A Study of Lanadelumab (SHP643) in Chinese Participants With Hereditary Angioedema (HAE)

NCT05460325 | Completed Phase 3 Results

• 1 other identifier: SHP643-304
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

The main aim of this study is to evaluate the safety of lanadelumab in Chinese participants with HAE. Participants will be treated with lanadelumab for 26 weeks.

Conditions

Hereditary Angioedema (HAE)

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

  TEAE is defined as an adverse event (AE) with onset at the time of or following initial dosing with study drug (lanadelumab), or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. An 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. Hypersensitivity reactions and events of disordered coagulation were considered as AESIs. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly in this outcome measure. A participant could be counted in more than one category.

  From first dose of study drug up to end of study (up to Day 210)

• Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters

  Laboratory parameters included clinical chemistry, hematology, coagulation, urinalysis, and serology. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters (including clinical chemistry, hematology, coagulation, urinalysis, and serology) were reported.

  From first dose of study drug up to end of study (up to Day 210)

• Number of Participants With Clinically Meaningful Changes in Vital Sign Abnormalities

  Vital signs included measurement of blood pressure, heart rate, body temperature, and respiratory rate. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in vital signs were reported.

  From first dose of study drug up to end of study (up to Day 210)

• Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)

  ECG included heart rate, PR interval, QRS duration, QT interval, corrected QT interval (QTc) interval, QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval, and QT corrected for heart rate by Bazett formula (QTcB) interval. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in ECG were reported.

  From first dose of study drug up to end of study (up to Day 210)

• Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182

  Physical examination findings by body system were classified as height and weight, general appearance, ears, nose and throat, head and neck, ophthalmological, respiratory, cardiovascular, abdomen, neurological, extremities, dermatological, and lymphatic. Number of participants with clinically significant changes in physical examination findings per investigator interpretation were reported. Only categories with at least one participant with event are reported.

  Day 182

Secondary Outcomes (14)

• Plasma Concentrations of Lanadelumab

  Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182

• Plasma Kallikrein (pKal) Activity

  Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182

• Number of Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182

  Day 0 through Day 182

• Number of Investigator-Confirmed HAE Attacks That Required Acute Treatment During the Efficacy Evaluation Period of Day 0 Through Day 182

  Day 0 through Day 182

• Number of Moderate or Severe Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182

  Day 0 through Day 182

Study Arms (1)

Lanadelumab 300 mg

EXPERIMENTAL

Participants received lanadelumab 300 milligrams (mg), subcutaneously (SC), once every 2 weeks (Q2W) from Day 0 to Day 182 (26 weeks).

Drug: Lanadelumab

Interventions

Lanadelumab DRUG

Lanadelumab subcutaneous injection

Also known as: SHP643, TAKHZYRO, TAK-743, DX-2930, Lanadelumab Injection

Lanadelumab 300 mg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be of Chinese descent, defined as born in China and having Chinese parents and Chinese maternal and paternal grandparents.
• The participant is male or female and greater than or equal to (\>=) 12 years of age at the time of informed consent.
• Documented diagnosis of HAE Type I or Type II based upon all of the following:
• Documented clinical history consistent with HAE (subcutaneous \[SC\] or mucosal, nonpruritic swelling episodes without accompanying urticaria).
• Diagnostic testing results obtained during screening by a laboratory (approved by the sponsor) that confirm HAE Type I or Type II: C1 esterase inhibitor (C1-INH) functional level \<40% of the normal level. Participants with functional C1-INH level 40% to 50% of the normal level may be enrolled if they also have a C4 level below the normal range. Participants may begin participating in the run-in period before these diagnostic results are available. Participants may be re-tested if results are incongruent with clinical history or believed by the investigator to be confounded by recent long-term prophylaxis (LTP) use.
• At least one of the following: Age at reported onset of first angioedema symptoms less than or equal to (\<=) 30 years, a family history consistent with HAE Type I or Type II, or C1q within normal range.
• Attack rate:
• At the time of enrollment, participants must experience at least 1 investigator-confirmed HAE attack per 4 weeks during the run-in period.
• The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board (IRB)/ institutional ethical committee (IEC).
• If the participant is an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
• If the participant is a minor (that is \<18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (that is, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
• Males, or non-pregnant, non-lactating females who are fertile and sexually active 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 postmenopausal for at least 12 months.
• Agree to adhere to the protocol-defined schedule of assessments and procedures.

You may not qualify if:

• Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema, HAE with normal C1 esterase inhibitor (C1-INH) (also known as HAE Type III), idiopathic angioedema, or recurrent angioedema associated with urticaria.
• Participation in a prior lanadelumab study or use any lanadelumab prior to the study.
• Dosing with investigational drug or exposure to an investigational device within 4 weeks prior to entering to screening.
• Exposure to angiotensin-converting enzyme inhibitors or any estrogen-containing medications with systematic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
• Exposure to androgens (that is, danazol, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period.
• Use of LTP therapy (defined as continued use) for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) for adult participants within 2 weeks prior to entering the run-in period. Adolescent participants (\>=12 to \<18 years of age) who are on LTP therapy for HAE are allowed to enter the study.
• Use of short-term prophylaxis for HAE 7 days prior to entering the run-in period. Short-term prophylaxis is defined as fresh frozen plasma (FFP), C1-INH, attenuated androgens, or antifibrinolytics used to avoid angioedema complications from medically indicated procedures. Note: Currently, C1-INH therapies are not available in China.
• Any of the following liver function abnormalities: alanine aminotransferase (ALT) greater than (\>) 3\* upper limit of normal (ULN), or aspartate aminotransferase (AST) \> 3\* ULN or bilirubin \> 2\* ULN (unless the bilirubin is a result of Gilbert's syndrome).
• Pregnancy or breast feeding.
• Participant has any condition that in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (example, history of substance abuse or dependence, significant pre-existing illnesses or major comorbidity the investigator considers may confound the interpretation of the study results).

Sponsors & Collaborators

• Takeda: lead

Study Sites (4)

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510260, China

Location

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

Location

Yantai Yuhuangding Hospital

Yantai, Shandong, 264000, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

lanadelumab

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 15, 2022
• Study Start: June 22, 2022
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: December 13, 2024
• Results First Posted: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

CN (4)