Eosinophilic Duodenitis, Eosinophilic Gastritis, Eosinophilic Gastroenteritis
Conditions
Keywords
Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophil, EG, EGE, EGID, Eosinophilic gastrointestinal disorders, Eosinophilic Duodenitis, EoD
Brief summary
This is a Phase 2, open-label, extension study to assess the safety and tolerability of AK002, given monthly for up to 26 doses.
Interventions
DRUGAK002
AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.
Sponsors
Allakos Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent. 2. Completed Study AK002-003, defined as having received 4 infusions of study drug and followed through Day 113 (±3 days) in Study AK002-003 or discontinued from treatment due to high eosinophil counts prior to infusions 2, 3, or 4 and willing to begin extended dosing on or about Day 113 (for AK002-003 completers) or within 6 months of last dosing for patients discontinued from treatment. 3. If patient is on pre-existing dietary restrictions, willingness to note any changes that occur from the Baseline diet, throughout the study. 4. Able and willing to comply with all study procedures. 5. Female patients must be either post-menopausal for at least 1 year 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 until the end of the study, or for 120 days following the last dose of study drug, whichever is longer. 6. Male patients with female partners of childbearing potential must agree to use a highly effective method of contraception 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.
Exclusion criteria
1. Poor tolerance to previous administration of AK002 in the opinion of the Investigator. 2. Known hypersensitivity to any constituent of the study drug. 3. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk. 4. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration. All types and formulations of vaccines (including live attenuated vaccines) authorized by FDA or other regulatory authority for the prevention of COVID-19 may be administered before, during, or after this study. The vaccine should not be administered within 7 days prior to and within 7 days after the administration of AK002 so that any side effects caused by either of the 2 medications can be more easily determined. 5. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study. 6. Any other reason that, in the opinion of the Investigator or Medical Monitor, makes the patient unsuitable for enrollment. 7. Diagnosis of Hypereosinophilic Syndrome (HES), based on standard criteria (blood eosinophils \>1500/µL with involvement of either the heart, nervous system, and/or bone marrow).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Through study completion, up to 28 months | Adverse events assessed using the CTCAE version 4.03 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in PRO Total Symptom Score (TSS) From AK002-003 Baseline | AK002-003 Baseline to End of Treatment (2 weeks post last dose, up to 26 months) | 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. The End of treatment TSS score is defined as the average of the 14 daily scores on or after the day of the last dose of the extension study. |
| Changes in the Number of Eosinophils in Gastric and/or Duodenal Mucosa From AK002-003 Baseline | AK002-003 Baseline to Day 547 | Percentage of Change in the Number of Eosinophils in Gastric and/or Duodenal Mucosa in each group from AK002-003 Baseline |
Countries
United States
Participant flow
Recruitment details
The participants who were enrolled in and completed the study NCT03496571 had the option to participate in this open-label extension study.
Participants by arm
| Arm | Count |
|---|---|
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 Subjects in this arm received the placebo in the main study (AK002-003) and were treated with 26 monthly doses of AK002: a first dose of 1 mg/kg, followed by monthly doses of 3 mg/kg.
AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8. | 21 |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 Subjects in this arm received the active drug in the main study (AK002-003) and were treated with 26 monthly doses of AK002: a first dose of 1 mg/kg, followed by monthly doses of 3 mg/kg.
AK002: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8. | 37 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Sponsor Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 14 |
Baseline characteristics
| Characteristic | Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | Total | Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 |
|---|---|---|---|
| Age, Continuous | 35 years | 40 years | 43 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 53 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 54 Participants | 33 Participants |
| Region of Enrollment United States | 21 Participants | 58 Participants | 37 Participants |
| Sex: Female, Male Female | 9 Participants | 35 Participants | 26 Participants |
| Sex: Female, Male Male | 12 Participants | 23 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 37 |
| other Total, other adverse events | 20 / 21 | 32 / 37 |
| serious Total, serious adverse events | 2 / 21 | 9 / 37 |
Outcome results
Primary
The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03
Adverse events assessed using the CTCAE version 4.03
Time frame: Through study completion, up to 28 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 treatment-related adverse events | 15 Participants |
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 serious adverse events | 2 Participants |
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with an adverse event leading to study discontinuation | 0 Participants |
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 treatment-related serious adverse events | 0 Participants |
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 adverse events | 21 Participants |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 treatment-related serious adverse events | 0 Participants |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 adverse events | 35 Participants |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 treatment-related adverse events | 22 Participants |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with an adverse event leading to study discontinuation | 3 Participants |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | The Safety and Tolerability of AK002 by Evaluating Adverse Events Assessed Using the CTCAE Version 4.03 | Subjects with ≥1 serious adverse events | 9 Participants |
Secondary
Changes in the Number of Eosinophils in Gastric and/or Duodenal Mucosa From AK002-003 Baseline
Percentage of Change in the Number of Eosinophils in Gastric and/or Duodenal Mucosa in each group from AK002-003 Baseline
Time frame: AK002-003 Baseline to Day 547
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | Changes in the Number of Eosinophils in Gastric and/or Duodenal Mucosa From AK002-003 Baseline | -93.5 Percentage of change | Standard Deviation 18.9 |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | Changes in the Number of Eosinophils in Gastric and/or Duodenal Mucosa From AK002-003 Baseline | -99.7 Percentage of change | Standard Deviation 0.7 |
Secondary
Percent Change in PRO Total Symptom Score (TSS) From AK002-003 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. The End of treatment TSS score is defined as the average of the 14 daily scores on or after the day of the last dose of the extension study.
Time frame: AK002-003 Baseline to End of Treatment (2 weeks post last dose, up to 26 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study Placebo to Extension Study 1 to 3.0 mg/kg of AK002 | Percent Change in PRO Total Symptom Score (TSS) From AK002-003 Baseline | -66.3 Percentage of change | Standard Deviation 27.7 |
| Main Study Active to Extension Study 1 to 3.0 mg/kg of AK002 | Percent Change in PRO Total Symptom Score (TSS) From AK002-003 Baseline | -60.6 Percentage of change | Standard Deviation 32.4 |