A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis (ENIGMA)

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis

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).

Study Overview

• Status: Completed
• Conditions: Eosinophilic Gastritis; Eosinophilic Gastroenteritis
• Intervention / Treatment: Other: Placebo; Drug: AK002

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Phoenician Centers for Research and Innovation
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Ventura, California, United States, 93003
      • Ventura Clinical Trials
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UC Denver
  • Florida
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina - Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Perelman Center for Advanced Medicine
    • Pottsville, Pennsylvania, United States, 17901
      • Care Access Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University
  • Texas
    • Austin, Texas, United States, 78704
      • Avant Research Associates
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects in this arm will receive 4 monthly doses of placebo.	Other: Placebo; Placebo
Experimental: 1 mg/kg of AK002; Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg	Drug: AK002; 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).
Experimental: 3 mg/kg of AK002; Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg	Drug: AK002; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline	Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro- duodenoscopy (EGD)	Baseline to Day 99

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Responders	Treatment Responders defined by >30% improvement in TSS and a reduction of >75% in eosinophils in gastric and/or duodenal mucosa. The eosinophil count is obtained on Day 99 and the TSS score is the average of the daily scores from Days 85-99.	On Days 85-99 and Day 99, respectively
Percent Change in PRO Total Symptom Score (TSS) From Baseline	The PRO Total Symptom Score (TSS) is a patient-reported outcome (PRO) questionnaire comprises the following 8 symptoms: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating, and diarrhea. Individual symptom scores ranged from 0 to 10. The daily total symptom score ranged from 0 to 80, with higher scores indicating greater severity. TSS score at the End of Study is the average of the daily scores from Days 85-99.	Baseline to Days 85-99

Collaborators and Investigators

• Sponsor: Allakos Inc.
• Investigators: Study Director: Henrik Rasmussen, MD, PhD, Allakos Inc.

Publications and helpful links

General Publications

• Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, Chehade M, Peterson KA, Falk GW, Murray JA, Gehman LT, Chang AT, Singh B, Rasmussen HS, Genta RM. Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab. Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2.
• Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, Genta RM, Leung J, Khoury P, Klion AD, Hazan S, Vaezi M, Bledsoe AC, Durrani SR, Wang C, Shaw C, Chang AT, Singh B, Kamboj AP, Rasmussen HS, Rothenberg ME, Hirano I. Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis. N Engl J Med. 2020 Oct 22;383(17):1624-1634. doi: 10.1056/NEJMoa2012047.

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2018
• Primary Completion (Actual): June 24, 2019
• Study Completion (Actual): June 24, 2019

Study Registration Dates

• First Submitted: April 6, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Eosinophilic Gastritis; Eosinophilic Gastroenteritis; Eosinophil; EG; EGE; Eosinophilic gastrointestinal disorders; EGID
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Hypersensitivity; Esophageal Diseases; Esophagitis; Leukocyte Disorders; Gastritis; Gastroenteritis; Eosinophilic Esophagitis; Enteritis; Eosinophilia
• Other Study ID Numbers: AK002-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No