A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis (ENIGMA)
Primary Purpose
Eosinophilic Gastritis, Eosinophilic Gastroenteritis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AK002
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Eosinophilic Gastritis focused on measuring Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophil, EG, EGE, Eosinophilic gastrointestinal disorders, EGID
Eligibility Criteria
Inclusion Criteria:
- Male or female aged ≥18 and ≤80 years at the time of signing ICF.
- 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.
- 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).
- 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).
- 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.
- If subject is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
- Able and willing to comply with all study procedures.
- 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:
- Known hypersensitivity to any constituent of the study drug.
- Diagnosis of celiac disease or H. pylori infection as determined by screening EGD or a history of celiac disease diagnosed by prior EGD.
- Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
- Grade 2 or higher lymphopenia (<0.8 × 109/L lymphocytes).
- Any disease or condition (medical or surgical) or cardiac abnormality, which, in the opinion of the Investigator, would place the subject at increased risk.
- 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.
- Treatment with chemotherapy or radiotherapy in the preceding 6 months.
- Treatment for a clinically significant helminthic parasitic infection within 6 months of screening and/or a positive helminthic test at screening.
- 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.
- 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.
- Known history of alcohol, drug, or other substance abuse or dependence.
- 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).
- Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
- Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.
Sites / Locations
- Phoenician Centers for Research and Innovation
- Mayo Clinic
- Ventura Clinical Trials
- UC Denver
- Riverside Clinical Research
- Advanced Research Institute
- Northwestern
- Indiana University Health
- University of Iowa
- National Institutes of Health
- Tufts Medical Center
- Mayo Clinic
- Icahn School of Medicine at Mount Sinai
- University of North Carolina - Chapel Hill
- Cincinnati Children's Hospital
- University of Pennsylvania, Perelman Center for Advanced Medicine
- Care Access Research
- ClinSearch
- Vanderbilt University
- Avant Research Associates
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
1 mg/kg of AK002
3 mg/kg of AK002
Arm Description
Subjects in this arm will receive 4 monthly doses of placebo.
Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg
Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg
Outcomes
Primary Outcome Measures
The efficacy of AK002 in patients with Eosinophilic Gastritis (EG) and/or Eosinophilic Gastroenteritis (EGE) as estimated by number of eosinophils per high power field (HPF) in gastric and/or duodenal biopsies before and after receiving AK002 or placebo.
Secondary Outcome Measures
Changes in symptoms of EG and/or EGE in a Patient Reported Outcome (PRO) questionnaire
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03496571
Brief Title
A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
July 18, 2018 (Actual)
Primary Completion Date
June 24, 2019 (Actual)
Study Completion Date
June 24, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allakos Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Gastritis, Eosinophilic Gastroenteritis
Keywords
Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophil, EG, EGE, Eosinophilic gastrointestinal disorders, EGID
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects in this arm will receive 4 monthly doses of placebo.
Arm Title
1 mg/kg of AK002
Arm Type
Experimental
Arm Description
Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg
Arm Title
3 mg/kg of AK002
Arm Type
Experimental
Arm Description
Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg
Intervention Type
Drug
Intervention Name(s)
AK002
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
The efficacy of AK002 in patients with Eosinophilic Gastritis (EG) and/or Eosinophilic Gastroenteritis (EGE) as estimated by number of eosinophils per high power field (HPF) in gastric and/or duodenal biopsies before and after receiving AK002 or placebo.
Time Frame
Day 0 (baseline) to Day 99
Secondary Outcome Measure Information:
Title
Changes in symptoms of EG and/or EGE in a Patient Reported Outcome (PRO) questionnaire
Time Frame
Day -28 (Screening) to Day 141 (End of Study)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female aged ≥18 and ≤80 years at the time of signing ICF.
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.
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).
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).
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.
If subject is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
Able and willing to comply with all study procedures.
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:
Known hypersensitivity to any constituent of the study drug.
Diagnosis of celiac disease or H. pylori infection as determined by screening EGD or a history of celiac disease diagnosed by prior EGD.
Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
Grade 2 or higher lymphopenia (<0.8 × 109/L lymphocytes).
Any disease or condition (medical or surgical) or cardiac abnormality, which, in the opinion of the Investigator, would place the subject at increased risk.
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.
Treatment with chemotherapy or radiotherapy in the preceding 6 months.
Treatment for a clinically significant helminthic parasitic infection within 6 months of screening and/or a positive helminthic test at screening.
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.
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.
Known history of alcohol, drug, or other substance abuse or dependence.
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).
Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henrik Rasmussen, MD, PhD
Organizational Affiliation
Allakos Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Phoenician Centers for Research and Innovation
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85021
Country
United States
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Ventura Clinical Trials
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
UC Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Riverside Clinical Research
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Facility Name
Advanced Research Institute
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34653
Country
United States
Facility Name
Northwestern
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
National Institutes of Health
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Pennsylvania, Perelman Center for Advanced Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Care Access Research
City
Pottsville
State/Province
Pennsylvania
ZIP/Postal Code
17901
Country
United States
Facility Name
ClinSearch
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37421
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Avant Research Associates
City
Austin
State/Province
Texas
ZIP/Postal Code
78704
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34089846
Citation
Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, Chehade M, Peterson KA, Falk GW, Murray JA, Gehman LT, Chang AT, Singh B, Rasmussen HS, Genta RM. Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab. Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2.
Results Reference
derived
PubMed Identifier
33085861
Citation
Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, Genta RM, Leung J, Khoury P, Klion AD, Hazan S, Vaezi M, Bledsoe AC, Durrani SR, Wang C, Shaw C, Chang AT, Singh B, Kamboj AP, Rasmussen HS, Rothenberg ME, Hirano I. Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis. N Engl J Med. 2020 Oct 22;383(17):1624-1634. doi: 10.1056/NEJMoa2012047.
Results Reference
derived
Learn more about this trial
A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis
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