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This is a Phase 2, double-blind, randomized, placebo-controlled study to assess the effects of AK002, given monthly for 4 doses. It is hypothesized that AK002 is more effective than placebo control (alternative hypothesis) in reducing the number of eosinophils per high power field (HPF) in gastric and/or duodenal biopsies before and after receiving AK002 or placebo versus no difference between AK002 and placebo control (null hypothesis).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Subjects in this arm will receive 4 monthly doses of placebo. |
|
| 1 mg/kg of AK002 | Experimental | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg |
|
| 3 mg/kg of AK002 | Experimental | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AK002 | Drug | AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline | Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro- duodenoscopy (EGD) | Baseline to Day 99 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Treatment Responders | Treatment Responders defined by >30% improvement in TSS and a reduction of >75% in eosinophils in gastric and/or duodenal mucosa. The eosinophil count is obtained on Day 99 and the TSS score is the average of the daily scores from Days 85-99. | On Days 85-99 and Day 99, respectively |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Henrik Rasmussen, MD, PhD | Allakos Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenician Centers for Research and Innovation | Phoenix | Arizona | 85021 | United States | ||
| Mayo Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38423296 | Derived | Fu J, Sia T, Solecki R, Mallik S, Khuda R, Headen M, Bacchus L, Zheng M, Telukunta T, Shami S, Liu S, Sureshbabu S, Love K, Roby A, McDonald P, Jiang Y, Narayanan DH, Cunningham E, Matmatte AS, Tan PE, Leung J. Clinical and histologic remission achieved with upadacitinib in a patient with refractory eosinophilic gastritis and duodenitis. J Allergy Clin Immunol Pract. 2024 Jun;12(6):1649-1651. doi: 10.1016/j.jaip.2024.02.031. Epub 2024 Feb 27. No abstract available. | |
| 34089846 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 mg/kg of AK002 | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg. AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 25, 2019 | Dec 14, 2023 |
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| Placebo | Other | Placebo |
|
| Percent Change in PRO Total Symptom Score (TSS) From Baseline |
The PRO Total Symptom Score (TSS) is a patient-reported outcome (PRO) questionnaire comprises the following 8 symptoms: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating, and diarrhea. Individual symptom scores ranged from 0 to 10. The daily total symptom score ranged from 0 to 80, with higher scores indicating greater severity. TSS score at the End of Study is the average of the daily scores from Days 85-99. |
| Baseline to Days 85-99 |
| Scottsdale |
| Arizona |
| 85259 |
| United States |
| Ventura Clinical Trials | Ventura | California | 93003 | United States |
| UC Denver | Aurora | Colorado | 80045 | United States |
| Riverside Clinical Research | Edgewater | Florida | 32132 | United States |
| Advanced Research Institute | New Port Richey | Florida | 34653 | United States |
| Northwestern | Chicago | Illinois | 60611 | United States |
| Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| National Institutes of Health | Bethesda | Maryland | 20892 | United States |
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| University of North Carolina - Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Cincinnati Children's Hospital | Cincinnati | Ohio | 45229 | United States |
| University of Pennsylvania, Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania | 19104 | United States |
| Care Access Research | Pottsville | Pennsylvania | 17901 | United States |
| ClinSearch | Chattanooga | Tennessee | 37421 | United States |
| Vanderbilt University | Nashville | Tennessee | 37212 | United States |
| Avant Research Associates | Austin | Texas | 78704 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| Derived |
| Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, Chehade M, Peterson KA, Falk GW, Murray JA, Gehman LT, Chang AT, Singh B, Rasmussen HS, Genta RM. Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab. Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2. |
| 33085861 | Derived | Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, Genta RM, Leung J, Khoury P, Klion AD, Hazan S, Vaezi M, Bledsoe AC, Durrani SR, Wang C, Shaw C, Chang AT, Singh B, Kamboj AP, Rasmussen HS, Rothenberg ME, Hirano I. Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis. N Engl J Med. 2020 Oct 22;383(17):1624-1634. doi: 10.1056/NEJMoa2012047. |
| FG001 | 3 mg/kg of AK002 | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg. AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). |
| FG002 | Placebo | Subjects in this arm will receive 4 monthly doses of placebo. Placebo: Placebo. |
| COMPLETED |
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| NOT COMPLETED |
|
Intention-to-treat
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 mg/kg of AK002 | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg. AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). |
| BG001 | 3 mg/kg of AK002 | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg. AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). |
| BG002 | Placebo | Subjects in this arm will receive 4 monthly doses of placebo. Placebo: Placebo |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Baseline Gastrointestinal Eosinophil Count | Number of eosinophils per high power field (HPF) in gastric or duodenal mucosa | Mean | Standard Deviation | Eosinophils/HPF |
| ||||||||||||||
| PRO Total Symptom Score (TSS) | The PRO Total Symptom Score (TSS) is a patient-reported outcome (PRO) questionnaire comprises the following 8 symptoms: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating, and diarrhea. Individual symptom scores ranged from 0 to 10. The daily total symptom score ranged from 0 to 80, with higher scores indicating greater severity. TSS score at the End of Study is the average of the daily scores from Days 85-99. | Mean | Standard Deviation | Score on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in the Number of Eosinophils Per High Power Field in Gastric or Duodenal Mucosa From Baseline | Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro- duodenoscopy (EGD) | Intention-to-treat | Posted | Mean | 95% Confidence Interval | Percentage of Change | Baseline to Day 99 |
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| Secondary | Number of Treatment Responders | Treatment Responders defined by >30% improvement in TSS and a reduction of >75% in eosinophils in gastric and/or duodenal mucosa. The eosinophil count is obtained on Day 99 and the TSS score is the average of the daily scores from Days 85-99. | Intention-to-treat | Posted | Count of Participants | Participants | On Days 85-99 and Day 99, respectively |
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| Secondary | Percent Change in PRO Total Symptom Score (TSS) From Baseline | The PRO Total Symptom Score (TSS) is a patient-reported outcome (PRO) questionnaire comprises the following 8 symptoms: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating, and diarrhea. Individual symptom scores ranged from 0 to 10. The daily total symptom score ranged from 0 to 80, with higher scores indicating greater severity. TSS score at the End of Study is the average of the daily scores from Days 85-99. | Intention-to-treat | Posted | Mean | 95% Confidence Interval | Percentage of Change | Baseline to Days 85-99 |
|
Baseline up to Day 113
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 mg/kg of AK002 | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg. AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). | 0 | 22 | 2 | 22 | 20 | 22 |
| EG001 | 3 mg/kg of AK002 | Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg. AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). | 0 | 21 | 2 | 21 | 15 | 21 |
| EG002 | Placebo | Subjects in this arm will receive 4 monthly doses of placebo. Placebo: Placebo | 0 | 22 | 3 | 22 | 17 | 22 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Mental Status Change | Psychiatric disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Iron def anemia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Chest pain | General disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | CTCAE 5.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion related reaction | Injury, poisoning and procedural complications | CTCAE 5.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | CTCAE 5.0 | Systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | CTCAE 5.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE 5.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
Clinical Trial Agreement contains a limit on publication of results following completion of the trial. PIs are not allowed to publish results until a joint publication for the multicenter study or a set period of time. After that time, PIs may only publish results from their portion of the study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Allakos | 650-597-5002 | medinfo@allakos.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 29, 2019 | Dec 13, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| C535952 | Eosinophilic enteropathy |
| D057765 | Eosinophilic Esophagitis |
| ID | Term |
|---|---|
| D004941 | Esophagitis |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D005759 | Gastroenteritis |
| D004802 | Eosinophilia |
| D007960 | Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000654568 | AK002 |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| LSM Difference from Placebo |
| -102 |
| 2-Sided |
| 95 |
| -128 |
| -76 |
| Superiority |
| ANCOVA | <0.001 | LSM Difference from Placebo | -98 | 2-Sided | 95 | -121 | -76 | Superiority |
Combined group of 1 mg/kg of AK002 and 3 mg/kg of AK002.
| OG003 | Placebo | Subjects in this arm will receive 4 monthly doses of placebo. Placebo: Placebo |
|
|
|
| OG002 | Combined AK002 | Combined group of 1 mg/kg of AK002 and 3 mg/kg of AK002. |
| OG003 | Placebo | Subjects in this arm will receive 4 monthly doses of placebo. Placebo: Placebo |
|
|
|