Eosinophilic GastritisPhase 2ENIGMANCT03496571
A Study of AK002 in Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis
A Phase 2 study testing AK002 in people with Eosinophilic Gastritis and Eosinophilic Gastroenteritis, run by Allakos Inc. at 21 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Eosinophilic Gastritis, Eosinophilic Gastroenteritis
- What is being tested?
- AK002
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 21 sitesUnited States
- Study dates
- 18 Jul 2018to 24 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
UC Denver
Aurora, Colorado, 80045
Avant Research Associates
Austin, Texas, 78704
National Institutes of Health
Bethesda, Maryland, 20892
Tufts Medical Center
Boston, Massachusetts, 02111
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599
ClinSearch
Chattanooga, Tennessee, 37421
Northwestern
Chicago, Illinois, 60611
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Riverside Clinical Research
Edgewater, Florida, 32132
Indiana University Health
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Vanderbilt University
Nashville, Tennessee, 37212
Advanced Research Institute
New Port Richey, Florida, 34653
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of Pennsylvania, Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
Phoenician Centers for Research and Innovation
Phoenix, Arizona, 85021
Care Access Research
Pottsville, Pennsylvania, 17901
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84132
Mayo Clinic
Scottsdale, Arizona, 85259
Ventura Clinical Trials
Ventura, California, 93003
About this study
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
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).
- Being tested
- AK002, Placebo
- Keywords
- Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophil, EG, EGE, Eosinophilic gastrointestinal disorders, EGID
- Medical subject headings
- Eosinophilic enteropathy, Eosinophilic Esophagitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK002Drug
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).
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects in this arm will receive 4 monthly doses of placebo. Receives: Other: Placebo |
| 1 mg/kg of AK002 | Experimental | 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 Receives: Drug: AK002 |
| 3 mg/kg of AK002 | Experimental | 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 Receives: Drug: AK002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline to Day 99
Secondary outcomes (2)
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.
Measured: On Days 85-99 and Day 99, respectively
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.
Measured: Baseline to Days 85-99
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2018
- Study start18 Jul 2018
- Primary completion24 Jun 2019
- Study completion24 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Eosinophilic GastritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allakos Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Henrik Rasmussen, MD, PhD, Study director, Allakos Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03496571
- Sponsor's protocol ID
- AK002-003
- Acronym
- ENIGMA
- Status last verified
- Jan 2024
- First submitted
- 6 Apr 2018
- Last updated
- 19 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fu J, Sia T, Solecki R, Mallik S, Khuda R, Headen M, Bacchus L, Zheng M, Telukunta T, Shami S, Liu S, Sureshbabu S, Love K, Roby A, McDonald P, Jiang Y, Narayanan DH, Cunningham E, Matmatte AS, Tan PE, Leung J. Clinical and histologic remission achieved with upadacitinib in a patient with refractory eosinophilic gastritis and duodenitis. J Allergy Clin Immunol Pract. 2024 Jun;12(6):1649-1651. doi: 10.1016/j.jaip.2024.02.031. Epub 2024 Feb 27. No abstract available.
PubMed 38423296Dellon 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.
PubMed 34089846Dellon 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.
PubMed 33085861
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03496571
- Acronym / sponsor ID
- ENIGMA / AK002-003
- Keywords
- Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophil, EG, EGE, Eosinophilic gastrointestinal disorders, EGID
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Allakos Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Jul 2018 (actual)
- Primary completion
- 24 Jun 2019 (actual)
- Study completion
- 24 Jun 2019 (actual)
- First posted
- 12 Apr 2018 (actual)
- Results
- Posted 17 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboSubjects in this arm will receive 4 monthly doses of placebo. |
| 1 mg/kg of AK002 | Experimental | Drug: AK002Subjects 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 |
| 3 mg/kg of AK002 | Experimental | Drug: AK002Subjects 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AK002AK002 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). | Drug | 1 mg/kg of AK002, 3 mg/kg of AK002 |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline
Time frame: Baseline to Day 99
Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro- duodenoscopy (EGD)
2 secondary outcomes
Number of Treatment Responders
Time frame: On Days 85-99 and Day 99, respectively
Percent Change in PRO Total Symptom Score (TSS) From Baseline
Time frame: Baseline to Days 85-99
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38423296Fu J, Sia T, Solecki R, Mallik S, Khuda R, Headen M, Bacchus L, Zheng M, Telukunta T, Shami S, Liu S, Sureshbabu S, Love K, Roby A, McDonald P, Jiang Y, Narayanan DH, Cunningham E, Matmatte AS, Tan PE, Leung J. Clinical and histologic remission achieved with upadacitinib in a patient with refractory eosinophilic gastritis and duodenitis. J Allergy Clin Immunol Pract. 2024 Jun;12(6):1649-1651. doi: 10.1016/j.jaip.2024.02.031. Epub 2024 Feb 27. No abstract available.
- Derived from this study: PubMed 34089846Dellon 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.
- Derived from this study: PubMed 33085861Dellon 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik Rasmussen, MD, PhD study director
Allakos Inc.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AK002 in people with Eosinophilic Gastritis and Eosinophilic Gastroenteritis, run by Allakos Inc. at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline (time frame: Baseline to Day 99). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03496571, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2024.