Clinical Trials/NCT05152563

NCT05152563

Withdrawn

Phase 3

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

Allakos Inc.1 site in 1 countryDecember 2021

ConditionsEosinophilic Gastritis Eosinophilic Duodenitis

InterventionsAK002 Placebo

DrugsAK002

Overview

Phase: Phase 3
Intervention: AK002
Conditions: Eosinophilic Gastritis
Sponsor: Allakos Inc.
Locations: 1
Primary Endpoint: Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts.
Status: Withdrawn
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 2021

End Date

January 20, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Allakos Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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.

Arms & Interventions

SC 150 mg of lirentelimab (AK002)

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

Intervention: AK002

SC 300 mg of lirentelimab (AK002)

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

Intervention: AK002

SC 450 mg of lirentelimab (AK002)

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

Intervention: AK002

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: At Week 24

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

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)

Time Frame: Baseline to Weeks 23 - 24

Secondary Outcomes

Change in weekly TSS over time(Baseline to Weeks 23-24)
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 who show ≥70% reduction in TSS(Baseline to Weeks 23-24)
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)