Clinical trial NCT04322604: A Study to Assess AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Gastritis
Eosinophilic Duodenitis
Keywords: Eosinophil
Eosinophilic
Eosinophilic gastrointestinal disorders
EGID
EG
EGE
Eosinophilic Gastritis
Eosinophilic Gastroenteritis
Eosinophilic Duodenitis
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002), given monthly for 6 doses, in patients with moderately to severely active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) who have an inadequate response with, lost response to, or were intolerant to standard therapies


Eligibility criteria: Key Inclusion Criteria:

1. Provide written informed consent.
2. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry.
3. Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the stomach and/or ≥30 eosinophils/hpf in 3 hpf in the duodenum, as determined by central histology assessment of biopsies collected during the screening EGD.
4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
5. Patients with inadequate or loss of response to, or who were intolerant to standard therapies for EG/EoD symptoms, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
6. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.
7. Willing and able to comply with all study procedures and visit schedule including follow-up visits.
8. Female patients 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 patients 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 later menstrual period) at any time during study participation.

Key Exclusion Criteria:

1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
2. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
3. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
4. Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
5. Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
6. History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
7. History of bleeding disorders and/or esophageal varices.
8. Other causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
9. Confirmed diagnosis of Hypereosinophilic Syndrome (HES).
10. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
11. Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
12. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk.
13. History of malignancy, except carcinoma in situ, 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).
14. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
15. Positive Ova and Parasite (O\&P) test and/or seropositive for Strongyloides stercoralis.
16. 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 (4 months) of study drug administration.
17. Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved hepatitis, at screening.
18. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products).
19. Known history of alcohol, drug, or other substance abuse or dependence, considered by the Investigator to be ongoing and clinically significant.
20. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment.

Primary outcomes:
measure: Proportion of Tissue Eosinophil Responders at Week 24
timeFrame: At Week 24
measure: Change in PRO Total Symptom Score (TSS) From Baseline to Weeks 23-24
timeFrame: Baseline to Weeks 23 - 24
Secondary outcomes:
measure: Change in Tissue Eosinophils From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Subjects Achieving Mean Eosinophil Count ≤1 Cell/Hpf in 5 Highest Gastric Hpf and/or Mean Eosinophil Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24
timeFrame: At Week 24
measure: Number of Treatment Responders
timeFrame: Weeks 23-24 and at Week 24, respectively
measure: Subjects Who Achieve ≥50% Reduction in TSS From Baseline to Weeks 23-24
timeFrame: At Weeks 23-24
measure: Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24
timeFrame: At Weeks 23-24
measure: Percent Change in Weekly TSS Over Time Using MMRM
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allakos Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Allakos Investigational Site
state: Alabama
city: Gilbert
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Allakos Investigational Site
state: Arkansas
city: Chula Vista
country: United States
facility: Allakos Investigational Site
state: California
city: La Jolla
country: United States
facility: Allakos Investigational Site
state: California
city: Murrieta
country: United States
facility: Allakos Investigational Site
state: California
city: Oakland
country: United States
facility: Allakos Investigational Site
state: California
city: Santa Monica
country: United States
facility: Allakos Investigational Site
state: California
city: Tustin
country: United States
facility: Allakos Investigational Site
state: California
city: Ventura
country: United States
facility: Allakos Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Allakos Investigational Site
state: California
city: Aurora
country: United States
facility: Allakos Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: Allakos Investigational Site
state: Colorado
city: Bristol
country: United States
facility: Allakos Investigational Site
state: Connecticut
city: Brandon
country: United States
facility: Allakos Investigational Site
state: Florida
city: Edgewater
country: United States
facility: Allakos Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Allakos Investigational Site
state: Florida
city: Miami
country: United States
facility: Allakos Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Allakos Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Allakos Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Allakos Investigational Site
state: Illinois
city: Crowley
country: United States
facility: Allakos Investigational Site
state: Louisiana
city: Chevy Chase
country: United States
facility: Allakos Investigational Site
state: Maryland
city: Boston
country: United States
facility: Allakos Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Allakos Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Allakos Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Allakos Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Allakos Investigational Site
state: Minnesota
city: Kansas City
country: United States
facility: Allakos Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: Allakos Investigational Site
state: Nevada
city: Reno
country: United States
facility: Allakos Investigational Site
state: Nevada
city: Great Neck
country: United States
facility: Allakos Investigational Site
state: New York
city: New York
country: United States
facility: Allakos Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Rocky Mount
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Mentor
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Allakos Investigational Site
state: Oklahoma
city: Danville
country: United States
facility: Allakos Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Allakos Investigational Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Hixson
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Allakos Investigational Site
state: Texas
city: Houston
country: United States
facility: Allakos Investigational Site
state: Texas
city: Ogden
country: United States
facility: Allakos Investigational Site
state: Utah
city: Riverton
country: United States
facility: Allakos Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Allakos Investigational Site
state: Utah
city: Sandy
country: United States
facility: Allakos Investigational Site
state: Utah
city: Fairfax
country: United States
facility: Allakos Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Allakos Investigational Site
state: Washington
Study officials:
affiliation: Allakos Inc.
name: Craig Paterson, MD
role: STUDY_DIRECTOR
References: