Principal Investigator: Kathryn Peterson
Keywords: Eosinophilic Esophagitis , EoE Department: Gastroenterology
IRB Number: 00130034
Specialty: Gastroenterology, Gastroenterology, Gastroenterology
Sub Specialties: Esophageal Diseases, Endoscopy
Recruitment Status: Not yet recruiting

Contact Information

Amy Holman
amy.holman@hsc.utah.edu
8015859155

Brief Summary

Primary Efficacy Objective

To evaluate the clinical benefit of AK002 in adult and adolescent patients with active EoE when compared to placebo, efficacy endpoints will be co-primary:

The proportion of patients who achieve a peak esophageal intraepithelial count of ≤6 eosinophils/hpf at Day 169 (Week 24).

Mean absolute change in Dysphagia Symptom Questionnaire (DSQ) score from Baseline to Weeks 23–24.

Secondary Objectives

To further evaluate the clinical benefit of AK002 in adult and adolescent patients with active EoE when compared to placebo as measured by:

  1. Percent change in peak esophageal intraepithelial eosinophil count at Day 169 (Week 24).

  2.  Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eosinophil/hpf at Day 169 (Week 24).

  3. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eosinophil/hpf at Day 169 (week 24). 

  4. Proportion of treatment responders where a responder is a patient achieving >30% reduction in symptoms (DSQ) at Weeks 23–24 and achieving a peak intraepithelial eosinophilic count of ≤6 eosinophils/hpf (Week 24).

  5. Proportion of patients with >50% reduction in DSQ score from Baseline to Weeks 23-24.

  6. Percent change in DSQ score from Baseline to Weeks 23–24.

  7. Change in biweekly mean DSQ over time.

  8. Absolute change in EoE Reference Score for Endoscopic Abnormalities (EREFS) from Baseline to Day 169 (Week 24).

Exploratory Objectives

The exploratory objectives are to further evaluate the effect of AK002 in adult and adolescent patients with active EoE by comparing AK002 to placebo for the following parameters:

  • Absolute change in EoE Histology Scoring System (EoEHSS) score from Baseline to Day 169 (Week 24).

  • Absolute change in health-related quality of life as measured by SF-36 Health and Well-Being Survey (SF-36) from Baseline to Day 169 (Week 24).

  • Absolute change in mast cell counts from Baseline to Day 169 (Week 24).

Safety Objectives

To evaluate the safety and tolerability of AK002 in adult and adolescent patients with active EoE by determining adverse event incidence and severity, study withdrawals due to adverse events, changes in vital signs and laboratory tests including immunogenicity, changes in concomitant medications beginning on or after the first infusion of study drug and other safety parameters.

Inclusion Criteria

  1. Male or female aged ≥18 and ≤80 years at the time of signing the ICF (adolescents are being included in this study, but will not be included locally). 

  2.  Confirmed diagnosis of EoE and intraepithelial eosinophilic infiltration of ≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD without any other cause for the esophageal eosinophilia. 

  3. Baseline DSQ (biweekly mean DSQ) score of ≥12 from the last 2 weeks of screening (the 14 days prior to the first dose) per the validated algorithm in Appendix 11.

  4. History (by patient report) of an average of ≥2 episodes of dysphagia with intake of solid foods per week during the 4 weeks prior to Screening.

  5. Subjects must have failed or not be adequately controlled on standard of care treatments for EoE symptoms, which could include PPI, systemic or topical corticosteroids, and/or diet, among others.

  6. If on an allowed treatment for EoE (per Section 8.2), stable dose for at least 4 weeks prior to Screening and willingness to continue that dose for the study duration.

  7.  If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.

  8. Able and willing to comply with all study procedures.

  9. Female subjects 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 either agree to use dual methods of contraception, have a partner who had a vasectomy, or agree to 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.

    Non-vasectomized male subjects with female partners of childbearing potential must agree to either abstain from sexual activity or 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. Concomitant moderately or severely symptomatic EG and/or EoD*, defined as              ≥30 eosinophils/hpf in 5 hpf in the stomach (EG) and/or ≥30 eosinophils/hpf in 3 hpf in the duodenum (EoD) without any other cause for eosinophilia as determined by central histology assessment of biopsies collected during the Screening EGD and an EG/EoD PRO Questionnaire weekly average single symptom score of ≥3 during the last 2 weeks of Screening for 1 of the following symptoms: abdominal pain, nausea, and/or diarrhea.   * This exclusion criterion is only applicable to sites actively enrolling patients in the AK002-016 study. If a site is not actively screening and enrolling patients in the AK002-016 study, then this exclusion criterion is not applicable.

  2. Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute eosinophil count >1500 eosinophils/μL.

  3. History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.

  4. Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mm upper endoscope or any critical esophageal stricture that requires dilation during screening.

  5. History of bleeding disorders or esophageal varices.

  6. 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). 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. Active Heliobacter pylori infection as determined by central histology staining of the biopsy collected during the Screening EGD unless treated and confirmed to be negative prior to randomization and symptoms remain consistent. 

  8. Positive Ova and Parasite (O&P) test at Screening, seropositive for Strongyloides stercoralis at Screening, and/or treatment for a clinically significant helminthic parasitic infection within 6 months of Screening.

  9. Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.

  10. Prior exposure to AK002 or hypersensitivity to any constituent of AK002.

  11. Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.

  12.  Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.

  13. Use of any biologics or medications that may interfere with the study, such as immunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor (e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab), anti-IL-13 (e.g., lebrikizumab), and anti-IgE (e.g., omalizumab), within 12 weeks prior to Screening.

  14. 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.

  15. Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected ≤5 half-lives (≤4 months) following study drug administration (with the exception of a COVID-19 vaccine authorized by the FDA or other applicable regulatory agency).

  16. Treatment with chemotherapy or radiotherapy in the preceding 6 months.

  17. Presence of abnormal laboratory values considered by the Investigator to be clinically significant.

  18. Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk.

  19. Known history of alcohol, drug, or other substance abuse or dependence.

  20. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.

  21. Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.