A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis

Eosinophilic Gastroenteritis Clinical Trial

— ENIGMA  

Official title:

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03496571
• Other study ID #: AK002-003
• Status: Completed
• Phase: Phase 2
• Start date: July 18, 2018
• Est. completion date: June 24, 2019

Study information

• Verified date: January 2024
• Source: Allakos Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, double-blind, randomized, placebo-controlled study to assess the effects of AK002, given monthly for 4 doses. It is hypothesized that AK002 is more effective than placebo control (alternative hypothesis) in reducing the number of eosinophils per high power field (HPF) in gastric and/or duodenal biopsies before and after receiving AK002 or placebo versus no difference between AK002 and placebo control (null hypothesis).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: June 24, 2019
• Est. primary completion date: June 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male or female aged =18 and =80 years at the time of signing ICF.

2. Average weekly score of =3 (on a scale from 0-10, recorded for either abdominal pain, diarrhea and/or nausea on the PRO questionnaire during at least 2 out of 3 weeks of PRO collection. A minimum of four questionnaires must be completed each qualifying week.

3. Eosinophilia of the gastric mucosa =30 eosinophils/HPF in 5 HPFs and/or eosinophilia of the duodenal mucosa =30 eosinophils/HPF in 3 HPFs from the EGD performed during the screening period, without any other cause for the gastric eosinophilia (e.g., parasitic or other infection or malignancy).

4. Subjects must have failed or not be adequately controlled on standard-of-care treatments for EG or EGE symptoms (which could include PPIs, systemic or topical corticosteroids, and/or diet, among others).

5. If on other treatments for EG, EGE, or EoE at enrollment, stable dose for at least 5 half-lives prior to screening and willingness to continue on that dose for the duration of the study.

6. If subject is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.

7. Able and willing to comply with all study procedures.

8. Female subjects must be either post-menopausal for at least 1 year with FSH level >40 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 at any time during study participation.

Exclusion Criteria:

1. Known hypersensitivity to any constituent of the study drug.

2. Diagnosis of celiac disease or H. pylori infection as determined by screening EGD or a history of celiac disease diagnosed by prior EGD.

3. Presence of abnormal laboratory values considered by the Investigator to be clinically significant.

4. Grade 2 or higher lymphopenia (<0.8 × 109/L lymphocytes).

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

6. History of malignancy; except carcinoma in situ in the cervix, early stage prostate cancer, or non-melanoma skin cancers. However, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled (with the exception of breast cancer). All history of malignancy (including diagnosis, dates, and compliance with cancer screening recommendations) must be documented and certified by the Investigator, along with the statement that in their clinical judgment the tissue eosinophilia is attributable to EGID, rather than recurrence of malignancy.

7. Treatment with chemotherapy or radiotherapy in the preceding 6 months.

8. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening and/or a positive helminthic test at screening.

9. Use of any medications that may interfere with the study such as immunosuppressive or immunomodulatory drugs (including azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-5, anti-IL-5 receptor, dupilumab, anti-IgE antibodies, omalizumab) or systemic corticosteroids with a daily dose >10 mg of prednisone or equivalent, during 5 half-lives prior to screening or during the screening period, except for omalizumab taken in asthma and/or urticaria patients where their asthma and/or urticaria cannot be controlled on other medications. In such cases, the dose of omalizumab should remain stable during screening and throughout the study.

10. 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 of the study drug administration.

11. Known history of alcohol, drug, or other substance abuse or dependence.

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

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

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

Related Conditions & MeSH terms

• Enteritis
• Eosinophilia
• Eosinophilic Esophagitis
• Eosinophilic Gastritis
• Eosinophilic Gastroenteritis
• Gastritis
• Gastroenteritis

Intervention

Drug:
• AK002
AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs).

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	UC Denver	Aurora	Colorado
United States	Avant Research Associates	Austin	Texas
United States	National Institutes of Health	Bethesda	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	ClinSearch	Chattanooga	Tennessee
United States	Northwestern	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Riverside Clinical Research	Edgewater	Florida
United States	Indiana University Health	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Vanderbilt University	Nashville	Tennessee
United States	Advanced Research Institute	New Port Richey	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	University of Pennsylvania, Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Phoenician Centers for Research and Innovation	Phoenix	Arizona
United States	Care Access Research	Pottsville	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	Mayo Clinic	Scottsdale	Arizona
United States	Ventura Clinical Trials	Ventura	California

Sponsors (1)

Lead Sponsor	Collaborator
Allakos Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline	Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro- duodenoscopy (EGD)	Baseline to Day 99
Secondary	Number of Treatment Responders	Treatment Responders defined by >30% improvement in TSS and a reduction of >75% in eosinophils in gastric and/or duodenal mucosa. The eosinophil count is obtained on Day 99 and the TSS score is the average of the daily scores from Days 85-99.	On Days 85-99 and Day 99, respectively
Secondary	Percent Change in PRO Total Symptom Score (TSS) From Baseline	The PRO Total Symptom Score (TSS) is a patient-reported outcome (PRO) questionnaire comprises the following 8 symptoms: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating, and diarrhea. Individual symptom scores ranged from 0 to 10. The daily total symptom score ranged from 0 to 80, with higher scores indicating greater severity. TSS score at the End of Study is the average of the daily scores from Days 85-99.	Baseline to Days 85-99