Clinical Trials/NCT04322708

NCT04322708

Completed

Phase 2

A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lirentelimab (AK002) in Adult and Adolescent Patients With Active Eosinophilic Esophagitis

Allakos Inc.1 site in 1 country277 target enrollmentJuly 6, 2020

ConditionsEosinophilic Esophagitis

InterventionsPlacebo lirentelimab (AK002)

Drugslirentelimab (AK002)

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Eosinophilic Esophagitis
Sponsor: Allakos Inc.
Enrollment: 277
Locations: 1
Primary Endpoint: Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf 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 2/3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult and adolescent patients with active eosinophilic esophagitis. 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

July 6, 2020

End Date

January 18, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Allakos Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female aged ≥12 and ≤80 years at the time of signing ICF.
•Confirmed diagnosis of EoE and esophageal intraepithelial eosinophilic infiltration of ≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD without any other cause for the esophageal eosinophilia.
•History (by patient report) of an average of ≥2 episodes of dysphagia with intake of solid foods per week during the 4 weeks prior to Screening.
•Subjects must have failed or not be adequately controlled on standard of care treatments for EoE symptoms, which could include PPI, systemic or topical corticosteroids, and/or diet, among others.
•If on an allowed treatment for EoE, stable dose for at least 4 weeks prior to Screening and willingness to continue that dose for the study duration.
•If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
•Able and willing to comply with all study procedures.
•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 at any time during study participation.

Exclusion Criteria

•Concomitant EG, EoD, or eosinophilic colitis (EC).
•EG and/or EoD (≥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.
•Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute eosinophil count of \>1500 eosinophils/μL.
•History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
•Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mm upper endoscope or any critical esophageal stricture that requires dilation during screening.
•History of bleeding disorders or esophageal varices.
•History of malignancy; except carcinoma in situ, 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.
•Active Helicobacter pylori infection (as determined by central histology staining of the biopsy collected during the Screening EGD), unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
•Positive Ova and Parasite (O\&P) test at Screening, seropositive for Strongyloides stercoralis at Screening, and/or treatment for a clinically significant helminthic parasitic infection within 6 months of Screening.
•Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.

Arms & Interventions

Placebo

Subjects in this arm will receive 6 monthly doses of placebo.

Intervention: Placebo

1 mg/kg of lirentelimab (AK002)

Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) (1mg/kg).

Intervention: lirentelimab (AK002)

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 Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24

Time Frame: At Week 24

Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.

Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.

Time Frame: Baseline to Weeks 23-24

The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.

Secondary Outcomes

Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24(At Week 24)
Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24(Weeks 23-24)
Percent Change in DSQ Score From Baseline to Weeks 23-24(Baseline to Weeks 23-24)
Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24(Baseline to Week 24)
Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24(Baseline to Week 24)
Number of Treatment Responders(At Weeks 23-24 and Week 24, Respectively)
Change in Biweekly Mean DSQ Over Time Using MMRM(Baseline to Weeks 23-24)
Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24(At Week 24)