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

Shire21 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Hereditary Angioedema

Interventions

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

Eligibility

Sex: ALLMin age: 2 YearsMax age: 11 Years

Medical Language ↔ Plain English

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. * A historical baseline HAE attack rate of at least 1 attack per 3 months. Note: In addition, participants who experience greater than or equal to (\>=)1.0 angioedema attacks per three months during the 12-week baseline observation period and who remain eligible per the inclusion criteria will enter the lanadelumab treatment period. * 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.

Locations (17)

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

...and 7 more locations

Outcomes

Primary Outcomes

Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this 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 which results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, is an important medical event. Adverse events of special interest for this study are hypersensitivity reactions and disordered coagulation (hypercoagulability events and bleeding events).

Time frame: Up to approximately 115 weeks

Number of Participants With Clinically Significant Laboratory Assessment Abnormalities

Laboratory values (chemistry, hematology, and coagulation) were to be considered clinically significant based on investigator's discretion.

Time frame: Up to approximately 115 weeks

Number of Participants With Clinically Significant Vital Signs Measurements

Vital signs included blood pressure, heart rate, body temperature, and respiratory rate.

Time frame: Up to approximately 115 weeks

Plasma Concentrations of Lanadelumab Over The Treatment Period

The plasma concentration of lanadelumab over treatment period was assessed.

Time frame: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma