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

NCT04070326 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: SHP643-3012018-002093-42
• Study Type: interventional
• Target: 21
• Locations: 5 countries
• Sites: 17

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.

Conditions

Hereditary Angioedema

Keywords

Lanadelumab

Outcome Measures

Primary Outcomes (12)

• 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).

  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.

  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.

  Up to approximately 115 weeks

• Plasma Concentrations of Lanadelumab Over The Treatment Period

  The plasma concentration of lanadelumab over treatment period was assessed.

  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

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Terminal Half-life (t1/2) of Lanadelumab in Plasma

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Apparent Clearance (CL/F) of Lanadelumab

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

• Apparent Volume of Distribution (V/F) of Lanadelumab

  Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392

Secondary Outcomes (10)

• Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period

  Day 0 (after start of study drug administration) through Day 364 (Week 52)

• Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period

  Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

• Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period

  Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

• Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period

  Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

• Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period

  Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364

Study Arms (2)

Lanadelumab 150 mg: Age 2 to <6 Years

EXPERIMENTAL

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).

Drug: Lanadelumab

Lanadelumab 150 mg: Age 6 to <12 Years

EXPERIMENTAL

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.

Drug: Lanadelumab

Interventions

Lanadelumab 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.

Also known as: TAK-743, DX-2930, SHP643

Lanadelumab 150 mg: Age 2 to <6 Years; Lanadelumab 150 mg: Age 6 to <12 Years

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (17)

AIRE Medical of Los Angeles

Santa Monica, California, 90404, United States

Location

Allergy & Asthma Clinical Research

Walnut Creek, California, 94598, United States

Location

IMMUNOe Research Centers

Centennial, Colorado, 80112, United States

Location

Institute Asthma and Allergy

Chevy Chase, Maryland, 20815, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hudson-Essex Allergy

Belleville, New Jersey, 07109, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Clinical Research Center of Charlotte

Charlotte, North Carolina, 28277, United States

Location

Bernstein Clinical Research Center

Cincinnati, Ohio, 45231, United States

Location

Toledo Institute of Clinical Research Asthma & Allergy Center

Toledo, Ohio, 43617, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Yang Medicine

Ottawa, Ontario, K1G6C6, Canada

Location

Charité - Universitätsmedizin Berlin.

Berlin, 10117, Germany

Location

Klinikum der Johann-Wolfgang Goethe-Universitat.

Frankfurt, 60590, Germany

Location

Hämophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, 64546, Germany

Location

Semmelweis Egyetem.

Budapest, 1125, Hungary

Location

Hospital Universitario La Paz. Paseo de la Castellana

Madrid, 28046, Spain

Location

Related Publications (1)

• 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.

  PMID: 37730089 DERIVED

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

ClinicalTransparency@takeda.com

+1 866 842 5335

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: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 28, 2019
• Study Start: August 19, 2019
• Primary Completion: October 30, 2021
• Study Completion: October 30, 2021
• Last Updated: May 26, 2022
• Results First Posted: May 26, 2022

Record last verified: 2022-04

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

HU (1); US (11); CA (1); ES (1); DE (3)