Eosinophilic Duodenitis, Eosinophilic Gastritis
Conditions
Brief summary
This is a Phase 3, open-label, extension study to assess the long term efficacy and safety of lirentelimab given monthly.
Interventions
DRUGlirentelimab
Lirentelimab (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
Key Inclusion Criteria: 1. Provide written informed consent. 2. Completed Study AK002-016, defined as having received 6 infusions of study drug and followed through Day 176 (±3) or completed Study AK002-012, defined as having received the cohort-appropriate amount of doses and followed for 5 months after last dose of study drug. 3. If patient is on pre-existing dietary restrictions, willingness to maintain those restrictions, 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. Key
Exclusion criteria
1. Known hypersensitivity to any constituent of the study drug. 2. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk. 3. Planned or expected vaccination with live attenuated vaccines during the Treatment Period, or vaccination expected within 5 half-lives (4 months) of AK002 administration. 4. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study. 5. Any other reason that, in the opinion of the Investigator or Medical Monitor, makes the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | Through study completion, up to 21 months | Adverse events assessed using the CTCAE version 5.0. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Tissue Eosinophil Responders | At Follow-up EGD (Esophago-Gastro-Duodenoscopy) (Day 505 or 28 days after last dose if ET) | A tissue eosinophil responder is defined as mean eosinophil count ≤4 cells/HPF in 5 gastric HPFs for EG only patients, ≤15 cells/HPF in 3 duodenal HPFs for EoD only patients, and ≤4 cells/HPF in 5 gastric HPFs and ≤15 cells/HPF in 3 duodenal HPFs for EG+EoD patients. |
| Change in PRO Total System Score (TSS) From AK002-016/AK002-012 Baseline | Main Study Baseline to Extension Weeks 71-72 | The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less-severe symptoms. |
Countries
United States
Participant flow
Recruitment details
The participants who were enrolled in and completed the studies AK002-016 (NCT04322604) or AK002-012 had the option to participate in this open-label extension study.
Participants by arm
| Arm | Count |
|---|---|
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) Subjects in this arm received the placebo in the main study and were treated with up to 18 monthly doses (3mg/kg) of lirentelimab (AK002).
lirentelimab: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8. | 75 |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) Subjects in this arm received the active drug in the main study and were treated with up to 18 monthly doses (3mg/kg) of lirentelimab (AK002).
lirentelimab: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8. | 84 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 11 |
| Overall Study | Elevation of ALT or AST | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 8 |
| Overall Study | Other | 3 | 5 |
| Overall Study | Physician Decision | 1 | 4 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 18 | 15 |
Baseline characteristics
| Characteristic | Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | Total | Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) |
|---|---|---|---|
| Age, Continuous | 42 years | 42 years | 42 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 23 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 136 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 66 Participants | 134 Participants | 68 Participants |
| Region of Enrollment United States | 75 Participants | 159 Participants | 84 Participants |
| Sex: Female, Male Female | 50 Participants | 103 Participants | 53 Participants |
| Sex: Female, Male Male | 25 Participants | 56 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 1 / 84 |
| other Total, other adverse events | 52 / 75 | 57 / 84 |
| serious Total, serious adverse events | 6 / 75 | 14 / 84 |
Outcome results
Primary
The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0
Adverse events assessed using the CTCAE version 5.0.
Time frame: Through study completion, up to 21 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Treatment-Related Adverse Events | 33 Participants |
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with an Adverse Event Leading to Study Drug Discontinuation | 6 Participants |
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Serious Adverse Events | 6 Participants |
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Treatment-Related Serious Adverse Events | 1 Participants |
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Adverse Events | 66 Participants |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Treatment-Related Serious Adverse Events | 1 Participants |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Adverse Events | 75 Participants |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Treatment-Related Adverse Events | 29 Participants |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with >=1 Serious Adverse Events | 14 Participants |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | The Safety and Tolerability of Lirentelimab by Evaluating Adverse Events Assessed Using the CTCAE Version 5.0 | No. of Subjects with an Adverse Event Leading to Study Drug Discontinuation | 10 Participants |
Other Pre-specified
Change in PRO Total System Score (TSS) From AK002-016/AK002-012 Baseline
The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less-severe symptoms.
Time frame: Main Study Baseline to Extension Weeks 71-72
Population: Number of participants with available data within Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | Change in PRO Total System Score (TSS) From AK002-016/AK002-012 Baseline | -14.4 score on a scale | Standard Deviation 11 |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | Change in PRO Total System Score (TSS) From AK002-016/AK002-012 Baseline | -17.0 score on a scale | Standard Deviation 12.1 |
Other Pre-specified
Proportion of Tissue Eosinophil Responders
A tissue eosinophil responder is defined as mean eosinophil count ≤4 cells/HPF in 5 gastric HPFs for EG only patients, ≤15 cells/HPF in 3 duodenal HPFs for EoD only patients, and ≤4 cells/HPF in 5 gastric HPFs and ≤15 cells/HPF in 3 duodenal HPFs for EG+EoD patients.
Time frame: At Follow-up EGD (Esophago-Gastro-Duodenoscopy) (Day 505 or 28 days after last dose if ET)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study Placebo to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | Proportion of Tissue Eosinophil Responders | 52 Participants |
| Main Study Active to Extension Study 3.0 mg/kg of Lirentelimab (AK002) | Proportion of Tissue Eosinophil Responders | 48 Participants |