Clinical trial NCT04070326: A Study of Lanadelumab to Prevent Hereditary Angioedema (HAE) Attacks in Children
Official title: SPRING STUDY: An Open-Label, Multicenter, Phase 3 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab for Prevention Against Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects 2 to <12 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: Lanadelumab
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.
* 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.

Primary outcomes:
measure: Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to approximately 115 weeks
measure: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
timeFrame: Up to approximately 115 weeks
measure: Number of Participants With Clinically Significant Vital Signs Measurements
timeFrame: Up to approximately 115 weeks
measure: Plasma Concentrations of Lanadelumab Over The Treatment Period
timeFrame: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
measure: Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma
timeFrame: 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
measure: Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma
timeFrame: 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
measure: Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma
timeFrame: 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
measure: Time to Reach Maximum Observed Concentration (Cmax) [Tmax] of Lanadelumab in Plasma
timeFrame: 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
measure: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma
timeFrame: 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
measure: Terminal Half-life (t1/2) of Lanadelumab in Plasma
timeFrame: 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
measure: Apparent Clearance (CL/F) of Lanadelumab
timeFrame: 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
measure: Apparent Volume of Distribution (V/F) of Lanadelumab
timeFrame: 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:
measure: Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period
timeFrame: Day 0 (after start of study drug administration) through Day 364 (Week 52)
measure: Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period
timeFrame: Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
measure: Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period
timeFrame: 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
measure: Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period
timeFrame: 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
measure: Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
timeFrame: 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
measure: Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
timeFrame: 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
measure: Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
timeFrame: 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
measure: Number of Participants With HAE Attack-Free Status for Each Evaluation Period
timeFrame: 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
measure: Plasma Kallikrein (pKal) Activity
timeFrame: Day 0 (Pre-dose), at any time on Days 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
measure: Number of Participants With Immunogenicity Status as Positive or Negative
timeFrame: Day 0 (Pre-dose), Days 28, 84, 140, 182, 196, 252, 308, 364 and 392
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: AIRE Medical of Los Angeles
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Chevy Chase
country: United States
facility: Institute Asthma and Allergy
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Belleville
country: United States
facility: Hudson-Essex Allergy
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Charlotte
country: United States
facility: Clinical Research Center of Charlotte
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research Asthma & Allergy Center
state: Ohio
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Ottawa
country: Canada
facility: Yang Medicine
state: Ontario
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin.
city: Frankfurt
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe-Universitat.
city: Mörfelden-Walldorf
country: Germany
facility: Hämophilie Zentrum Rhein Main GmbH
city: Budapest
country: Hungary
facility: Semmelweis Egyetem.
city: Madrid
country: Spain
facility: Hospital Universitario La Paz. Paseo de la Castellana
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: