A Study to Assess Subcutaneous AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis

Eosinophilic Gastritis Clinical Trial

— ENIGMA-SC  

Official title:

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of Subcutaneous AK002 in Subjects With Moderate to Severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05152563
• Other study ID #: AK002-023
• Status: Withdrawn
• Phase: Phase 3
• Start date: December 2021
• Est. completion date: January 20, 2022

Study information

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

Clinical Trial Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, and pharmacodynamic effect of subcutaneous lirentelimab (AK002), given monthly for 6 doses, in subjects with moderate to severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis who have an inadequate response with, lost response to, or were intolerant to standard therapies.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 20, 2022
• Est. primary completion date: January 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 at least 5 hpf in the stomach and/or =30 eosinophils/hpf in at least 3 hpf in the duodenum as determined by central histology assessment of biopsies collected during the screening EGD 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) and a weekly average TSS of =10 for at least 2 weeks of screening.

6. Subjects with inadequate or loss of response to, or who were intolerant to standard therapies for EG and/or EoD, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.

7. If subject is on preexisting 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 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 (e.g., missed or late menstrual period) at any time during study participation.

Exclusion Criteria:

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

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

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

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

5. Active Heliobacter pylori (H. pylori) infection as confirmed by stool antigen test for H. pylori or identified in tissue biopsies obtained at screening EGD.

6. History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.

7. History of bleeding disorders and/or esophageal varices considered to be clinically significant by the Investigator.

8. Other significant gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).

9. Confirmed diagnosis of hypereosinophilic syndrome (HES).

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 subject at increased risk.

13. History of malignancy, except carcinoma in situ, early-stage prostate cancer, or non-melanoma skin cancers. However, subjects 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 subjects or subjects with past but resolved hepatitis at screening.

18. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study or expected during the treatment period. Vaccines authorized by FDA or other regulatory authority for the prevention of COVID-19 may be administered before, during, or after this protocol as per the label. The vaccine should not be administered within 7 days prior to and within 7 days after the administration of AK002 so that the side effects caused by either of the 2 medications can be more easily determined.

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 subject unsuitable for enrollment.

Related Conditions & MeSH terms

• Duodenitis
• Enteritis
• Eosinophilia
• Eosinophilic Duodenitis
• Eosinophilic Esophagitis
• Eosinophilic Gastritis
• Gastritis

Intervention

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

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Allakos Investigational Site	Ann Arbor	Michigan
United States	Allakos Investigational Site	Atlanta	Georgia
United States	Allakos Investigational Site	Austin	Texas
United States	Allakos Investigational Site	Bay Saint Louis	Mississippi
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	Brandon	Florida
United States	Allakos Investigational Site	Bristol	Connecticut
United States	Allakos Investigational Site	Chapel Hill	North Carolina
United States	Allakos Investigational Site	Charlotte	North Carolina
United States	Allakos Investigational Site	Chattanooga	Tennessee
United States	Allakos Investigational Site	Chicago	Illinois
United States	Allakos Investigational Site	Chula Vista	California
United States	Allakos Investigational Site	Cincinnati	Ohio
United States	Allakos Investigational Site	Columbus	Ohio
United States	Allakos Investigational Site	Concord	North Carolina
United States	Allakos Investigational Site	Crowley	Louisiana
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	El Paso	Texas
United States	Allakos Investigational Site	Fairfax	Virginia
United States	Allakos Investigational Site	Florham Park	New Jersey
United States	Allakos Investigational Site	Flowood	Mississippi
United States	Allakos Investigational Site	Fort Worth	Texas
United States	Allakos Investigational Site	Freehold	New Jersey
United States	Allakos Investigational Site	Germantown	Tennessee
United States	Allakos Investigational Site	Gilbert	Arizona
United States	Allakos Investigational Site	Glen Burnie	Maryland
United States	Allakos Investigational Site	Great Neck	New York
United States	Allakos Investigational Site	Greenwood	South Carolina
United States	Allakos Investigational Site	Hixson	Tennessee
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	Kansas City	Kansas
United States	Allakos Investigational Site	Kissimmee	Florida
United States	Allakos Investigational Site	Lebanon	New Hampshire
United States	Allakos Investigational Site	Long Beach	California
United States	Allakos Investigational Site	Lubbock	Texas
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 Port Richey	Florida
United States	Allakos Investigational Site	New York	New York
United States	Allakos Investigational Site	Ogden	Utah
United States	Allakos Investigational Site	Oklahoma City	Oklahoma
United States	Allakos Investigational Site	Philadelphia	Pennsylvania
United States	Allakos Investigational Site	Phoenix	Arizona
United States	Allakos Investigational Site	Ponte Vedra	Florida
United States	Allakos Investigational Site	Raleigh	North Carolina
United States	Allakos Investigational Site	Reno	Nevada
United States	Allakos Investigational Site	Riverton	Utah
United States	Allakos Investigational Site	Rochester	Minnesota
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	Sandy Springs	Georgia
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	Shreveport	Louisiana
United States	Allakos Investigational Site	Southlake	Texas
United States	Allakos Investigational Site	Springboro	Ohio
United States	Allakos Investigational Site	Sunrise	Florida
United States	Allakos Investigational Site	Tampa	Florida
United States	Allakos Investigational Site	Tampa	Florida
United States	Allakos Investigational Site	Ventura	California
United States	Allakos Investigational Site	Walnut Creek	California
United States	Allakos Investigational Site	Webster	Texas
United States	Allakos Investigational Site	Westlake	Ohio
United States	Allakos Investigational Site	Wichita Falls	Texas
United States	Allakos Investigational Site	Winston-Salem	North Carolina
United States	Allakos Investigational Site	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Allakos Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts.	A responder is a subject achieving the following peak eosinophil counts: eosinophil count =4 cells per hpf in 5 gastric hpf and/or eosinophil count =15 cells per hpf in 3 duodenal hpf	At Week 24
Primary	Mean absolute change in 6 symptom total symptom score (TSS: abdominal pain, nausea, abdominal cramping, loss of appetite, fullness before finishing a meal, and bloating ) as measured by the PRO questionnaire (score from 0 none - 10 worst)		Baseline to Weeks 23 - 24
Secondary	Percent change in tissue eosinophils		Baseline to Week 24
Secondary	Number of treatment responders as defined by >30% improvement in symptoms and mean eosinophil count =4 cells/hpf in 5 gastric hpf and/or mean eosinophil count =15 cells/hpf in 3 duodenal hpf.		Baseline to Weeks 23-24 and at Week 24, respectively.
Secondary	Proportion of subjects achieving mean eosinophil count =1 cell/hpf in 5 highest gastric hpf and mean eosinophil count =1 cell/hpf in 3 highest duodenal hpf		At Week 24
Secondary	Proportion of subjects who show =50% reduction in TSS		Baseline to Weeks 23-24
Secondary	Proportion of subjects who show =70% reduction in TSS		Baseline to Weeks 23-24
Secondary	Change in weekly TSS over time		Baseline to Weeks 23-24