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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04322708




Registration number
NCT04322708
Ethics application status
Date submitted
24/03/2020
Date registered
26/03/2020

Titles & IDs
Public title
A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Esophagitis
Scientific title
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
Secondary ID [1] 0 0
AK002-014
Universal Trial Number (UTN)
Trial acronym
KRYPTOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Eosinophilic Esophagitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Placebo
Treatment: Drugs - lirentelimab (AK002)

Placebo comparator: Placebo - Subjects in this arm will receive 6 monthly doses of placebo.

Experimental: 1 mg/kg of lirentelimab (AK002) - Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) (1mg/kg).

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.


Other interventions: Placebo
Placebo

Treatment: Drugs: lirentelimab (AK002)
Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of =6 Eosinophils/Hpf at Week 24
Timepoint [1] 0 0
At Week 24
Primary outcome [2] 0 0
Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.
Timepoint [2] 0 0
Baseline to Weeks 23-24
Secondary outcome [1] 0 0
Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [2] 0 0
Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of =1 Eosinophil/Hpf at Week 24
Timepoint [2] 0 0
At Week 24
Secondary outcome [3] 0 0
Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24
Timepoint [3] 0 0
At Week 24
Secondary outcome [4] 0 0
Number of Treatment Responders
Timepoint [4] 0 0
At Weeks 23-24 and Week 24, Respectively
Secondary outcome [5] 0 0
Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24
Timepoint [5] 0 0
Weeks 23-24
Secondary outcome [6] 0 0
Percent Change in DSQ Score From Baseline to Weeks 23-24
Timepoint [6] 0 0
Baseline to Weeks 23-24
Secondary outcome [7] 0 0
Change in Biweekly Mean DSQ Over Time Using MMRM
Timepoint [7] 0 0
Baseline to Weeks 23-24
Secondary outcome [8] 0 0
Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24
Timepoint [8] 0 0
Baseline to Week 24

Eligibility
Key inclusion criteria
Key

1. Male or female aged =12 and =80 years at the time of signing ICF.
2. 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.
3. 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.
4. 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.
5. 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.
6. If patient 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 >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
Minimum age
12 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Concomitant EG, EoD, or eosinophilic colitis (EC).
2. 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.
3. 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.
4. History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
5. 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.
6. History of bleeding disorders or esophageal varices.
7. 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.
8. 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.
9. 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.
10. Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.
11. Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
12. Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.
13. Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.
14. 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.
15. 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.
16. 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.
17. Treatment with chemotherapy or radiotherapy in the preceding 6 months.
18. Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
19. Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk.
20. Known history of alcohol, drug, or other substance abuse or dependence.
21. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
22. Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/01/2022
Sample size
Target
Accrual to date
Final
277
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Allakos Investigational Site - Adelaide
Recruitment hospital [2] 0 0
Allakos Investigational Site - Elizabeth Vale
Recruitment hospital [3] 0 0
Allakos Investigational Site - Box Hill
Recruitment hospital [4] 0 0
Allakos Investigational Site - Prahran
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Massachusetts
Country [15] 0 0
United States of America
State/province [15] 0 0
Michigan
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Montana
Country [18] 0 0
United States of America
State/province [18] 0 0
Nevada
Country [19] 0 0
United States of America
State/province [19] 0 0
New York
Country [20] 0 0
United States of America
State/province [20] 0 0
North Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oklahoma
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
South Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
Tennessee
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Utah
Country [28] 0 0
United States of America
State/province [28] 0 0
Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
Washington
Country [30] 0 0
Netherlands
State/province [30] 0 0
North Holland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Allakos Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Craig Paterson, MD
Address 0 0
Allakos Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04322708