and placebo control (null hypothesis).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female aged ≥18 and ≤80 years at the time of signing ICF.

          2. Average weekly score of ≥3 (on a scale from 0-10, recorded for either abdominal pain,
             diarrhea and/or nausea on the PRO questionnaire during at least 2 out of 3 weeks of
             PRO collection. A minimum of four questionnaires must be completed each qualifying
             week.

          3. Eosinophilia of the gastric mucosa ≥30 eosinophils/HPF in 5 HPFs and/or eosinophilia
             of the duodenal mucosa ≥30 eosinophils/HPF in 3 HPFs from the EGD performed during the
             screening period, without any other cause for the gastric eosinophilia (e.g.,
             parasitic or other infection or malignancy).

          4. Subjects must have failed or not be adequately controlled on standard-of-care
             treatments for EG or EGE symptoms (which could include PPIs, systemic or topical
             corticosteroids, and/or diet, among others).

          5. If on other treatments for EG, EGE, or EoE at enrollment, stable dose for at least 5
             half-lives prior to screening and willingness to continue on that dose for the
             duration of the study.

          6. If subject 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 >40
             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.

        Exclusion Criteria:

          1. Known hypersensitivity to any constituent of the study drug.

          2. Diagnosis of celiac disease or H. pylori infection as determined by screening EGD or a
             history of celiac disease diagnosed by prior EGD.

          3. Presence of abnormal laboratory values considered by the Investigator to be clinically
             significant.

          4. Grade 2 or higher lymphopenia (<0.8 × 109/L lymphocytes).

          5. Any disease or condition (medical or surgical) or cardiac abnormality, which, in the
             opinion of the Investigator, would place the subject at increased risk.

          6. History of malignancy; except carcinoma in situ in the cervix, 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.

          7. Treatment with chemotherapy or radiotherapy in the preceding 6 months.

          8. Treatment for a clinically significant helminthic parasitic infection within 6 months
             of screening and/or a positive helminthic test at screening.

          9. Use of any medications that may interfere with the study such as immunosuppressive or
             immunomodulatory drugs (including azathioprine, 6-mercaptopurine, methotrexate,
             cyclosporine, tacrolimus, anti-TNF, anti-IL-5, anti-IL-5 receptor, dupilumab, anti-IgE
             antibodies, omalizumab) or systemic corticosteroids with a daily dose >10 mg of
             prednisone or equivalent, during 5 half-lives prior to screening or during the
             screening period, except for omalizumab taken in asthma and/or urticaria patients
             where their asthma and/or urticaria cannot be controlled on other medications. In such
             cases, the dose of omalizumab should remain stable during screening and throughout the
             study.

         10. 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 of the study drug administration.

         11. Known history of alcohol, drug, or other substance abuse or dependence.

         12. 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).

         13. Women who are pregnant, breastfeeding, or planning to become pregnant while
             participating in the study.

         14. Any other reason that in the opinion of the Investigator or Medical Monitor makes the
             patient unsuitable for enrollment.