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)
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Eosinophilic Gastritis
- Sponsor
- Allakos Inc.
- Enrollment
- 181
- Locations
- 1
- Primary Endpoint
- Proportion of Tissue Eosinophil Responders at Week 24
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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
Investigators
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 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.
- •Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
- •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.
- •If patient is on pre-existing 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 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.
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 Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
- •History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
- •History of bleeding disorders and/or esophageal varices.
- •Other causes of 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
Placebo
Placebo
Intervention: Placebo
3 mg/kg of lirentelimab (AK002)
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
Intervention: lirentelimab (AK002)
Outcomes
Primary Outcomes
Proportion of Tissue Eosinophil Responders at Week 24
Time Frame: At Week 24
A tissue eosinophil responder is defined as mean eosinophil count ≤4 cells/HPF in 5 gastric HPFs for EG only patients, ≤15 cells/HPF in 3 duodenal HPFs for EoD only patients, and ≤4 cells/HPF in 5 gastric HPFs and ≤15 cells/HPF in 3 duodenal HPFs for EG+EoD patients.
Change in PRO Total Symptom Score (TSS) From Baseline to Weeks 23-24
Time Frame: Baseline to Weeks 23 - 24
The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less-severe symptoms.
Secondary Outcomes
- Subjects Who Achieve ≥50% Reduction in TSS From Baseline to Weeks 23-24(At Weeks 23-24)
- Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24(At Weeks 23-24)
- Percent Change in Weekly TSS Over Time Using MMRM(Baseline to Week 24)
- Number of Treatment Responders(Weeks 23-24 and at Week 24, respectively)
- 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(At Week 24)
- Change in Tissue Eosinophils From Baseline to Week 24(Baseline to Week 24)