A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Esophagitis

Eosinophilic Esophagitis Clinical Trial

— KRYPTOS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04322708
• Other study ID #: AK002-014
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 6, 2020
• Est. completion date: January 18, 2022

Study information

• Verified date: December 2023
• Source: Allakos Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: January 18, 2022
• Est. primary completion date: June 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Other:
• Placebo
Placebo

Drug:
• lirentelimab (AK002)
Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.

Locations

Country	Name	City	State
Australia	Allakos Investigational Site	Adelaide	South Australia
Australia	Allakos Investigational Site	Box Hill	Victoria
Australia	Allakos Investigational Site	Elizabeth Vale	South Australia
Australia	Allakos Investigational Site	Prahran	Victoria
Netherlands	Allakos Investigational Site	Amsterdam	North Holland
United States	Allakos Investigational Site	Akron	Ohio
United States	Allakos Investigational Site	Ann Arbor	Michigan
United States	Allakos Investigational Site	Asheville	North Carolina
United States	Allakos Investigational Site	Atlanta	Georgia
United States	Allakos Investigational Site	Aurora	Colorado
United States	Allakos Investigational Site	Austin	Texas
United States	Allakos Investigational Site	Birmingham	Alabama
United States	Allakos Investigational Site	Boston	Massachusetts
United States	Allakos Investigational Site	Boston	Massachusetts
United States	Allakos Investigational Site	Boston	Massachusetts
United States	Allakos Investigational Site	Brandon	Florida
United States	Allakos Investigational Site	Centennial	Colorado
United States	Allakos Investigational Site	Chapel Hill	North Carolina
United States	Allakos Investigational Site	Charlotte	North Carolina
United States	Allakos Investigational Site	Charlotte	North Carolina
United States	Allakos Investigational Site	Chattanooga	Tennessee
United States	Allakos Investigational Site	Chevy Chase	Maryland
United States	Allakos Investigational Site	Chicago	Illinois
United States	Allakos Investigational Site	Cincinnati	Ohio
United States	Allakos Investigational Site	Cincinnati	Ohio
United States	Allakos Investigational Site	Cleveland	Ohio
United States	Allakos Investigational Site	Columbus	Georgia
United States	Allakos Investigational Site	Crowley	Louisiana
United States	Allakos Investigational Site	Danville	Pennsylvania
United States	Allakos Investigational Site	Dayton	Ohio
United States	Allakos Investigational Site	Durham	North Carolina
United States	Allakos Investigational Site	Edgewater	Florida
United States	Allakos Investigational Site	Garland	Texas
United States	Allakos Investigational Site	Gilbert	Arizona
United States	Allakos Investigational Site	Great Neck	New York
United States	Allakos Investigational Site	Greenville	South Carolina
United States	Allakos Investigational Site	High Point	North Carolina
United States	Allakos Investigational Site	Hixson	Tennessee
United States	Allakos Investigational Site	Huntsville	Alabama
United States	Allakos Investigational Site	Indianapolis	Indiana
United States	Allakos Investigational Site	Iowa City	Iowa
United States	Allakos Investigational Site	Jacksonville	Florida
United States	Allakos Investigational Site	Kalispell	Montana
United States	Allakos Investigational Site	Kansas City	Missouri
United States	Allakos Investigational Site	La Jolla	California
United States	Allakos Investigational Site	Las Vegas	Nevada
United States	Allakos Investigational Site	Leesburg	Virginia
United States	Allakos Investigational Site	Lexington	Kentucky
United States	Allakos Investigational Site	Little Rock	Arkansas
United States	Allakos Investigational Site	Los Angeles	California
United States	Allakos Investigational Site	Mentor	Ohio
United States	Allakos Investigational Site	Miami	Florida
United States	Allakos Investigational Site	Nashville	Tennessee
United States	Allakos Investigational Site	New York	New York
United States	Allakos Investigational Site	Oakland	California
United States	Allakos Investigational Site	Ogden	Utah
United States	Allakos Investigational Site	Oklahoma City	Oklahoma
United States	Allakos Investigational Site	Orlando	Florida
United States	Allakos Investigational Site	Orlando	Florida
United States	Allakos Investigational Site	Philadelphia	Pennsylvania
United States	Allakos Investigational Site	Phoenix	Arizona
United States	Allakos Investigational Site	Phoenix	Arizona
United States	Allakos Investigational Site	Reno	Nevada
United States	Allakos Investigational Site	Riverton	Utah
United States	Allakos Investigational Site	Rocky Mount	North Carolina
United States	Allakos Investigational Site	Salt Lake City	Utah
United States	Allakos Investigational Site	San Antonio	Texas
United States	Allakos Investigational Site	Sandy	Utah
United States	Allakos Investigational Site	Santa Monica	California
United States	Allakos Investigational Site	Scottsdale	Arizona
United States	Allakos Investigational Site	Seattle	Washington
United States	Allakos Investigational Site	Seattle	Washington
United States	Allakos Investigational Site	Tampa	Florida
United States	Allakos Investigational Site	Tampa	Florida
United States	Allakos Investigational Site	Troy	Michigan
United States	Allakos Investigational Site	Tustin	California
United States	Allakos Investigational Site	Ventura	California
United States	Allakos Investigational Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Allakos Inc.

Countries where clinical trial is conducted

United States,  Australia,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of =6 Eosinophils/Hpf at Week 24	Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.	At Week 24
Primary	Change in Dysphagia Symptom Questionnaire (DSQ) Score From 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.	Baseline to Weeks 23-24
Secondary	Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24	Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies. A greater esophageal intraepithelial eosinophil count from baseline indicates worsening disease.	Baseline to Week 24
Secondary	Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of =1 Eosinophil/Hpf at Week 24	Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.	At Week 24
Secondary	Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24	Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.	At Week 24
Secondary	Number of Treatment Responders	Treatment responders defined by >30% improvement in symptoms (DSQ) at Weeks 23-24 and peak intraepithelial eosinophilic count of =6 cells/hpf at Week 24	At Weeks 23-24 and Week 24, Respectively
Secondary	Subjects Who Achieve >50% Reduction in DSQ Score From 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.	Weeks 23-24
Secondary	Percent Change in DSQ Score From 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.	Baseline to Weeks 23-24
Secondary	Change in Biweekly Mean DSQ Over Time Using MMRM	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.	Baseline to Weeks 23-24
Secondary	Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24	EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease.	Baseline to Week 24