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

NCT03496571 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AK002-003
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 21

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

Keywords

Eosinophilic Gastritis; Eosinophilic Gastroenteritis; Eosinophil; EG; EGE; Eosinophilic gastrointestinal disorders; EGID

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Treatment Responders

  On Days 85-99 and Day 99, respectively

• Percent Change in PRO Total Symptom Score (TSS) From Baseline

  Baseline to Days 85-99

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

1 mg/kg of AK002

EXPERIMENTAL

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

3 mg/kg of AK002

EXPERIMENTAL

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

Interventions

AK002 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).

1 mg/kg of AK002; 3 mg/kg of AK002

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 and ≤80 years at the time of signing ICF.
• 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.
• 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).
• 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).
• 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.
• If subject is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
• Able and willing to comply with all study procedures.
• 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.

You may not qualify if:

• Known hypersensitivity to any constituent of the study drug.
• Diagnosis of celiac disease or H. pylori infection as determined by screening EGD or a history of celiac disease diagnosed by prior EGD.
• Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
• Grade 2 or higher lymphopenia (\<0.8 × 109/L lymphocytes).
• Any disease or condition (medical or surgical) or cardiac abnormality, which, in the opinion of the Investigator, would place the subject at increased risk.
• 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.
• Treatment with chemotherapy or radiotherapy in the preceding 6 months.
• Treatment for a clinically significant helminthic parasitic infection within 6 months of screening and/or a positive helminthic test at screening.
• 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.
• 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.
• Known history of alcohol, drug, or other substance abuse or dependence.
• 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).
• Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
• Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.

Sponsors & Collaborators

• Allakos Inc.: lead

Study Sites (21)

Phoenician Centers for Research and Innovation

Phoenix, Arizona, 85021, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Ventura Clinical Trials

Ventura, California, 93003, United States

Location

UC Denver

Aurora, Colorado, 80045, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Advanced Research Institute

New Port Richey, Florida, 34653, United States

Location

Northwestern

Chicago, Illinois, 60611, United States

Location

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

National Institutes of Health

Bethesda, Maryland, 20892, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University of Pennsylvania, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Care Access Research

Pottsville, Pennsylvania, 17901, United States

Location

ClinSearch

Chattanooga, Tennessee, 37421, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Avant Research Associates

Austin, Texas, 78704, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• 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.

  PMID: 34089846 DERIVED

• 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.

  PMID: 33085861 DERIVED

MeSH Terms

Conditions

Eosinophilic enteropathy; Eosinophilic Esophagitis

Interventions

AK002

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Medical Information
• Organization: Allakos

medinfo@allakos.com

650-597-5002

Study Officials

• Henrik Rasmussen, MD, PhD

  Allakos Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 12, 2018
• Study Start: July 18, 2018
• Primary Completion: June 24, 2019
• Study Completion: June 24, 2019
• Last Updated: January 19, 2024
• Results First Posted: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)