Hereditary AngioedemaPhase 3SPRINGNCT04070326
A Study of Lanadelumab to Prevent Hereditary Angioedema (HAE) Attacks in Children
A Phase 3 study testing Lanadelumab in people with Hereditary Angioedema, run by Shire at 17 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 11 years
- Conditions the study is for
- Hereditary Angioedema
- 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
- 21 participants
- Where
- 17 sitesin 5 countries
- Study dates
- 19 Aug 2019to 30 Oct 2021
- 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 2 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
17 sites in 5 countries.
17 sites in 5 countries
United States11 sites
Hudson-Essex Allergy
Belleville, New Jersey, 07109
IMMUNOe Research Centers
Centennial, Colorado, 80112
Clinical Research Center of Charlotte
Charlotte, North Carolina, 28277
Institute Asthma and Allergy
Chevy Chase, Maryland, 20815
Bernstein Clinical Research Center
Cincinnati, Ohio, 45231
AARA Research Center
Dallas, Texas, 75231
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
AIRE Medical of Los Angeles
Santa Monica, California, 90404
Washington University School of Medicine
St Louis, Missouri, 63110
Toledo Institute of Clinical Research Asthma & Allergy Center
Toledo, Ohio, 43617
Allergy & Asthma Clinical Research
Walnut Creek, California, 94598
Germany3 sites
Charité - Universitätsmedizin Berlin.
Berlin, 10117
Klinikum der Johann-Wolfgang Goethe-Universitat.
Frankfurt, 60590
Hämophilie Zentrum Rhein Main GmbH
Mörfelden-Walldorf, 64546
About this study
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
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.
Read the 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
- Being tested
- Lanadelumab
- Keywords
- 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 TAK-743, DX-2930, SHP643
Participants will receive 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week treatment period.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Lanadelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: Up to approximately 115 weeks
Plasma Concentrations of Lanadelumab Over The Treatment Period
The plasma concentration of lanadelumab over treatment period was assessed.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Normalized number of investigator-confirmed HAE attacks during overall period are expressed as a monthly HAE attack rate. Investigator-confirmed HAE attack rate was calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is defined as the symptoms or signs consistent with an attack in >=1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Measured: 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
Normalized number of investigator-confirmed HAE attacks during each efficacy evaluation period other than overall treatment period are expressed as a monthly HAE attack rate. Investigator-confirmed HAE attack rate was calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28 days. A HAE attack is defined as symptoms or signs consistent with an attack in at least 1 of following locations: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Measured: 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
Time to first investigator-confirmed HAE attack (days) for each efficacy evaluation period was calculated from date and time of first dose of lanadelumab for that efficacy evaluation period to date and time of first investigator-confirmed HAE attack after first open-label dose for that efficacy evaluation period. A HAE attack is defined as symptoms or signs consistent with an attack in >=1 of following locations: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of tongue, palate, uvula, or larynx). Kaplan-Meier Method was used for analysis.
Measured: 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
The normalized number of investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as a monthly HAE attack rate. The investigator-confirmed HAE attack rate was calculated for each participant as the number of investigator-confirmed HAE attacks occurring during the given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Measured: 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
The normalized number of moderate or severe investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as a monthly HAE attack rate. The investigator-confirmed HAE attack rate was calculated for each participant as the number of investigator-confirmed HAE attacks occurring during the given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Measured: 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 High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
The normalized number of high morbidity investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as a monthly HAE attack rate. The investigator-confirmed HAE attack rate was calculated for each participant as the number of investigator-confirmed HAE attacks occurring during the given study period divided by the number of days the participant contributed to the period multiplied by 28 days. A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Measured: 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
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
Characteristics of investigator-confirmed HAE attacks for each efficacy evaluation period included duration, severity, attack location, and rescue medication use. A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Only categories with data are reported.
Measured: 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
Number of Participants With HAE Attack-Free Status for Each Evaluation Period
A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx).
Measured: 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
Plasma Kallikrein (pKal) Activity
pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics of lanadelumab.
Measured: Day 0 (Pre-dose), at any time on Days 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
Number of Participants With Immunogenicity Status as Positive or Negative
Immunogenicity was measured based on the presence or absence of neutralizing or non-neutralizing Anti-drug Antibody (ADA) in plasma.
Measured: Day 0 (Pre-dose), Days 28, 84, 140, 182, 196, 252, 308, 364 and 392
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start19 Aug 2019
- Primary completion30 Oct 2021
- Study completion30 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04070326
- Sponsor's protocol ID
- SHP643-301
- Other IDs
- 2018-002093-42, 2018
- Acronym
- SPRING
- Status last verified
- Apr 2022
- First submitted
- 26 Aug 2019
- Last updated
- 26 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- 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.
Publications
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.
PubMed 37730089
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04070326
- Acronym / sponsor ID
- SPRING / SHP643-301
- Conditions
- Hereditary Angioedema
- Keywords
- Lanadelumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2019 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 30 Oct 2021 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Posted 26 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lanadelumab 150 mg: Age 2 to <6 Years | Experimental | Drug: LanadelumabParticipants 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). |
| Lanadelumab 150 mg: Age 6 to <12 Years | Experimental | Drug: LanadelumabParticipants 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. |
Who may qualify
- Ages
- 2 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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:
- 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).
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LanadelumabAlso: TAK-743, DX-2930, SHP643Participants will receive 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week treatment period. | Drug | Lanadelumab 150 mg: Age 2 to <6 Years, Lanadelumab 150 mg: Age 6 to <12 Years |
Primary outcome
Number of Participants With Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Time frame: Up to approximately 115 weeks
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).
Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
Time frame: Up to approximately 115 weeks
Laboratory values (chemistry, hematology, and coagulation) were to be considered clinically significant based on investigator's discretion.
Number of Participants With Clinically Significant Vital Signs Measurements
Time frame: Up to approximately 115 weeks
Vital signs included blood pressure, heart rate, body temperature, and respiratory rate.
Plasma Concentrations of Lanadelumab Over The Treatment Period
Time frame: Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
The plasma concentration of lanadelumab over treatment period was assessed.
Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
10 secondary outcomes
Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
Time frame: 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
Number of Participants With Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period
Time frame: 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
Number of Participants With HAE Attack-Free Status for Each Evaluation Period
Time frame: 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
Plasma Kallikrein (pKal) Activity
Time frame: Day 0 (Pre-dose), at any time on Days 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
Number of Participants With Immunogenicity Status as Positive or Negative
Time frame: Day 0 (Pre-dose), Days 28, 84, 140, 182, 196, 252, 308, 364 and 392
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37730089Maurer 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.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
17 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lanadelumab in people with Hereditary Angioedema, run by Shire at 17 sites in 5 countries.
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 8 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 26 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Germany, Canada, Hungary, Spain. 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 26 May 2022). 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 Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) (time frame: Up to approximately 115 weeks). The study lists 12 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 NCT04070326, which also lists 1 linked publication.
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 26 May 2022.