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

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ClinicalTrials.gov Identifier: NCT03496571
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Allakos, Inc.

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).

Condition or disease Intervention/treatment Phase
Eosinophilic Gastritis Eosinophilic Gastroenteritis Drug: AK002 Other: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : July 18, 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Subjects in this arm will receive 4 monthly doses of placebo.
Other: Placebo
Placebo

Experimental: 1 mg/kg of AK002
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
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).

Experimental: 3 mg/kg of AK002
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
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).




Primary Outcome Measures :
  1. 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 Measures :
  1. 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) ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496571


Contacts
Contact: Henrik Rasmussen, MD, PhD 443-699-5230 hrasmussen@allakos.com

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Sponsors and Collaborators
Allakos, Inc.
Investigators
Study Director: Henrik Rasmussen, MD, PhD Allakos, Inc.

Responsible Party: Allakos, Inc.
ClinicalTrials.gov Identifier: NCT03496571     History of Changes
Other Study ID Numbers: AK002-003
First Posted: April 12, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Allakos, Inc.:
Eosinophilic Gastritis
Eosinophilic Gastroenteritis
Eosinophil
EG
EGE
Eosinophilic gastrointestinal disorders
EGID

Additional relevant MeSH terms:
Gastroenteritis
Gastritis
Eosinophilic Esophagitis
Enteritis
Eosinophilia
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Esophagitis
Esophageal Diseases
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Intestinal Diseases