A Study to Assess Subcutaneous AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis

NCT05152563 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: AK002-023
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 76

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, and pharmacodynamic effect of subcutaneous lirentelimab (AK002), given monthly for 6 doses, in subjects with moderate to severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis who have an inadequate response with, lost response to, or were intolerant to standard therapies.

Conditions

Eosinophilic Gastritis; Eosinophilic Duodenitis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts.

  A responder is a subject achieving the following peak eosinophil counts: eosinophil count ≤4 cells per hpf in 5 gastric hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf

  At Week 24

• Mean absolute change in 6 symptom total symptom score (TSS: abdominal pain, nausea, abdominal cramping, loss of appetite, fullness before finishing a meal, and bloating ) as measured by the PRO questionnaire (score from 0 none - 10 worst)

  Baseline to Weeks 23 - 24

Secondary Outcomes (6)

• Percent change in tissue eosinophils

  Baseline to Week 24

• Number of treatment responders as defined by >30% improvement in symptoms and mean eosinophil count ≤4 cells/hpf in 5 gastric hpf and/or mean eosinophil count ≤15 cells/hpf in 3 duodenal hpf.

  Baseline to Weeks 23-24 and at Week 24, respectively.

• Proportion of subjects achieving mean eosinophil count ≤1 cell/hpf in 5 highest gastric hpf and mean eosinophil count ≤1 cell/hpf in 3 highest duodenal hpf

  At Week 24

• Proportion of subjects who show ≥50% reduction in TSS

  Baseline to Weeks 23-24

• Proportion of subjects who show ≥70% reduction in TSS

  Baseline to Weeks 23-24

Study Arms (4)

SC 150 mg of lirentelimab (AK002)

EXPERIMENTAL

Subjects in this arm will receive 6 monthly doses of 150 mg of lirentelimab (AK002) administered subcutaneously.

Drug: AK002

SC 300 mg of lirentelimab (AK002)

EXPERIMENTAL

Subjects in this arm will receive 6 monthly doses of 300 mg of lirentelimab (AK002) administered subcutaneously.

Drug: AK002

SC 450 mg of lirentelimab (AK002)

EXPERIMENTAL

Subjects in this arm will receive 6 monthly doses of 450 mg of lirentelimab (AK002) administered subcutaneously.

Drug: AK002

Placebo

OTHER

Placebo

Other: Placebo

Interventions

AK002 DRUG

Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8

Also known as: Lirentelimab

SC 150 mg of lirentelimab (AK002); SC 300 mg of lirentelimab (AK002); SC 450 mg of lirentelimab (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:

• Provide written informed consent.
• Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry.
• Baseline endoscopic biopsy with ≥30 eosinophils/hpf in at least 5 hpf in the stomach and/or ≥30 eosinophils/hpf in at least 3 hpf in the duodenum as determined by central histology assessment of biopsies collected during the screening EGD without any other significant cause for the eosinophilia.
• Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
• A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PRO questionnaire (score from 0-10) and a weekly average TSS of ≥10 for at least 2 weeks of screening.
• Subjects with inadequate or loss of response to, or who were intolerant to standard therapies for EG and/or EoD, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
• If subject is on preexisting dietary restrictions, willingness to maintain dietary restrictions throughout the study.
• Willing and able to comply with all study procedures and visit schedule including follow-up visits.
• Female subjects 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 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 (e.g., missed or late menstrual period) at any time during study participation.

You may not qualify if:

• Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
• Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
• Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
• Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
• Active Heliobacter pylori (H. pylori) infection as confirmed by stool antigen test for H. pylori or identified in tissue biopsies obtained at screening EGD.
• History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
• History of bleeding disorders and/or esophageal varices considered to be clinically significant by the Investigator.
• Other significant gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
• Confirmed diagnosis of hypereosinophilic syndrome (HES).
• Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
• Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
• Any disease, 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, early-stage prostate cancer, or non-melanoma skin cancers. However, subjects with cancers that have been in remission for more than 5 years and are considered cured can be enrolled.
• Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
• Positive helminthic infection on Ova and Parasite (O\&P) test.

Sponsors & Collaborators

• Allakos Inc.: lead

Study Sites (76)

Allakos Investigational Site

Birmingham, Alabama, 35205, United States

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Gilbert, Arizona, 85234, United States

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Phoenix, Arizona, 85021, United States

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Scottsdale, Arizona, 85250, United States

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Chula Vista, California, 91910, United States

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Long Beach, California, 90808, United States

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Ventura, California, 93003, United States

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Walnut Creek, California, 94598, United States

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Bristol, Connecticut, 06010, United States

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Brandon, Florida, 33511, United States

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Edgewater, Florida, 32132, United States

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Jacksonville, Florida, 32256, United States

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Kissimmee, Florida, 34741, United States

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Miami, Florida, 33125, United States

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New Port Richey, Florida, 34653, United States

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Ponte Vedra, Florida, 32081, United States

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Sunrise, Florida, 33351, United States

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Tampa, Florida, 33603, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30342, United States

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Sandy Springs, Georgia, 30328, United States

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Chicago, Illinois, 60611, United States

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Iowa City, Iowa, 52242, United States

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Kansas City, Kansas, 66160, United States

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Crowley, Louisiana, 70526, United States

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Shreveport, Louisiana, 71105, United States

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Glen Burnie, Maryland, 21061, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48104, United States

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Wyoming, Michigan, 49519, United States

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Rochester, Minnesota, 55905, United States

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Bay Saint Louis, Mississippi, 63106, United States

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Flowood, Mississippi, 39232, United States

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Kansas City, Missouri, 64108, United States

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Kalispell, Montana, 59901, United States

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Reno, Nevada, 89511, United States

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Lebanon, New Hampshire, 03756, United States

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Florham Park, New Jersey, 07932, United States

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Freehold, New Jersey, 07728, United States

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Great Neck, New York, 11023, United States

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New York, New York, 10029, United States

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Chapel Hill, North Carolina, 27599, United States

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Charlotte, North Carolina, 28204, United States

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Concord, North Carolina, 28027, United States

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Durham, North Carolina, 27710, United States

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Raleigh, North Carolina, 27607, United States

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Winston-Salem, North Carolina, 27157, United States

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Cincinnati, Ohio, 45229, United States

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Columbus, Ohio, 43210, United States

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Dayton, Ohio, 45415, United States

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Mentor, Ohio, 44060, United States

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Springboro, Ohio, 45066, United States

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Westlake, Ohio, 44145, United States

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Oklahoma City, Oklahoma, 73102, United States

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Philadelphia, Pennsylvania, 19104, United States

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Greenwood, South Carolina, 29646, United States

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Chattanooga, Tennessee, 37421, United States

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Germantown, Tennessee, 38138, United States

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Hixson, Tennessee, 37343, United States

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Nashville, Tennessee, 37212, United States

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Austin, Texas, 78757, United States

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El Paso, Texas, 79905, United States

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Fort Worth, Texas, 76104, United States

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Lubbock, Texas, 79410, United States

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San Antonio, Texas, 78229, United States

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Southlake, Texas, 76092, United States

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Webster, Texas, 77598, United States

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Wichita Falls, Texas, 76301, United States

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Ogden, Utah, 84405, United States

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Riverton, Utah, 84065, United States

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Salt Lake City, Utah, 84112, United States

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Sandy City, Utah, 84092, United States

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Fairfax, Virginia, 22031, United States

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Seattle, Washington, 98115, United States

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Allakos Investigational Site

Seattle, Washington, 98122, United States

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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

Study Officials

• Craig Paterson, MD

  Allakos Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: November 29, 2021
• First Posted: December 10, 2021
• Study Start: December 1, 2021
• Primary Completion: January 20, 2022
• Study Completion: January 20, 2022
• Last Updated: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (76)