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

NCT ID: NCT03496571

Last Updated: 2024-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-18
• Study Completion Date: 2019-06-24

Brief 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).

Conditions

Eosinophilic Gastritis; Eosinophilic Gastroenteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Subjects in this arm will receive 4 monthly doses of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

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

Group Type: EXPERIMENTAL

AK002

Intervention Type: DRUG

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).

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

Group Type: EXPERIMENTAL

AK002

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allakos Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henrik Rasmussen, MD, PhD

Role: STUDY_DIRECTOR

Allakos Inc.

Locations

Phoenician Centers for Research and Innovation

Phoenix, Arizona, United States

Mayo Clinic

Scottsdale, Arizona, United States

Ventura Clinical Trials

Ventura, California, United States

UC Denver

Aurora, Colorado, United States

Riverside Clinical Research

Edgewater, Florida, United States

Advanced Research Institute

New Port Richey, Florida, United States

Northwestern

Chicago, Illinois, United States

Indiana University Health

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

National Institutes of Health

Bethesda, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

University of Pennsylvania, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Care Access Research

Pottsville, Pennsylvania, United States

ClinSearch

Chattanooga, Tennessee, United States

Vanderbilt University

Nashville, Tennessee, United States

Avant Research Associates

Austin, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34089846 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33085861 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AK002-003

Identifier Type: -

Identifier Source: org_study_id