ENIGMA-SC: A Study to Assess Subcutaneous AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis

Sponsor

Allakos, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05152563

Collaborator

(none)

280

Enrollment

Locations

Arms

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, and pharmacodynamic effect of subcutaneous lirentelimab (AK002), given monthly for 6 doses, in subjects with moderate to severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis who have an inadequate response with, lost response to, or were intolerant to standard therapies.

Condition or Disease	Intervention/Treatment	Phase
Eosinophilic Gastritis Eosinophilic Duodenitis	Drug: AK002 Other: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of Subcutaneous AK002 in Subjects With Moderate to Severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SC 150 mg of lirentelimab (AK002) Subjects in this arm will receive 6 monthly doses of 150 mg of lirentelimab (AK002) administered subcutaneously.	Drug: AK002 Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8 Other Names: Lirentelimab
Experimental: SC 300 mg of lirentelimab (AK002) Subjects in this arm will receive 6 monthly doses of 300 mg of lirentelimab (AK002) administered subcutaneously.	Drug: AK002 Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8 Other Names: Lirentelimab
Experimental: SC 450 mg of lirentelimab (AK002) Subjects in this arm will receive 6 monthly doses of 450 mg of lirentelimab (AK002) administered subcutaneously.	Drug: AK002 Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8 Other Names: Lirentelimab
Other: Placebo Placebo	Other: Placebo Placebo

Outcome Measures

Primary Outcome Measures

Proportion of Responders as determined by gastric or duodenal tissue eosinophil counts. [At Week 24]
A responder is a subject achieving the following peak eosinophil counts: eosinophil count ≤4 cells per hpf in 5 gastric hpf and/or eosinophil count ≤15 cells per hpf in 3 duodenal hpf
Mean absolute change in 6 symptom total symptom score (TSS: abdominal pain, nausea, abdominal cramping, loss of appetite, fullness before finishing a meal, and bloating ) as measured by the PRO questionnaire (score from 0 none - 10 worst) [Baseline to Weeks 23 - 24]

Secondary Outcome Measures

Percent change in tissue eosinophils [Baseline to Week 24]
Number of treatment responders as defined by >30% improvement in symptoms and mean eosinophil count ≤4 cells/hpf in 5 gastric hpf and/or mean eosinophil count ≤15 cells/hpf in 3 duodenal hpf. [Baseline to Weeks 23-24 and at Week 24, respectively.]
Proportion of subjects achieving mean eosinophil count ≤1 cell/hpf in 5 highest gastric hpf and mean eosinophil count ≤1 cell/hpf in 3 highest duodenal hpf [At Week 24]
Proportion of subjects who show ≥50% reduction in TSS [Baseline to Weeks 23-24]
Proportion of subjects who show ≥70% reduction in TSS [Baseline to Weeks 23-24]
Change in weekly TSS over time [Baseline to Weeks 23-24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provide written informed consent.
Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry.
Baseline endoscopic biopsy with ≥30 eosinophils/hpf in at least 5 hpf in the stomach and/or ≥30 eosinophils/hpf in at least 3 hpf in the duodenum as determined by central histology assessment of biopsies collected during the screening EGD without any other significant cause for the eosinophilia.
Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PRO questionnaire (score from 0-10) and a weekly average TSS of ≥10 for at least 2 weeks of screening.
Subjects with inadequate or loss of response to, or who were intolerant to standard therapies for EG and/or EoD, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
If subject is on preexisting dietary restrictions, willingness to maintain dietary restrictions throughout the study.
Willing and able to comply with all study procedures and visit schedule including follow-up visits.
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 (e.g., missed or late menstrual period) at any time during study participation.

Exclusion Criteria:

Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
Active Heliobacter pylori (H. pylori) infection as confirmed by stool antigen test for

pylori or identified in tissue biopsies obtained at screening EGD.

History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
History of bleeding disorders and/or esophageal varices considered to be clinically significant by the Investigator.
Other significant gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
Confirmed diagnosis of hypereosinophilic syndrome (HES).
Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the subject at increased risk.
History of malignancy, except carcinoma in situ, early-stage prostate cancer, or non-melanoma skin cancers. However, subjects with cancers that have been in remission for more than 5 years and are considered cured can be enrolled.
Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
Positive helminthic infection on Ova and Parasite (O&P) test.
Seropositive for Strongyloides stercoralis at screening.
Seropositive for HIV or hepatitis at screening except for vaccinated subjects or subjects with past but resolved hepatitis at screening.
Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study or expected during the treatment period. Vaccines authorized by FDA or other regulatory authority for the prevention of COVID-19 may be administered before, during, or after this protocol as per the label. The vaccine should not be administered within 7 days prior to and within 7 days after the administration of AK002 so that the side effects caused by either of the 2 medications can be more easily determined.
Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products).
Known history of alcohol, drug, or other substance abuse or dependence that is considered by the Investigator to be ongoing and clinically significant.
Any other reason that in the opinion of the Investigator or the Medical Monitor makes the subject unsuitable for enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allakos Investigational Site	Birmingham	Alabama	United States	35205
2	Allakos Investigational Site	Gilbert	Arizona	United States	85234
3	Allakos Investigational Site	Phoenix	Arizona	United States	85021
4	Allakos Investigational Site	Scottsdale	Arizona	United States	85250
5	Allakos Investigational Site	Chula Vista	California	United States	91910
6	Allakos Investigational Site	Long Beach	California	United States	90808
7	Allakos Investigational Site	Ventura	California	United States	93003
8	Allakos Investigational Site	Walnut Creek	California	United States	94598
9	Allakos Investigational Site	Bristol	Connecticut	United States	06010
10	Allakos Investigational Site	Brandon	Florida	United States	33511
11	Allakos Investigational Site	Edgewater	Florida	United States	32132
12	Allakos Investigational Site	Jacksonville	Florida	United States	32256
13	Allakos Investigational Site	Kissimmee	Florida	United States	34741
14	Allakos Investigational Site	Miami	Florida	United States	33125
15	Allakos Investigational Site	New Port Richey	Florida	United States	34653
16	Allakos Investigational Site	Ponte Vedra	Florida	United States	32081
17	Allakos Investigational Site	Sunrise	Florida	United States	33351
18	Allakos Investigational Site	Tampa	Florida	United States	33603
19	Allakos Investigational Site	Tampa	Florida	United States	33612
20	Allakos Investigational Site	Atlanta	Georgia	United States	30342
21	Allakos Investigational Site	Sandy Springs	Georgia	United States	30328
22	Allakos Investigational Site	Chicago	Illinois	United States	60611
23	Allakos Investigational Site	Iowa City	Iowa	United States	52242
24	Allakos Investigational Site	Kansas City	Kansas	United States	66160
25	Allakos Investigational Site	Crowley	Louisiana	United States	70526
26	Allakos Investigational Site	Shreveport	Louisiana	United States	71105
27	Allakos Investigational Site	Glen Burnie	Maryland	United States	21061
28	Allakos Investigational Site	Boston	Massachusetts	United States	02111
29	Allakos Investigational Site	Boston	Massachusetts	United States	02215
30	Allakos Investigational Site	Ann Arbor	Michigan	United States	48104
31	Allakos Investigational Site	Wyoming	Michigan	United States	49519
32	Allakos Investigational Site	Rochester	Minnesota	United States	55905
33	Allakos Investigational Site	Bay Saint Louis	Mississippi	United States	63106
34	Allakos Investigational Site	Flowood	Mississippi	United States	39232
35	Allakos Investigational Site	Kalispell	Montana	United States	59901
36	Allakos Investigational Site	Reno	Nevada	United States	89511
37	Allakos Investigational Site	Lebanon	New Hampshire	United States	03756
38	Allakos Investigational Site	Florham Park	New Jersey	United States	07932
39	Allakos Investigational Site	Freehold	New Jersey	United States	07728
40	Allakos Investigational Site	Great Neck	New York	United States	11023
41	Allakos Investigational Site	Chapel Hill	North Carolina	United States	27599
42	Allakos Investigational Site	Charlotte	North Carolina	United States	28204
43	Allakos Investigational Site	Concord	North Carolina	United States	28027
44	Allakos Investigational Site	Durham	North Carolina	United States	27710
45	Allakos Investigational Site	Raleigh	North Carolina	United States	27607
46	Allakos Investigational Site	Winston-Salem	North Carolina	United States	27157
47	Allakos Investigational Site	Cincinnati	Ohio	United States	45229
48	Allakos Investigational Site	Columbus	Ohio	United States	43210
49	Allakos Investigational Site	Dayton	Ohio	United States	45415
50	Allakos Investigational Site	Mentor	Ohio	United States	44060
51	Allakos Investigational Site	Springboro	Ohio	United States	45066
52	Allakos Investigational Site	Westlake	Ohio	United States	44145
53	Allakos Investigational Site	Oklahoma City	Oklahoma	United States	73102
54	Allakos Investigational Site	Philadelphia	Pennsylvania	United States	19104
55	Allakos Investigational Site	Greenwood	South Carolina	United States	29646
56	Allakos Investigational Site	Chattanooga	Tennessee	United States	37421
57	Allakos Investigational Site	Germantown	Tennessee	United States	38138
58	Allakos Investigational Site	Hixson	Tennessee	United States	37343
59	Allakos Investigational Site	Nashville	Tennessee	United States	37212
60	Allakos Investigational Site	Austin	Texas	United States	78757
61	Allakos Investigational Site	El Paso	Texas	United States	79905
62	Allakos Investigational Site	Fort Worth	Texas	United States	76104
63	Allakos Investigational Site	Lubbock	Texas	United States	79410
64	Allakos Investigational Site	San Antonio	Texas	United States	78229
65	Allakos Investigational Site	Southlake	Texas	United States	76092
66	Allakos Investigational Site	Webster	Texas	United States	77598
67	Allakos Investigational Site	Wichita Falls	Texas	United States	76301
68	Allakos Investigational Site	Ogden	Utah	United States	84405
69	Allakos Investigational Site	Riverton	Utah	United States	84065
70	Allakos Investigational Site	Salt Lake City	Utah	United States	84112
71	Allakos Investigational Site	Sandy	Utah	United States	84092
72	Allakos Investigational Site	Fairfax	Virginia	United States	22031
73	Allakos Investigational Site	Seattle	Washington	United States	98115
74	Allakos Investigational Site	Seattle	Washington	United States	98122