- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04322708
A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Esophagitis (KRYPTOS)
December 13, 2023 updated by: Allakos Inc.
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lirentelimab (AK002) in Adult and Adolescent Patients With Active Eosinophilic Esophagitis
This is a Phase 2/3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult and adolescent patients with active eosinophilic esophagitis.
Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
277
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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South Australia
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Adelaide, South Australia, Australia, 5000
- Allakos Investigational Site
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Elizabeth Vale, South Australia, Australia, 5112
- Allakos Investigational Site
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Victoria
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Box Hill, Victoria, Australia, 3128
- Allakos Investigational Site
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Prahran, Victoria, Australia, 3181
- Allakos Investigational Site
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North Holland
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Amsterdam, North Holland, Netherlands, 1105 AZ
- Allakos Investigational Site
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Alabama
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Birmingham, Alabama, United States, 35209
- Allakos Investigational Site
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Huntsville, Alabama, United States, 38801
- Allakos Investigational Site
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Arizona
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Gilbert, Arizona, United States, 85234
- Allakos Investigational Site
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Phoenix, Arizona, United States, 85016
- Allakos Investigational Site
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Phoenix, Arizona, United States, 85021
- Allakos Investigational Site
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Scottsdale, Arizona, United States, 85251
- Allakos Investigational Site
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Arkansas
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Little Rock, Arkansas, United States, 72205
- Allakos Investigational Site
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California
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La Jolla, California, United States, 92037
- Allakos Investigational Site
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Los Angeles, California, United States, 90025
- Allakos Investigational Site
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Oakland, California, United States, 94612
- Allakos Investigational Site
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Santa Monica, California, United States, 90404
- Allakos Investigational Site
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Tustin, California, United States, 92780
- Allakos Investigational Site
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Ventura, California, United States, 93003
- Allakos Investigational Site
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Walnut Creek, California, United States, 94598
- Allakos Investigational Site
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Colorado
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Aurora, Colorado, United States, 80045
- Allakos Investigational Site
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Centennial, Colorado, United States, 80112
- Allakos Investigational Site
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Florida
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Brandon, Florida, United States, 33511
- Allakos Investigational Site
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Edgewater, Florida, United States, 32132
- Allakos Investigational Site
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Jacksonville, Florida, United States, 32256
- Allakos Investigational Site
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Miami, Florida, United States, 33176
- Allakos Investigational Site
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Orlando, Florida, United States, 32803
- Allakos Investigational Site
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Orlando, Florida, United States, 32806
- Allakos Investigational Site
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Tampa, Florida, United States, 33603
- Allakos Investigational Site
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Tampa, Florida, United States, 33615
- Allakos Investigational Site
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Georgia
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Atlanta, Georgia, United States, 30342
- Allakos Investigational Site
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Columbus, Georgia, United States, 31904
- Allakos Investigational Site
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Illinois
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Chicago, Illinois, United States, 60611
- Allakos Investigational Site
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Indiana
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Indianapolis, Indiana, United States, 46202
- Allakos Investigational Site
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Iowa
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Iowa City, Iowa, United States, 52242
- Allakos Investigational Site
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Kentucky
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Lexington, Kentucky, United States, 40503
- Allakos Investigational Site
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Louisiana
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Crowley, Louisiana, United States, 70526
- Allakos Investigational Site
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Maryland
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Chevy Chase, Maryland, United States, 20815
- Allakos Investigational Site
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Massachusetts
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Boston, Massachusetts, United States, 02111
- Allakos Investigational Site
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Boston, Massachusetts, United States, 02115
- Allakos Investigational Site
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Boston, Massachusetts, United States, 02215
- Allakos Investigational Site
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Michigan
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Ann Arbor, Michigan, United States, 48109
- Allakos Investigational Site
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Troy, Michigan, United States, 48098
- Allakos Investigational Site
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Missouri
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Kansas City, Missouri, United States, 64108
- Allakos Investigational Site
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Montana
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Kalispell, Montana, United States, 59901
- Allakos Investigational Site
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Nevada
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Las Vegas, Nevada, United States, 89106
- Allakos Investigational Site
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Reno, Nevada, United States, 89511
- Allakos Investigational Site
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New York
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Great Neck, New York, United States, 11021
- Allakos Investigational Site
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New York, New York, United States, 10029
- Allakos Investigational Site
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North Carolina
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Asheville, North Carolina, United States, 28801
- Allakos Investigational Site
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Chapel Hill, North Carolina, United States, 27599
- Allakos Investigational Site
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Charlotte, North Carolina, United States, 28210
- Allakos Investigational Site
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Charlotte, North Carolina, United States, 28277
- Allakos Investigational Site
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Durham, North Carolina, United States, 27710
- Allakos Investigational Site
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High Point, North Carolina, United States, 27262
- Allakos Investigational Site
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Rocky Mount, North Carolina, United States, 27804
- Allakos Investigational Site
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Ohio
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Akron, Ohio, United States, 44302
- Allakos Investigational Site
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Cincinnati, Ohio, United States, 45231
- Allakos Investigational Site
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Cincinnati, Ohio, United States, 45229
- Allakos Investigational Site
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Cleveland, Ohio, United States, 44106
- Allakos Investigational Site
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Dayton, Ohio, United States, 45415
- Allakos Investigational Site
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Mentor, Ohio, United States, 44060
- Allakos Investigational Site
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73112
- Allakos Investigational Site
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Pennsylvania
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Danville, Pennsylvania, United States, 17822
- Allakos Investigational Site
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Philadelphia, Pennsylvania, United States, 19104
- Allakos Investigational Site
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South Carolina
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Greenville, South Carolina, United States, 29615
- Allakos Investigational Site
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Tennessee
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Chattanooga, Tennessee, United States, 37421
- Allakos Investigational Site
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Hixson, Tennessee, United States, 37343
- Allakos Investigational Site
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Nashville, Tennessee, United States, 37212
- Allakos Investigational Site
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Texas
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Austin, Texas, United States, 78704
- Allakos Investigational Site
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Garland, Texas, United States, 75044
- Allakos Investigational Site
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San Antonio, Texas, United States, 78229
- Allakos Investigational Site
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Utah
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Ogden, Utah, United States, 84405
- Allakos Investigational Site
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Riverton, Utah, United States, 84065
- Allakos Investigational Site
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Salt Lake City, Utah, United States, 84132
- Allakos Investigational Site
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Sandy, Utah, United States, 84092
- Allakos Investigational Site
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Virginia
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Leesburg, Virginia, United States, 20176
- Allakos Investigational Site
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Washington
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Seattle, Washington, United States, 98105
- Allakos Investigational Site
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Seattle, Washington, United States, 98115
- Allakos Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 80 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Key Inclusion Criteria:
- Male or female aged ≥12 and ≤80 years at the time of signing ICF.
- Confirmed diagnosis of EoE and esophageal 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.
- 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.
- 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.
- If on an allowed treatment for EoE, stable dose for at least 4 weeks prior to Screening and willingness to continue that dose for the study duration.
- If patient 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 >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 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.
Key Exclusion Criteria:
- Concomitant EG, EoD, or eosinophilic colitis (EC).
- EG and/or EoD (≥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.
- Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute eosinophil count of >1500 eosinophils/μL.
- History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
- 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.
- History of bleeding disorders or esophageal varices.
- 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.
- Active Helicobacter 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.
- 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.
- Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.
- Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
- Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.
- Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.
- 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), anti-IgE (e.g., omalizumab), within 12 weeks prior to Screening.
- 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.
- 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.
- Treatment with chemotherapy or radiotherapy in the preceding 6 months.
- Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
- Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk.
- Known history of alcohol, drug, or other substance abuse or dependence.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Subjects in this arm will receive 6 monthly doses of placebo.
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Placebo
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Experimental: 1 mg/kg of lirentelimab (AK002)
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) (1mg/kg).
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Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
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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.
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Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24
Time Frame: At Week 24
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Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
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At Week 24
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Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.
Time Frame: Baseline to Weeks 23-24
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The DSQ is used to measure the frequency and intensity of dysphagia.
DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
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Baseline to Weeks 23-24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24
Time Frame: Baseline to Week 24
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Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
A greater esophageal intraepithelial eosinophil count from baseline indicates worsening disease.
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Baseline to Week 24
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Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24
Time Frame: At Week 24
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Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
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At Week 24
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Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24
Time Frame: At Week 24
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Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
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At Week 24
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Number of Treatment Responders
Time Frame: At Weeks 23-24 and Week 24, Respectively
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Treatment responders defined by >30% improvement in symptoms (DSQ) at Weeks 23-24 and peak intraepithelial eosinophilic count of ≤6 cells/hpf at Week 24
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At Weeks 23-24 and Week 24, Respectively
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Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24
Time Frame: Weeks 23-24
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The DSQ is used to measure the frequency and intensity of dysphagia.
DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
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Weeks 23-24
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Percent Change in DSQ Score From Baseline to Weeks 23-24
Time Frame: Baseline to Weeks 23-24
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The DSQ is used to measure the frequency and intensity of dysphagia.
DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
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Baseline to Weeks 23-24
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Change in Biweekly Mean DSQ Over Time Using MMRM
Time Frame: Baseline to Weeks 23-24
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The DSQ is used to measure the frequency and intensity of dysphagia.
DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
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Baseline to Weeks 23-24
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Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24
Time Frame: Baseline to Week 24
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EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease.
The overall total score ranges from 0 to 18 with higher number indicating worse disease.
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Baseline to Week 24
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Craig Paterson, MD, Allakos Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 6, 2020
Primary Completion (Actual)
June 4, 2021
Study Completion (Actual)
January 18, 2022
Study Registration Dates
First Submitted
March 24, 2020
First Submitted That Met QC Criteria
March 24, 2020
First Posted (Actual)
March 26, 2020
Study Record Updates
Last Update Posted (Estimated)
January 1, 2024
Last Update Submitted That Met QC Criteria
December 13, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AK002-014
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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