Hereditary Angioedema
Conditions
Keywords
HAE, Angioedema
Brief summary
The goal of this clinical trial is to test the drug navenibart in participants with hereditary angioedema (HAE). One group of participants will get 1 dose of navenibart, and 2 other groups will get 2 doses of navenibart. Researchers will study the effects of navenibart in participants with HAE as this is the first time that the drug has been given to participants with HAE.
Detailed description
This is a Phase 1b/2 single and multiple dose trial evaluating the safety, tolerability, clinical activity, pharmacokinetics, pharmacodynamics, and immunogenicity of subcutaneous administration of navenibart in participants with type I or type II HAE in 3 dose cohorts. The first cohort will receive 1 dose of navenibart; the second and third cohorts will receive 2 sequential doses. This is the first trial of navenibart in participants with HAE and the first evaluation of a multiple-dose regimen. After the required follow up period, participants who are willing and eligible to consent can begin participation in the long-term open label extension study (STAR-0215-202, ALPHA-SOLAR; NCT06007677).
Interventions
DRUGNavenibart
Navenibart will be administered as a subcutaneous bolus injection.
Sponsors
Astria Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented diagnosis of HAE (type I or II). The following must be met: a. Documented clinical history consistent with HAE (for example, subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria). 2. Experienced at least 2 HAE attacks during the Run-In period, as confirmed by an investigator based on meeting the protocol-specified definition of an HAE attack.
Exclusion criteria
1. Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor deficiency, HAE with normal C1-INH (also known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria. 2. Use of therapies prescribed for the prevention of HAE attacks prior to Screening: 1. lanadelumab within 90 days 2. berotralstat within 21 days 3. all other prophylactic therapies, within 7 days 3. Any exposure to angiotensin-converting enzyme inhibitors or any estrogen containing medications with systemic absorption (such as hormonal contraceptives or hormone replacement therapy) within 28 days prior to Screening. 4. Any exposure to androgens (for example, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within 7 days prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Treatment-emergent Adverse Events | Day 1 through Day 448 (Cohort 1), Day 531 (Cohort 2), Day 475 (Cohort 3) | An adverse event was any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product that did not necessarily have a causal relationship with the treatment. A treatment-emergent adverse event was defined as any adverse event with an onset at the time of or following the start of treatment with study drug, or medical conditions present before the start of treatment that increased in severity or relationship at the time of or following the start of treatment. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Monthly Hereditary Angioedema (HAE) Attack Rate | Baseline, Day 168 (Cohort 1), Day 251 (Cohort 2), Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The HAE attack rate was the number of unique investigator-confirmed HAE attacks per month. |
| Number of Participants Who Were HAE Attack Free | Baseline through Day 168 (Cohort 1), Day 251 (Cohort 2), Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). |
| Severity of HAE Attacks Experienced by Participants | Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). All HAE attacks were classified by the investigator according to severity: mild (transient or mild discomfort); moderate (mild to moderate limitation in activity, some assistance with daily activities needed); severe (marked limitation in activity, assistance with daily activities required). |
| Duration of HAE Attacks | Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). |
| Number of HAE Attacks Requiring On-demand Therapy | Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). |
| Time to First HAE Attack After First and Last Dosing | Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The time to first HAE attack was calculated by: (\[First HAE attack or censor date\] - First Treatment date) +1. If a participant did not have an HAE attack, they were censored to the end of study date. |
| Proportion of HAE Attack-free Days | Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3) | An attack was considered an HAE attack if at least 1 of the following criteria was met (per the investigator): peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region); abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea); laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The proportion of HAE attack-free days was calculated by: (the number of HAE attack-free days/duration of evaluation period in days). |
| Maximum Drug Concentration (Cmax) of Navenibart | Day 1 (pre-dose, 4 hours post dose) up to Day 168 (Cohort 1); Day 1 (pre-dose, 4 hours post dose) up to Day 251 (Cohort 2); Day 1 (pre-dose, 4 hours post dose) up to Day 195 (Cohort 3) | Blood samples were collected at designated timepoints to measure the Cmax of navenibart. Results reported as micrograms/milliliter (mcg/mL). |
| Percent Change From Baseline in Plasma Levels of Cleaved High-molecular-weight Kininogen (cHMWK) | Baseline, Day 56 (Cohort 1), Day 90 (Cohort 2), Day 41 (Cohort 3) | Blood samples were collected to measure the plasma levels of cHMWK (a measure of plasma kallikrein activity). Results reported as percent change in percentage cHMWK (%cHMWK). A decrease in %cHMWK is reflective of the pharmacodynamic activity of navenibart. |
| Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Navenibart | Day 1 (pre-dose) up to Day 168 (Cohort 1); Day 1 (pre-dose) up to Day 251 (Cohort 2); Day 1 (pre-dose) up to Day 195 (Cohort 3) | Blood samples were collected at designated timepoints to assess the formation of navenibart ADAs in serum. |
Countries
Bulgaria, Canada, Czechia, Germany, United Kingdom, United States
Participant flow
Recruitment details
Of the 41 participants who were recruited and screened, 29 participants were enrolled and received navenibart (STAR-0215). All enrolled participants who received navenibart were included in the safety, efficacy, pharmacokinetics, and pharmacodynamics analyses.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.9 Years STANDARD_DEVIATION 17.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 4 / 4 | 9 / 13 | 12 / 12 |
| serious Total, serious adverse events | 0 / 4 | 0 / 13 | 0 / 12 |
Outcome results
None listed