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

NCT04856891 | Completed Phase 3 Results FDA Drug

• 1 other identifier: AK002-021
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 39

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

Keywords

Eosinophil; Eosinophilic; Eosinophilic gastrointestinal disorders; EGID; EoD

Outcome Measures

Primary Outcomes (2)

• Proportion of Tissue Eosinophil Responders at Week 24

  A tissue eosinophil responder is defined as mean eosinophil count \<=15 cells/HPF in 3 duodenal HPFs

  At Week 24

• Change in PRO Total Symptom Score (TSS) From 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.

  Baseline to Weeks 23 - 24

Secondary Outcomes (6)

• Percent Change in Tissue Eosinophils From Baseline to Week 24

  Baseline to Week 24

• Subjects Achieving Eosinophils Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24

  At Week 24

• Number of Treatment Responders

  At Weeks 23-24 and Week 24, Respectively

• Subjects Who Achive ≥50% Reduction in TSS From Baseline to Weeks 23-24

  At Weeks 23-24

• Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24

  At Weeks 23-24

Study Arms (2)

3.0 mg/kg of Lirentelimab (AK002)

EXPERIMENTAL

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

Drug: AK002

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

AK002 DRUG

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

Also known as: Lirentelimab

3.0 mg/kg of Lirentelimab (AK002)

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
• Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk.
• 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.
• Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
• Positive helminthic infection on Ova and Parasite (O\&P) test.

Sponsors & Collaborators

• Allakos Inc.: lead

Study Sites (39)

Allakos Investigational Site

Birmingham, Alabama, 35209, United States

Location

Allakos Investigational Site

Gilbert, Arizona, 85234, United States

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Allakos Investigational Site

Chula Vista, California, 91910, United States

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Allakos Investigational Site

Lomita, California, 90717, United States

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Allakos Investigational Site

Wheat Ridge, Colorado, 80033, United States

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Allakos Investigational Site

Bristol, Connecticut, 06010, United States

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Allakos Investigational Site

Hamden, Connecticut, 06518, United States

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Allakos Investigational Site

Brandon, Florida, 33511, United States

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Allakos Investigational Site

Edgewater, Florida, 32132, United States

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Allakos Investigational Site

Jacksonville, Florida, 32256, United States

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Allakos Investigational Site

Kissimmee, Florida, 34741, United States

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Allakos Investigational Site

Lakewood Rch, Florida, 34211, United States

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Allakos Investigational Site

New Port Richey, Florida, 34653, United States

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Allakos Investigational Site

Ponte Vedra, Florida, 32081, United States

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Allakos Investigational Site

Crowley, Louisiana, 70526, United States

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Allakos Investigational Site

Reno, Nevada, 89511, United States

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Allakos Investigational Site

Florham Park, New Jersey, 07932, United States

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Allakos Investigational Site

Great Neck, New York, 11023, United States

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Allakos Investigational Site

Concord, North Carolina, 28027, United States

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Allakos Investigational Site

Durham, North Carolina, 27710, United States

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Allakos Investigational Site

Cincinnati, Ohio, 45219, United States

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Allakos Investigational Site

Cincinnati, Ohio, 45231, United States

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Allakos Investigational Site

Dayton, Ohio, 45415, United States

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Allakos Investigational Site

Mentor, Ohio, 44094, United States

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Allakos Investigational Site

Greenwood, South Carolina, 29646, United States

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Allakos Investigational Site

Chattanooga, Tennessee, 37421, United States

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Allakos Investigational Site

Hermitage, Tennessee, 37076, United States

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Allakos Investigational Site

Hixson, Tennessee, 37343, United States

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Allakos Investigational Site

Austin, Texas, 78745, United States

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Allakos Investigational Site

Cedar Park, Texas, 78613, United States

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Allakos Investigational Site

Fort Worth, Texas, 76104, United States

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Allakos Investigational Site

Lubbock, Texas, 79410, United States

Location

Allakos Investigational Site

San Antonio, Texas, 78229, United States

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Allakos Investigational Site

Southlake, Texas, 76092, United States

Location

Allakos Investigational Site

Webster, Texas, 77598, United States

Location

Allakos Investigational Site

Ogden, Utah, 84405, United States

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Allakos Investigational Site

Salt Lake City, Utah, 84132, United States

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Allakos Investigational Site

Sandy City, Utah, 84092, United States

Location

Allakos Investigational Site

Fredericksburg, Virginia, 22401, United States

Location

MeSH Terms

Conditions

Eosinophilic enteropathy; Eosinophilic Esophagitis

Interventions

AK002

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Medical Information
• Organization: Allakos

medinfo@allakos.com

650-597-5002

Study Officials

• Craig Paterson, MD

  Allakos Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 23, 2021
• Study Start: May 20, 2021
• Primary Completion: June 14, 2022
• Study Completion: January 9, 2023
• Last Updated: January 2, 2024
• Results First Posted: January 2, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (39)