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Hereditary Angioedema (HAE)Phase 3NCT05460325

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

A Phase 3 study testing Lanadelumab in people with Hereditary Angioedema (HAE), run by Takeda at 4 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Hereditary Angioedema (HAE)
What is being tested?
Lanadelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
4 sitesChina
Study dates
22 Jun 2022to 28 Nov 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • OR
  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

4 sites in 1 country.

China4 sites

  • Peking Union Medical College Hospital

    Beijing, 100730

  • The Second Affiliated Hospital of Guangzhou Medical University

    Guangzhou, Guangdong, 510260

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

    Wuhan, Hubei, 430030

  • Yantai Yuhuangding Hospital

    Yantai, Shandong, 264000

Other trials in China

About this study

Official title: A Multi-center, Open-label Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Lanadelumab (SHP643) in Chinese Subjects With Hereditary Angioedema

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.

Being tested
Lanadelumab
Medical subject headings
Angioedemas, Hereditary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LanadelumabDrug

    Also called SHP643, TAKHZYRO, TAK-743, DX-2930

    Lanadelumab subcutaneous injection

Study groups in NCT05460325
Study groupRoleWhat they receive
Lanadelumab 300 mgExperimentalParticipants received lanadelumab 300 milligrams (mg), subcutaneously (SC), once every 2 weeks (Q2W) from Day 0 to Day 182 (26 weeks).
Receives: Drug: Lanadelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

  5. 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.

    Measured: Day 182

Secondary outcomes (14)

  1. Plasma Concentrations of Lanadelumab

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

  2. Plasma Kallikrein (pKal) Activity

    pKal activity was measured by cleaved high molecular weight kininogen (cHMWK) level (i.e., plasma concentrations of cHMWK).

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

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

    An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.

    Measured: Day 0 through Day 182

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

    An HAE attack was confirmed by following symptoms/signs consistent with an attack in atleast one of the following locations:1)Peripheral angioedema:cutaneous swelling involving an extremity,the face,neck,torso,and/or genitourinary region;2)Abdominal angioedema:abdominal pain,with/without abdominal distention,nausea,vomiting,or diarrhea;3)Laryngeal angioedema:stridor,dyspnea, difficulty speaking,difficulty swallowing,throat tightening,or swelling of the tongue,palate,uvula,or larynx.Acute HAE attacks were managed per the investigator's usual care, including use of individualized acute therapy/rescue medications.Acute therapy/rescue medications included Firazyr, fresh frozen plasma (FFP), or other local standard of care.Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks requiring acute treatment occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.

    Measured: Day 0 through Day 182

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

    The severity of the investigator-confirmed HAE attacks was defined per the HAE attack assessment and reporting procedures (HAARP) definitions: severe (marked limitation in activity, assistance required), moderate (mild to moderate limitation in activity, some assistance needed). Treatment period attack rate per month is calculated as the number of moderate or severe investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days.

    Measured: Day 0 through Day 182

  6. Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182

    Number of participants with maximum HAE attack severity during the efficacy evaluation period was assessed. HAE attack severity was calculated per participant based on the severity categories as follows: No attack, Mild, Moderate, and Severe.

    Measured: Day 0 through Day 182

  7. Time to First Investigator-confirmed HAE Attack During the Efficacy Evaluation Period of Day 0 Through Day 182

    Time to the first investigator-confirmed HAE attack (days) was calculated from the date and time of the first dose of study drug for that efficacy evaluation period to the date and time of the first investigator-confirmed HAE attack after the first dose for the efficacy evaluation period. The time to the first HAE attack was summarized using Kaplan-Meier (KM) estimates.

    Measured: Day 0 through Day 182

  8. Number of Participants Who Achieved Investigator-confirmed HAE Attack-Free Status During the Efficacy Evaluation Period of Day 0 Through Day 182

    An HAE attack was confirmed by following symptoms or signs consistent with an attack in at least one of the following locations: 1) Peripheral angioedema: cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region; 2) Abdominal angioedema: abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea; 3) Laryngeal angioedema: stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx. A participant was considered as attack free if the participant had no investigator-confirmed HAE attacks during the efficacy evaluation period. Number of participants who achieved attack-free status for the efficacy evaluation periods were assessed.

    Measured: Day 0 through Day 182

  9. Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA

    A run-in period of 4 weeks was included to determine the participant's baseline attack rate. This period may be extended up to 8 weeks. The normalized number of investigator-confirmed HAE attacks during efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate relative to the run-in period NNA. Number of participants who achieved at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed NNA per 4 weeks relative to the run-in period normalized NNA for the efficacy evaluation periods was assessed.

    Measured: Day 0 through Day 182

  10. Number of Participants Who Achieved NNA <1.0 Per 4 Weeks for the Efficacy Evaluation Period of Day 0 Through Day 182

    The normalized number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a monthly (28 days) HAE attack rate. Attack rate was calculated for each participant as the number of attacks occurring during the specified period divided by the number of days the participant contributed to the specified period multiplied by 28 days. Number of participants who achieved NNA <1.0 per 4 weeks for the efficacy evaluation period were assessed.

    Measured: Day 0 through Day 182

  11. Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma

    Number of participants with neutralizing or non-neutralizing ADA in plasma were assessed.

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

  12. Plasma Concentrations of Lanadelumab by Immunogenicity Result

    The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the lanadelumab plasma concentrations was assessed.

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

  13. Plasma Kallikrein Activity cHMWK by Immunogenicity Result

    The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the cHMWK levels was assessed.

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

  14. Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182

    The number of investigator-confirmed HAE attacks during the efficacy evaluation period was expressed as a normalized monthly (4 weeks, i.e., 28 days). Treatment period attack rate per month is calculated as the number of investigator-confirmed HAE attacks occurring during that treatment period divided by number of days the participant contributed to that treatment period multiplied by 28 days. The effect of presence or absence of neutralizing or non-neutralizing ADA in plasma on the investigator-confirmed HAE attacks during the efficacy evaluation period was assessed.

    Measured: Day 0 through Day 182

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2022
  2. Study start22 Jun 2022
  3. Primary completion28 Nov 2023
  4. Study completion28 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05460325
Sponsor's protocol ID
SHP643-304
Status last verified
Dec 2024
First submitted
13 Jul 2022
Last updated
13 Dec 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lanadelumab in people with Hereditary Angioedema (HAE), run by Takeda at 4 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) (time frame: From first dose of study drug up to end of study (up to Day 210)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05460325.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.

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