A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Duodenitis Who Have an Inadequate Response With, Lost Response to, or Were Intolerant to Standard Therapies

Allakos Inc.1 site in 1 country94 target enrollmentMay 20, 2021

ConditionsEosinophilic Duodenitis Eosinophilic Gastroenteritis

InterventionsAK002 Placebo

DrugsAK002

Overview

Phase: Phase 3
Intervention: AK002
Conditions: Eosinophilic Duodenitis
Sponsor: Allakos Inc.
Enrollment: 94
Locations: 1
Primary Endpoint: Proportion of Tissue Eosinophil Responders at Week 24
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

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 adult patients with active eosinophilic duodenitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.

Registry

clinicaltrials.gov

Start Date

May 20, 2021

End Date

January 9, 2023

Last Updated

2 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 3 hpf in the duodenum, as determined by central histology assessment of biopsies collected during the screening EGD + colonoscopy, 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) for at least 2 weeks of screening and a weekly average TSS of ≥10 for at least 2 weeks of screening.
•Inadequate or loss of response to, or intolerant to standard therapies for 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 prednisone within 4 weeks prior to the screening visit.
•Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the gastric mucosa as determined by central histology assessment of biopsies collected during the screening EGD.
•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 by repeat EGD (for baseline eosinophil count) prior to randomization and symptoms remain consistent.
•History of inflammatory bowel disease, other chronic inflammatory diseases in the colon (with the exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery.
•History of bleeding disorders and/or esophageal varices.
•Other causes of duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis.
•Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.

Arms & Interventions

3.0 mg/kg of Lirentelimab (AK002)

Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.

Intervention: AK002

Placebo

Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.

Intervention: Placebo

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 \<=15 cells/HPF in 3 duodenal HPFs

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 Achieving Eosinophils Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24(At Week 24)
Subjects Who Achive ≥50% Reduction in TSS From Baseline to Weeks 23-24(At Weeks 23-24)
Percent Change in Tissue Eosinophils From Baseline to Week 24(Baseline to Week 24)
Number of Treatment Responders(At Weeks 23-24 and Week 24, Respectively)
Percent Change in Weekly TSS Over Time Using MMRM(Baseline to Week 24)
Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24(At Weeks 23-24)