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

Eosinophilic Gastroenteritis Clinical Trial

— EoDyssey  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04856891
• Other study ID #: AK002-021
• Status: Completed
• Phase: Phase 3
• Start date: May 20, 2021
• Est. completion date: January 9, 2023

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: January 9, 2023
• Est. primary completion date: June 14, 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 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.

Related Conditions & MeSH terms

• Duodenitis
• Eosinophilic Duodenitis
• Eosinophilic Esophagitis
• Eosinophilic Gastroenteritis
• Gastroenteritis

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	Austin	Texas
United States	Allakos Investigational Site	Birmingham	Alabama
United States	Allakos Investigational Site	Brandon	Florida
United States	Allakos Investigational Site	Bristol	Connecticut
United States	Allakos Investigational Site	Cedar Park	Texas
United States	Allakos Investigational Site	Chattanooga	Tennessee
United States	Allakos Investigational Site	Chula Vista	California
United States	Allakos Investigational Site	Cincinnati	Ohio
United States	Allakos Investigational Site	Cincinnati	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	Florham Park	New Jersey
United States	Allakos Investigational Site	Fort Worth	Texas
United States	Allakos Investigational Site	Fredericksburg	Virginia
United States	Allakos Investigational Site	Gilbert	Arizona
United States	Allakos Investigational Site	Great Neck	New York
United States	Allakos Investigational Site	Greenwood	South Carolina
United States	Allakos Investigational Site	Hamden	Connecticut
United States	Allakos Investigational Site	Hermitage	Tennessee
United States	Allakos Investigational Site	Hixson	Tennessee
United States	Allakos Investigational Site	Jacksonville	Florida
United States	Allakos Investigational Site	Kissimmee	Florida
United States	Allakos Investigational Site	Lakewood Ranch	Florida
United States	Allakos Investigational Site	Lomita	California
United States	Allakos Investigational Site	Lubbock	Texas
United States	Allakos Investigational Site	Mentor	Ohio
United States	Allakos Investigational Site	New Port Richey	Florida
United States	Allakos Investigational Site	Ogden	Utah
United States	Allakos Investigational Site	Ponte Vedra	Florida
United States	Allakos Investigational Site	Reno	Nevada
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	Southlake	Texas
United States	Allakos Investigational Site	Webster	Texas
United States	Allakos Investigational Site	Wheat Ridge	Colorado

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 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
Primary	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	Percent Change in Tissue Eosinophils From Baseline to Week 24	Tissue eosinophil count obtained in biopsy specimens from the duodenum using esophago-gastro-duodenoscopy (EGD)	Baseline to Week 24
Secondary	Subjects Achieving Eosinophils Count =1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24	Tissue eosinophil count obtained in biopsy specimens from the duodenum using esophago-gastro-duodenoscopy (EGD)	At Week 24
Secondary	Number of Treatment Responders	Treatment responders defined by >30% improvement in TSS and eosinophil count =15 cells per hpf in 3 duodenal hpf	At Weeks 23-24 and Week 24, Respectively
Secondary	Subjects Who Achive =50% Reduction in 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.	At Weeks 23-24
Secondary	Subjects Who Achieve =70% Reduction in 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.	At Weeks 23-24
Secondary	Percent Change in Weekly TSS Over Time Using MMRM	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 Week 24