Clinical trial NCT03496571: A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Gastritis
Eosinophilic Gastroenteritis
Keywords: Eosinophilic Gastritis
Eosinophilic Gastroenteritis
Eosinophil
EG
EGE
Eosinophilic gastrointestinal disorders
EGID
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-12
Enrollment: 65
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 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).


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.

Primary outcomes:
measure: Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline
timeFrame: Baseline to Day 99
Secondary outcomes:
measure: Number of Treatment Responders
timeFrame: On Days 85-99 and Day 99, respectively
measure: Percent Change in PRO Total Symptom Score (TSS) From Baseline
timeFrame: Baseline to Days 85-99
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenician Centers for Research and Innovation
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Aurora
country: United States
facility: UC Denver
state: Colorado
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pottsville
country: United States
facility: Care Access Research
state: Pennsylvania
city: Chattanooga
country: United States
facility: ClinSearch
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: Avant Research Associates
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Allakos Inc.
name: Henrik Rasmussen, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.