A Study of Lanadelumab to Prevent Hereditary Angioedema (HAE) Attacks in Children

NCT ID: NCT04070326

Last Updated: 2022-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-19
• Study Completion Date: 2021-10-30

Brief Summary

The main aims of this study are to learn how lanadelumab moves through a child's body and if the children have any medical problems from lanadelumab. Other aims are to learn if prophylactic treatment with lanadelumab reduces the number and severity of HAE attacks in children, how lanadelumab affects the child's body, and if the children develop antibodies to lanadelumab.

The study doctors will treat acute HAE attacks according to their standard practice.

Participants will receive lanadelumab for up to 52 weeks. When they start treatment, participants will visit their clinic every week for the first 4 weeks. Then, they will visit their clinic every 4 weeks during treatment.

Detailed Description

This study will consists of 52-week treatment period and a 2 or 4-weeks follow-up period (depending on the treatment schedule). 52-week treatment period comprises of a 26-week treatment period A (Day 0 to Day 182) and a 26-week treatment period B (Day 183 to Day 364). Participants who complete treatment period A will immediately continue into treatment period B.

Conditions

Hereditary Angioedema

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Lanadelumab 150 mg: Age 2 to <6 Years

Participants aged 2 to \<6 years received lanadelumab subcutaneous (SC) injection at a dose of 150 milligrams (mg) for every 4 weeks (q4wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).

Group Type: EXPERIMENTAL

Lanadelumab

Intervention Type: DRUG

Participants will receive 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week treatment period.

Lanadelumab 150 mg: Age 6 to <12 Years

Participants aged 6 to \<12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator's discretion and sponsor's medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.Participants aged 6 to \<12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator's discretion and sponsor's medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.

Group Type: EXPERIMENTAL

Lanadelumab

Intervention Type: DRUG

Participants will receive 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week treatment period.

Interventions

Lanadelumab

Participants will receive 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week treatment period.

Intervention Type: DRUG

Other Intervention Names

TAK-743; DX-2930; SHP643

Eligibility Criteria

Inclusion Criteria

• Be a child (male or female) 2 to lesser than (<) 12 years of age at the time of screening.
• Documented diagnosis of HAE (Type I or II) based upon both of the following:

1. Documented clinical history consistent with HAE (SC or mucosal, nonpruritic swelling episodes without accompanying urticarial).

2. Diagnostic testing results obtained during screening from a sponsor- approved central laboratory that confirm C1-INH functional level < 40 percent (%) of the normal level. Participants with functional C1 esterase inhibitor (C1-INH) level 40-50% of the normal level may be enrolled if they also have a complement4 (C4) level below the normal range. With prior sponsor approval, participants may be retested during the baseline observation period if results are incongruent with clinical history or believed by the investigator to be confounded by recent complement1 (C1) inhibitor use.

• Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
• Have a parent(s)/legal guardian who is informed of the nature of the study and can provide written informed consent for the child to participate in the study before any study-specific procedures are performed (with assent from the child when appropriate).
• Females of childbearing potential must agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol through the duration of the study from screening through 70 days after the final study visit.

Exclusion Criteria

• Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1-INH, idiopathic angioedema, or recurrent angioedema associated with urticaria.
• Dosing with an investigational drug or exposure to an investigational device within 4 weeks prior to screening.
• Be pregnant or breastfeeding.
• Have initiated androgen treatment (eg, stanozolol, danazol, oxandrolone, methyltestosterone, and testosterone) within 2 weeks prior to entering the observation period.
• Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
• Have any active infectious illness or fever defined as an oral temperature greater than (>) 38 degree celsius (°C) (100.4 fahrenheit [°F]), tympanic > 38.5°C (101.3°F) , axillary > 38°C (100.4°F), or rectal/core > 38.5°C (101.3°F) within 24 hours prior to the first dose of study drug in treatment period A.
• Have any HAE attack that is not resolved prior to the first dose of study drug in treatment period A.
• Have any of the following liver function test abnormalities: alanine aminotransferase (ALT) > 3*upper limit of normal (ULN), or aspartate aminotransferase (AST) > 3*ULN, or total bilirubin > 2*ULN (unless the bilirubin elevation is a result of Gilbert's syndrome).
• Have any condition (any surgical or medical condition) 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 (eg, significant pre-existing illness or other major comorbidity that the investigator considers may confound the interpretation of study results).
• Participant has a known hypersensitivity to the investigational product or its components.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

AIRE Medical of Los Angeles

Santa Monica, California, United States

Allergy & Asthma Clinical Research

Walnut Creek, California, United States

IMMUNOe Research Centers

Centennial, Colorado, United States

Institute Asthma and Allergy

Chevy Chase, Maryland, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hudson-Essex Allergy

Belleville, New Jersey, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Clinical Research Center of Charlotte

Charlotte, North Carolina, United States

Bernstein Clinical Research Center

Cincinnati, Ohio, United States

Toledo Institute of Clinical Research Asthma & Allergy Center

Toledo, Ohio, United States

AARA Research Center

Dallas, Texas, United States

Yang Medicine

Ottawa, Ontario, Canada

Charité - Universitätsmedizin Berlin.

Berlin, , Germany

Klinikum der Johann-Wolfgang Goethe-Universitat.

Frankfurt, , Germany

Hämophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, , Germany

Semmelweis Egyetem.

Budapest, , Hungary

Hospital Universitario La Paz. Paseo de la Castellana

Madrid, , Spain

Countries

United States; Canada; Germany; Hungary; Spain

References

Maurer M, Lumry WR, Li HH, Aygoren-Pursun E, Busse PJ, Jacobs J, Nurse C, Ahmed MA, Watt M, Yu M; SPRING Investigators. Lanadelumab in Patients 2 to Less Than 12 Years Old With Hereditary Angioedema: Results From the Phase 3 SPRING Study. J Allergy Clin Immunol Pract. 2024 Jan;12(1):201-211.e6. doi: 10.1016/j.jaip.2023.09.009. Epub 2023 Sep 18.

Reference Type: DERIVED

PMID: 37730089 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Original Protocol

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b5fdc4db2bf003ab472e6

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

Other Identifiers

2018-002093-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SHP643-301

Identifier Type: -

Identifier Source: org_study_id