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NCT03496571: ENIGMA

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

Completed Phase 2 Results posted Last updated 19 January 2024
What this trial tests

Phase 2 trial testing AK002 in Eosinophilic Gastritis in 65 participants. Completed in 24 June 2019.

Timeline
18 July 2018
Primary endpoint
24 June 2019
24 June 2019

Quick facts

Lead sponsorAllakos Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment65
Start date18 July 2018
Primary completion24 June 2019
Estimated completion24 June 2019
Sites21 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Allakos Inc. — full company profile →

Who can join

Adults 18 to 80, any sex, with Eosinophilic Gastritis or Eosinophilic Gastroenteritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline Primary · Baseline to Day 99

Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro- duodenoscopy (EGD)

GroupValue95% CI
1 mg/kg of AK002-79-95 – -59
3 mg/kg of AK002-92-100 – -81
Combined AK002-86-94 – -71
Placebo9-15 – 31
Number of Treatment Responders Secondary · On Days 85-99 and Day 99, respectively

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.

GroupValue95% CI
1 mg/kg of AK00213
3 mg/kg of AK00214
Combined AK00227
Placebo1
Percent Change in PRO Total Symptom Score (TSS) From Baseline Secondary · Baseline to Days 85-99

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.

GroupValue95% CI
1 mg/kg of AK002-42-56 – -28
3 mg/kg of AK002-55-70 – -40
Combined AK002-48-58 – -39
Placebo-22-37 – -7

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Day 113. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1 mg/kg of AK002
Serious: 2/22 (9%)
Deaths: 0/22
3 mg/kg of AK002
Serious: 2/21 (10%)
Deaths: 0/21
Placebo
Serious: 3/22 (14%)
Deaths: 0/22

Serious adverse events (8 terms)

ReactionSystem1 mg/kg of AK0023 mg/kg of AK002Placebo
HypoxiaRespiratory, thoracic and mediastinal disorders
Mental Status ChangePsychiatric disorders
AnemiaBlood and lymphatic system disorders
Iron def anemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Chest painGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
DehydrationMetabolism and nutrition disorders
Other adverse events (20 terms — click to expand)

ReactionSystem1 mg/kg of AK0023 mg/kg of AK002Placebo
Infusion related reactionInjury, poisoning and procedural complications
HeadacheNervous system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
DiarrheaGastrointestinal disorders
NasopharyngitisInfections and infestations
Abdominal painGastrointestinal disorders
Gastroenteritis viralInfections and infestations
PyrexiaGeneral disorders
SinusitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
InfluenzaInfections and infestations
White blood cell count increasedInvestigations
Gastroesophageal reflux diseaseGastrointestinal disorders
Blood glucose increasedInvestigations
Muscle spasmsMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
AsthmaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Hypoxia, Mental Status Change, Anemia, Iron def anemia, Abdominal pain, Chest pain, Infusion related reaction, Dehydration.

Data from ClinicalTrials.gov NCT03496571 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The clinical impact of glycobiology: targeting selectins, Siglecs and mammalian glycans.
    Smith BAH, Bertozzi CR. · · 2021 · cited 380× · PMID 33462432 · DOI 10.1038/s41573-020-00093-1
  2. Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis.
    Dellon ES, Peterson KA, Murray JA, Falk GW, et al · · 2020 · cited 213× · PMID 33085861 · DOI 10.1056/nejmoa2012047
  3. AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice.
    Youngblood BA, Brock EC, Leung J, Falahati R, et al · · 2019 · cited 89× · PMID 31401630 · DOI 10.1159/000501637
  4. Eosinophil and mast cell Siglecs: From biology to drug target.
    O'Sullivan JA, Chang AT, Youngblood BA, Bochner BS. · · 2020 · cited 53× · PMID 31965606 · DOI 10.1002/jlb.2mr0120-352rr
  5. Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab.
    Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, et al · · 2022 · cited 45× · PMID 34089846 · DOI 10.1016/j.cgh.2021.05.053
  6. Hypereosinophilic syndrome: approach to treatment in the era of precision medicine.
    Klion A. · · 2018 · cited 41× · PMID 30504328 · DOI 10.1182/asheducation-2018.1.326
  7. Single-Organ and Multisystem Hypereosinophilic Syndrome Patients with Gastrointestinal Manifestations Share Common Characteristics.
    Kuang FL, Curtin BF, Alao H, Piligian B, et al · · 2020 · cited 29× · PMID 32344186 · DOI 10.1016/j.jaip.2020.04.025
  8. Novel Approaches in the Inhibition of IgE-Induced Mast Cell Reactivity in Food Allergy.
    Tontini C, Bulfone-Paus S. · · 2021 · cited 24× · PMID 34456900 · DOI 10.3389/fimmu.2021.613461

Verify or expand the search:

Other trials of AK002

Trials testing the same drug.

Other recruiting trials for Eosinophilic Gastritis

Currently open trials in the same condition.

Other Allakos Inc. trials

Trials by the same sponsor.

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