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A Study to Assess AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis) (ENIGMA 2)

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ClinicalTrials.gov Identifier: NCT04322604
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
Allakos, Inc.

Brief 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 patients with moderately to severely active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) who have an inadequate response with, lost response to, or were intolerant to standard therapies

Condition or disease Intervention/treatment Phase
Eosinophilic Gastritis Eosinophilic Duodenitis Drug: lirentelimab (AK002) Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)
Actual Study Start Date : June 18, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Other: Placebo
Placebo

Experimental: 3 mg/kg of lirentelimab (AK002)
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
Drug: lirentelimab (AK002)
Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.




Primary Outcome Measures :
  1. Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts [ Time Frame: At Week 24 ]
    A responder is a patient achieving the following peak eosinophil counts: eosinophil count ≤4 cells per hpf in 5 gastric hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf.

  2. Mean absolute change in 6 symptom total symptom score (TSS: abdominal pain, nausea, abdominal cramping, loss of appetite, fullness before finishing a meal, and bloating ) as measured by the patient reported outcome (PRO) questionnaire. [ Time Frame: Baseline to Week 22 - 24 ]

Secondary Outcome Measures :
  1. Percentage change in tissue eosinophils [ Time Frame: Baseline to Week 24 ]
  2. Proportion of patients achieving peak gastric and/or duodenal intraepithelial eosinophil count of ≤1 eosinophils/hpf [ Time Frame: At Week 24 ]
  3. Number of treatment responders as defined by >30% improvement in TSS and eosinophil count ≤4 cells per hpf in 5 gastric hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf. [ Time Frame: Baseline to Week 24 and at Week 24, respectively. ]
  4. Proportion of patients who show ≥50% reduction in TSS [ Time Frame: Baseline to Weeks 22-24 ]
  5. Proportion of patients who show ≥70% reduction in TSS [ Time Frame: Baseline to Weeks 22-24 ]
  6. Percentage change in weekly TSS over time [ Time Frame: Baseline to Weeks 22-24 ]


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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

Key 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 5 hpf in the stomach and/or ≥30 eosinophils/hpf in 3 hpf in the duodenum, as determined by central histology assessment of biopsies collected during the screening EGD.
  4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
  5. Patients with inadequate or loss of response to, or who were intolerant to standard therapies for EG/EoD symptoms, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
  6. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.
  7. Willing and able to comply with all study procedures and visit schedule including follow-up visits.
  8. 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.

Key Exclusion Criteria:

  1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
  2. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
  3. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
  4. Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
  5. Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
  6. History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
  7. History of bleeding disorders and/or esophageal varices.
  8. Other causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
  9. Confirmed diagnosis of Hypereosinophilic Syndrome (HES).
  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, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled (with the exception of breast cancer).
  14. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
  15. Positive Ova and Parasite (O&P) test and/or seropositive for Strongyloides stercoralis.
  16. 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.
  17. Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved hepatitis, at screening.
  18. 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).
  19. Known history of alcohol, drug, or other substance abuse or dependence, considered by the Investigator to be ongoing and clinically significant.
  20. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment.

Information from the National Library of Medicine

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): NCT04322604


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

Locations
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Sponsors and Collaborators
Allakos, Inc.
Investigators
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Study Director: Henrik Rasmussen, MD, PhD Allakos, Inc.
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Responsible Party: Allakos, Inc.
ClinicalTrials.gov Identifier: NCT04322604    
Other Study ID Numbers: AK002-016
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Allakos, Inc.:
Eosinophil
Eosinophilic
Eosinophilic gastrointestinal disorders
EGID
EG
EGE
Eosinophilic Gastritis
Eosinophilic Gastroenteritis
Eosinophilic Duodenitis
Additional relevant MeSH terms:
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Gastroenteritis
Gastritis
Eosinophilic Esophagitis
Enteritis
Duodenitis
Eosinophilia
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Esophagitis
Esophageal Diseases
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Intestinal Diseases
Duodenal Diseases