Clinical trial NCT05152563: A Study to Assess Subcutaneous AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis
Official title: A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of Subcutaneous AK002 in Subjects With Moderate to Severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Eosinophilic Gastritis
Eosinophilic Duodenitis
Keywords: Eosinophil
Eosinophilic
Eosinophilic gastrointestinal disorders
EGID
EG
EGE
Eosinophilic Gastritis
Eosinophilic Duodenitis
Eosinophilic Gastroenteritis
EoD
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-10
Enrollment: 0
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, 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.


Eligibility criteria: 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 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.
4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
5. 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.
6. 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.
7. If subject is on preexisting dietary restrictions, willingness to maintain dietary restrictions throughout the study.
8. Willing and able to comply with all study procedures and visit schedule including follow-up visits.
9. 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.

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 Heliobacter pylori (H. pylori) infection as confirmed by stool antigen test for H. pylori or identified in tissue biopsies obtained at screening EGD.
6. History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
7. History of bleeding disorders and/or esophageal varices considered to be clinically significant by the Investigator.
8. Other significant 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 subject at increased risk.
13. 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.
14. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
15. Positive helminthic infection on Ova and Parasite (O\&P) test.
16. Seropositive for Strongyloides stercoralis at screening.
17. Seropositive for HIV or hepatitis at screening except for vaccinated subjects or subjects with past but resolved hepatitis at screening.
18. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study or expected during the treatment period. Vaccines authorized by FDA or other regulatory authority for the prevention of COVID-19 may be administered before, during, or after this protocol as per the label. The vaccine should not be administered within 7 days prior to and within 7 days after the administration of AK002 so that the side effects caused by either of the 2 medications can be more easily determined.
19. 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).
20. Known history of alcohol, drug, or other substance abuse or dependence that is considered by the Investigator to be ongoing and clinically significant.
21. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the subject unsuitable for enrollment.

Primary outcomes:
measure: Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts.
timeFrame: At Week 24
measure: 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)
timeFrame: Baseline to Weeks 23 - 24
Secondary outcomes:
measure: Percent change in tissue eosinophils
timeFrame: Baseline to Week 24
measure: 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.
timeFrame: Baseline to Weeks 23-24 and at Week 24, respectively.
measure: 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
timeFrame: At Week 24
measure: Proportion of subjects who show ≥50% reduction in TSS
timeFrame: Baseline to Weeks 23-24
measure: Proportion of subjects who show ≥70% reduction in TSS
timeFrame: Baseline to Weeks 23-24
measure: Change in weekly TSS over time
timeFrame: Baseline to Weeks 23-24
Other outcomes:
Locations:
city: Birmingham
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: Chula Vista
country: United States
facility: Allakos Investigational Site
state: California
city: Long Beach
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: 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: Kissimmee
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: Ponte Vedra
country: United States
facility: Allakos Investigational Site
state: Florida
city: Sunrise
country: United States
facility: Allakos Investigational Site
state: Florida
city: Tampa
country: United States
facility: Allakos Investigational Site
state: Florida
city: Tampa
country: United States
facility: Allakos Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Allakos Investigational Site
state: Georgia
city: Sandy Springs
country: United States
facility: Allakos Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Allakos Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: Allakos Investigational Site
state: Iowa
city: Kansas City
country: United States
facility: Allakos Investigational Site
state: Kansas
city: Crowley
country: United States
facility: Allakos Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: Allakos Investigational Site
state: Louisiana
city: Glen Burnie
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: Ann Arbor
country: United States
facility: Allakos Investigational Site
state: Michigan
city: Wyoming
country: United States
facility: Allakos Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Allakos Investigational Site
state: Minnesota
city: Bay Saint Louis
country: United States
facility: Allakos Investigational Site
state: Mississippi
city: Flowood
country: United States
facility: Allakos Investigational Site
state: Mississippi
city: Kansas City
country: United States
facility: Allakos Investigational Site
state: Missouri
city: Kalispell
country: United States
facility: Allakos Investigational Site
state: Montana
city: Reno
country: United States
facility: Allakos Investigational Site
state: Nevada
city: Lebanon
country: United States
facility: Allakos Investigational Site
state: New Hampshire
city: Florham Park
country: United States
facility: Allakos Investigational Site
state: New Jersey
city: Freehold
country: United States
facility: Allakos Investigational Site
state: New Jersey
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: Concord
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Columbus
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: Springboro
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Westlake
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Allakos Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Allakos Investigational Site
state: Pennsylvania
city: Greenwood
country: United States
facility: Allakos Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Germantown
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Hixson
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: El Paso
country: United States
facility: Allakos Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Allakos Investigational Site
state: Texas
city: Lubbock
country: United States
facility: Allakos Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Allakos Investigational Site
state: Texas
city: Southlake
country: United States
facility: Allakos Investigational Site
state: Texas
city: Webster
country: United States
facility: Allakos Investigational Site
state: Texas
city: Wichita Falls
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: Seattle
country: United States
facility: Allakos Investigational Site
state: Washington
city: Seattle
country: United States
facility: Allakos Investigational Site
state: Washington
Study officials:
affiliation: Allakos Inc.
name: Craig Paterson, MD
role: STUDY_DIRECTOR
References: