Clinical trial NCT04322708: A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Esophagitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Eosinophilic Esophagitis
Keywords: EoE
Eosinophil
Esophagitis
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 277
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

1. Male or female aged ≥12 and ≤80 years at the time of signing ICF.
2. 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.
3. 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.
4. 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.
5. 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.
6. If patient 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 \>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.

Key Exclusion Criteria:

1. Concomitant EG, EoD, or eosinophilic colitis (EC).
2. 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.
3. 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.
4. History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
5. 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.
6. History of bleeding disorders or esophageal varices.
7. 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.
8. 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.
9. 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.
10. Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.
11. Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
12. Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.
13. Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.
14. Use of any biologics or medications that may interfere with the study, such as immunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor, e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab), anti-IL-13 (e.g., lebrikizumab), anti-IgE (e.g., omalizumab), within 12 weeks prior to Screening.
15. 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.
16. Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected ≤5 half-lives (≤4 months) following study drug administration.
17. Treatment with chemotherapy or radiotherapy in the preceding 6 months.
18. Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
19. Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk.
20. Known history of alcohol, drug, or other substance abuse or dependence.
21. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
22. Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.

Primary outcomes:
measure: Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24
timeFrame: At Week 24
measure: Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.
timeFrame: Baseline to Weeks 23-24
Secondary outcomes:
measure: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24
timeFrame: At Week 24
measure: Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24
timeFrame: At Week 24
measure: Number of Treatment Responders
timeFrame: At Weeks 23-24 and Week 24, Respectively
measure: Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24
timeFrame: Weeks 23-24
measure: Percent Change in DSQ Score From Baseline to Weeks 23-24
timeFrame: Baseline to Weeks 23-24
measure: Change in Biweekly Mean DSQ Over Time Using MMRM
timeFrame: Baseline to Weeks 23-24
measure: Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allakos Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Allakos Investigational Site
state: Alabama
city: Gilbert
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Allakos Investigational Site
state: Arkansas
city: La Jolla
country: United States
facility: Allakos Investigational Site
state: California
city: Los Angeles
country: United States
facility: Allakos Investigational Site
state: California
city: Oakland
country: United States
facility: Allakos Investigational Site
state: California
city: Santa Monica
country: United States
facility: Allakos Investigational Site
state: California
city: Tustin
country: United States
facility: Allakos Investigational Site
state: California
city: Ventura
country: United States
facility: Allakos Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Allakos Investigational Site
state: California
city: Aurora
country: United States
facility: Allakos Investigational Site
state: Colorado
city: Centennial
country: United States
facility: Allakos Investigational Site
state: Colorado
city: Brandon
country: United States
facility: Allakos Investigational Site
state: Florida
city: Edgewater
country: United States
facility: Allakos Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Allakos Investigational Site
state: Florida
city: Miami
country: United States
facility: Allakos Investigational Site
state: Florida
city: Orlando
country: United States
facility: Allakos Investigational Site
state: Florida
city: Orlando
country: United States
facility: Allakos Investigational Site
state: Florida
city: Tampa
country: United States
facility: Allakos Investigational Site
state: Florida
city: Tampa
country: United States
facility: Allakos Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Allakos Investigational Site
state: Georgia
city: Columbus
country: United States
facility: Allakos Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Allakos Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: Allakos Investigational Site
state: Indiana
city: Iowa City
country: United States
facility: Allakos Investigational Site
state: Iowa
city: Lexington
country: United States
facility: Allakos Investigational Site
state: Kentucky
city: Crowley
country: United States
facility: Allakos Investigational Site
state: Louisiana
city: Chevy Chase
country: United States
facility: Allakos Investigational Site
state: Maryland
city: Boston
country: United States
facility: Allakos Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Allakos Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Allakos Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Allakos Investigational Site
state: Michigan
city: Troy
country: United States
facility: Allakos Investigational Site
state: Michigan
city: Kansas City
country: United States
facility: Allakos Investigational Site
state: Missouri
city: Kalispell
country: United States
facility: Allakos Investigational Site
state: Montana
city: Las Vegas
country: United States
facility: Allakos Investigational Site
state: Nevada
city: Reno
country: United States
facility: Allakos Investigational Site
state: Nevada
city: Great Neck
country: United States
facility: Allakos Investigational Site
state: New York
city: New York
country: United States
facility: Allakos Investigational Site
state: New York
city: Asheville
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: High Point
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Rocky Mount
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Akron
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Mentor
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Allakos Investigational Site
state: Oklahoma
city: Danville
country: United States
facility: Allakos Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Allakos Investigational Site
state: Pennsylvania
city: Greenville
country: United States
facility: Allakos Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Hixson
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Allakos Investigational Site
state: Texas
city: Garland
country: United States
facility: Allakos Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Allakos Investigational Site
state: Texas
city: Ogden
country: United States
facility: Allakos Investigational Site
state: Utah
city: Riverton
country: United States
facility: Allakos Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Allakos Investigational Site
state: Utah
city: Sandy
country: United States
facility: Allakos Investigational Site
state: Utah
city: Leesburg
country: United States
facility: Allakos Investigational Site
state: Virginia
city: Seattle
country: United States
facility: Allakos Investigational Site
state: Washington
city: Seattle
country: United States
facility: Allakos Investigational Site
state: Washington
city: Adelaide
country: Australia
facility: Allakos Investigational Site
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Allakos Investigational Site
state: South Australia
city: Box Hill
country: Australia
facility: Allakos Investigational Site
state: Victoria
city: Prahran
country: Australia
facility: Allakos Investigational Site
state: Victoria
city: Amsterdam
country: Netherlands
facility: Allakos Investigational Site
state: North Holland
Study officials:
affiliation: Allakos Inc.
name: Craig Paterson, MD
role: STUDY_DIRECTOR
References: