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.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Navenibart will be administered as a subcutaneous bolus injection.
Allervie Clinical Research
Birmingham, Alabama, United States
Number of Participants Experiencing Treatment-emergent Adverse Events
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.
Time frame: Day 1 through Day 448 (Cohort 1), Day 531 (Cohort 2), Day 475 (Cohort 3)
Percent Change From Baseline in Monthly Hereditary Angioedema (HAE) Attack Rate
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.
Time frame: Baseline, Day 168 (Cohort 1), Day 251 (Cohort 2), Day 195 (Cohort 3)
Number of Participants Who Were HAE Attack Free
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 frame: Baseline through Day 168 (Cohort 1), Day 251 (Cohort 2), Day 195 (Cohort 3)
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Medical Research of Arizona a Division of Allergy, Asthma & Immunology Associates, LTD.
Scottsdale, Arizona, United States
Allergy & Asthma Clinic of Northwest Arkansas
Bentonville, Arkansas, United States
Acuro Research, Inc.
Little Rock, Arkansas, United States
UC San Diego US HAEA Angioedema Center
San Diego, California, United States
Raffi Tachdjian MD, Inc
Santa Monica, California, United States
Allergy & Asthma Clinical Research
Walnut Creek, California, United States
Institute for Asthma and Allergy, PC
Chevy Chase, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Washington University School of Medicine
St Louis, Missouri, United States
...and 10 more locations
Severity of HAE Attacks Experienced by Participants
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).
Time frame: Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Duration of HAE Attacks
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 frame: Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Number of HAE Attacks Requiring On-demand Therapy
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 frame: Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Time to First HAE Attack After First and Last Dosing
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.
Time frame: Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Proportion of HAE Attack-free Days
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).
Time frame: Day 1 through Day 168 (Cohort 1), Day 251 (Cohort 2), and Day 195 (Cohort 3)
Maximum Drug Concentration (Cmax) of Navenibart
Blood samples were collected at designated timepoints to measure the Cmax of navenibart. Results reported as micrograms/milliliter (mcg/mL).
Time frame: 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)
Percent Change From Baseline in Plasma Levels of Cleaved High-molecular-weight Kininogen (cHMWK)
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.
Time frame: Baseline, Day 56 (Cohort 1), Day 90 (Cohort 2), Day 41 (Cohort 3)
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Navenibart
Blood samples were collected at designated timepoints to assess the formation of navenibart ADAs in serum.
Time frame: 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)