Clinical trial NCT04856891: A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Duodenitis
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Duodenitis Who Have an Inadequate Response With, Lost Response to, or Were Intolerant to Standard Therapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Duodenitis
Eosinophilic Gastroenteritis
Keywords: Eosinophil
Eosinophilic
Eosinophilic gastrointestinal disorders
EGID
EoD
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-23
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion of Tissue Eosinophil Responders at Week 24
timeFrame: At Week 24
measure: Change in PRO Total Symptom Score (TSS) From Baseline to Weeks 23-24
timeFrame: Baseline to Weeks 23 - 24
Secondary outcomes:
measure: Percent Change in Tissue Eosinophils From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Subjects Achieving Eosinophils Count ≤1 Cell/Hpf in 3 Highest Duodenal 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 Achive ≥50% Reduction in TSS From Baseline to Weeks 23-24
timeFrame: At Weeks 23-24
measure: Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24
timeFrame: At Weeks 23-24
measure: Percent Change in Weekly TSS Over Time Using MMRM
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allakos Investigational Site
state: Alabama
city: Gilbert
country: United States
facility: Allakos Investigational Site
state: Arizona
city: Chula Vista
country: United States
facility: Allakos Investigational Site
state: California
city: Lomita
country: United States
facility: Allakos Investigational Site
state: California
city: Wheat Ridge
country: United States
facility: Allakos Investigational Site
state: Colorado
city: Bristol
country: United States
facility: Allakos Investigational Site
state: Connecticut
city: Hamden
country: United States
facility: Allakos Investigational Site
state: Connecticut
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: Kissimmee
country: United States
facility: Allakos Investigational Site
state: Florida
city: Lakewood Ranch
country: United States
facility: Allakos Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Allakos Investigational Site
state: Florida
city: Ponte Vedra
country: United States
facility: Allakos Investigational Site
state: Florida
city: Crowley
country: United States
facility: Allakos Investigational Site
state: Louisiana
city: Reno
country: United States
facility: Allakos Investigational Site
state: Nevada
city: Florham Park
country: United States
facility: Allakos Investigational Site
state: New Jersey
city: Great Neck
country: United States
facility: Allakos Investigational Site
state: New York
city: Concord
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Allakos Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Allakos Investigational Site
state: Ohio
city: Cincinnati
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: Greenwood
country: United States
facility: Allakos Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Hermitage
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Hixson
country: United States
facility: Allakos Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Allakos Investigational Site
state: Texas
city: Cedar Park
country: United States
facility: Allakos Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Allakos Investigational Site
state: Texas
city: Lubbock
country: United States
facility: Allakos Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Allakos Investigational Site
state: Texas
city: Southlake
country: United States
facility: Allakos Investigational Site
state: Texas
city: Webster
country: United States
facility: Allakos Investigational Site
state: Texas
city: Ogden
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: Fredericksburg
country: United States
facility: Allakos Investigational Site
state: Virginia
Study officials:
affiliation: Allakos Inc.
name: Craig Paterson, MD
role: STUDY_DIRECTOR
References: