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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04322708
Ethics application status
Date submitted
24/03/2020
Date registered
26/03/2020
Date last updated
25/11/2020

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
The proportion of patients who achieve esophageal intraepithelial eosinophil count of =6 eosinophils/hpf
Timepoint [1] 0 0
At Week 24
Primary outcome [2] 0 0
Mean absolute change in Dysphagia Symptom Questionnaire (DSQ) score
Timepoint [2] 0 0
Baseline to Weeks 23-24
Secondary outcome [1] 0 0
Percent change in esophageal intraepithelial eosinophil count
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [2] 0 0
Proportion of patients achieving esophageal intraepithelial eosinophil count of =1 eosinophil/hpf
Timepoint [2] 0 0
At Week 24
Secondary outcome [3] 0 0
Proportion of patients achieving esophageal intraepithelial eosinophil count of =15 eosinophil/hpf
Timepoint [3] 0 0
At Week 24
Secondary outcome [4] 0 0
Proportion of treatment responders when a responder is a patient achieving >30% reduction in symptoms (DSQ) and achieving a peak intraepithelial eosinophilic count of =6 eosinophils/hpf
Timepoint [4] 0 0
At Weeks 23-24
Secondary outcome [5] 0 0
Proportion of patients with >50% reduction in DSQ score
Timepoint [5] 0 0
Baseline to Weeks 23-24
Secondary outcome [6] 0 0
Percent change in DSQ score
Timepoint [6] 0 0
Baseline to Weeks 23-24
Secondary outcome [7] 0 0
Change in biweekly mean DSQ over time.
Timepoint [7] 0 0
Baseline to Weeks 23-24
Secondary outcome [8] 0 0
Absolute change in EoE Reference Score for Endoscopic Abnormalities (EREFS)
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
Gender
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/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 - Box Hill
Recruitment postcode(s) [1] 0 0
5128 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
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
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Montana
Country [17] 0 0
United States of America
State/province [17] 0 0
Nevada
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oklahoma
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
South Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Tennessee
Country [25] 0 0
United States of America
State/province [25] 0 0
Texas
Country [26] 0 0
United States of America
State/province [26] 0 0
Utah
Country [27] 0 0
Netherlands
State/province [27] 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
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.
Trial website
https://clinicaltrials.gov/show/NCT04322708
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Henrik Rasmussen, MD, PhD
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
Henrik Rasmussen, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
443-699-5230
Fax 0 0
Email 0 0
hrasmussen@allakos.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04322708