A Study of Long-Term Safety and Efficacy of Lanadelumab for Prevention of Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the long-term safety and efficacy of repeated subcutaneous (SC) administration of lanadelumab in adolescents and adults with non-histaminergic angioedema with normal C1-inhibitor who completed study SHP643-303 (NCT04206605).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This study consists of 26-week treatment period (Day 0 to Day 182) and a 2-week follow-up period. Participants who completed the double-blind treatment period at Day 182 of Study SHP643-303 (NCT04206605) will enroll into this extension study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lanadelumab Rollover participants from SHP643-303 (NCT04206605) will receive 300 milligram (mg) of lanadelumab solution in prefilled syringe subcutaneously (SC) for 26 weeks once every 2 weeks (Q2W) or once every 4 weeks (Q4W) if well controlled during SHP643-303 (NCT04206605) with up to 13 doses. |
Drug: Lanadelumab
Rollover participants will receive 300 mg of lanadelumab solution in a PFS SC injection once Q2W or Q4W for 26 consecutive weeks.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) [From start of the study up to follow-up (Day 196)]
A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the investigational product or medicinal product. A SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.
Secondary Outcome Measures
- Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 [Day 0 through Day 182]
An angioedema attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: 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 investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.
- Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 [Day 0 through Day 182]
The overall severity of angioedema attack will be determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.
- Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 [Day 0 through Day 182]
A high morbidity angioedema attack is defined as any attack that has at least 1 of the following characteristics: severe, results in hospitalization (except hospitalization for observation less than (<) 24 hours), hemodynamically significant (systolic blood pressure less than < 90, requires intravenous (IV) hydration, or associated with syncope or near syncope) or laryngeal. Number of high-morbidity angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.
- Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab [Day 0, 84, 140 and 182]
Pharmacokinetic plasma concentrations of lanadelumab will be assessed.
- Plasma Kallikrein (pKal) Activity [Day 0, 84, 140 and 182]
Plasma Kallikrein activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK ) with factor XIIa activation level to assess pharmacodynamics of lanadelumab.
- Number of Participants With Positive Antidrug Antibodies (ADA) in Plasma [Day 0, 84, 140 and 182]
Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma will be assessed.
- Angioedema Quality of life (AE-QoL) Questionnaire [Day 0, 28, 84, 140 and 182]
The AE-QoL questionnaire is a self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema (including HAE). The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AE-QoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five-point response scale ranging from 1 (Never) to 5 (Very Often).
- Lanadelumab Injection Report During the Treatment Period of Day 0 Through Day 168 [Day 0 through Day 168]
An injection report will be completed by the participant (or parent/caregiver) following each dose administration of lanadelumab injection used during the treatment period of Day 0 through Day 168 will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males and females, 12 years of age and older diagnosed with non-histaminergic normal C1-INH angioedema at the time of enrollment into the antecedent Study SHP643-303 (NCT04206605).
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Participants must have completed the treatment period (through Visit 26/Day 182) of Study SHP643-303 (NCT04206605) without reporting a clinically significant TEAE that would preclude subsequent exposure to lanadelumab.
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Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
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Males, or non-pregnant, non-lactating females who are of child-bearing potential and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study; or females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months.
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The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board/research ethics board/ethics committee (IRB/REB/EC) at any time prior to study start. If the participant is a minor (i.e. lesser then (<) 18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (i.e. permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
Exclusion Criteria:
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Discontinued from Study SHP643-303 (NCT04206605) after enrollment but before Visit 26 for any reason.
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Presence of important safety concerns identified in Study SHP643-303 (NCT04206605) that would preclude participation in this study.
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Dosing with an investigational product (IP, not including IP defined in antecedent Study SHP643-303 [NCT04206605]) or exposure to an investigational device within 4 weeks prior to Day 0.
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Participants has a known hypersensitivity to the investigational product or its components.
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Have any condition (surgical or medical) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (e.g. significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Research Center of Alabama | Birmingham | Alabama | United States | 35209 |
| 2 | Medical Research of Arizona a division of Allergy, Asthma & Immunology Associates, LTD | Scottsdale | Arizona | United States | 85251 |
| 3 | UCSD Angioedema Center | San Diego | California | United States | 92122 |
| 4 | Asthma and Allergy Associates, PC | Colorado Springs | Colorado | United States | 80907 |
| 5 | Institute for Asthma & Allergy, P.C. | Chevy Chase | Maryland | United States | 20815 |
| 6 | University of Michigan Specialty Allergy Clinic and Food Allergy Clinic | Ann Arbor | Michigan | United States | 48106 |
| 7 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63414 |
| 8 | Optimed Research, LTD | Columbus | Ohio | United States | 43235 |
Sponsors and Collaborators
- Shire
- Takeda Development Center Americas, Inc.
Investigators
- Study Director: Study Director, Takeda Development Center Americas
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TAK-743-3001
- 2019-004823-20