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

NCT ID: NCT04856891

Last Updated: 2024-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-20
• Study Completion Date: 2023-01-09

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.

Conditions

Eosinophilic Duodenitis; Eosinophilic Gastroenteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

3.0 mg/kg of Lirentelimab (AK002)

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

Group Type: EXPERIMENTAL

AK002

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

AK002

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

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Other Intervention Names

Lirentelimab

Eligibility Criteria

Inclusion Criteria

1. Provide written informed consent.

2. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry.

3. 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.

4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.

5. 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.

6. 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.

7. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.

8. Willing and able to comply with all study procedures and visit schedule including follow-up visits.

9. 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

1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day prednisone within 4 weeks prior to the screening visit.

2. 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.

3. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.

4. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.

5. Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.

6. 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.

7. History of inflammatory bowel disease, other chronic inflammatory diseases in the colon (with the exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery.

8. History of bleeding disorders and/or esophageal varices.

9. Other causes of duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis.

10. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.

11. Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.

12. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk.

13. History of malignancy, except carcinoma in situ, early stage prostate cancer, or non-melanoma skin cancers. However, patients with cancers that have been in remission for more than 5 years and are considered cured can be enrolled.

14. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.

15. Positive helminthic infection on Ova and Parasite (O&P) test.

16. Seropositive for Strongyloides stercoralis at screening.

17. Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved hepatitis, at screening.

18. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration. This exclusion criterion does not apply to all types and formulations of vaccines (including live attenuated vaccines) authorized by FDA or other regulatory authority for the prevention of COVID-19, which may be administered before, during, or after the study.

19. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products).

20. Known history of alcohol, drug, or other substance abuse or dependence that is considered by the Investigator to be ongoing and clinically significant.

21. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allakos Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Paterson, MD

Role: STUDY_DIRECTOR

Allakos Inc.

Locations

Allakos Investigational Site

Birmingham, Alabama, United States

Allakos Investigational Site

Gilbert, Arizona, United States

Allakos Investigational Site

Chula Vista, California, United States

Allakos Investigational Site

Lomita, California, United States

Allakos Investigational Site

Wheat Ridge, Colorado, United States

Allakos Investigational Site

Bristol, Connecticut, United States

Allakos Investigational Site

Hamden, Connecticut, United States

Allakos Investigational Site

Brandon, Florida, United States

Allakos Investigational Site

Edgewater, Florida, United States

Allakos Investigational Site

Jacksonville, Florida, United States

Allakos Investigational Site

Kissimmee, Florida, United States

Allakos Investigational Site

Lakewood Rch, Florida, United States

Allakos Investigational Site

New Port Richey, Florida, United States

Allakos Investigational Site

Ponte Vedra, Florida, United States

Allakos Investigational Site

Crowley, Louisiana, United States

Allakos Investigational Site

Reno, Nevada, United States

Allakos Investigational Site

Florham Park, New Jersey, United States

Allakos Investigational Site

Great Neck, New York, United States

Allakos Investigational Site

Concord, North Carolina, United States

Allakos Investigational Site

Durham, North Carolina, United States

Allakos Investigational Site

Cincinnati, Ohio, United States

Allakos Investigational Site

Cincinnati, Ohio, United States

Allakos Investigational Site

Dayton, Ohio, United States

Allakos Investigational Site

Mentor, Ohio, United States

Allakos Investigational Site

Greenwood, South Carolina, United States

Allakos Investigational Site

Chattanooga, Tennessee, United States

Allakos Investigational Site

Hermitage, Tennessee, United States

Allakos Investigational Site

Hixson, Tennessee, United States

Allakos Investigational Site

Austin, Texas, United States

Allakos Investigational Site

Cedar Park, Texas, United States

Allakos Investigational Site

Fort Worth, Texas, United States

Allakos Investigational Site

Lubbock, Texas, United States

Allakos Investigational Site

San Antonio, Texas, United States

Allakos Investigational Site

Southlake, Texas, United States

Allakos Investigational Site

Webster, Texas, United States

Allakos Investigational Site

Ogden, Utah, United States

Allakos Investigational Site

Salt Lake City, Utah, United States

Allakos Investigational Site

Sandy City, Utah, United States

Allakos Investigational Site

Fredericksburg, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AK002-021

Identifier Type: -

Identifier Source: org_study_id