A Phase 3 Multi-center, Open-label Study to Evaluate the Efficacy and Safety of Lanadelumab (SHP643) in Japanese Subjects With Hereditary Angioedema

Shire12 sites in 1 country12 target enrollmentDecember 12, 2019

ConditionsHereditary Angioedema (HAE)

InterventionsLanadelumab

DrugsLanadelumab

Overview

Phase: Phase 3
Intervention: Lanadelumab
Conditions: Hereditary Angioedema (HAE)
Sponsor: Shire
Enrollment: 12
Locations: 12
Primary Endpoint: Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of Day 0 Through Day 182
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this phase 3, open-label, multi-center study is to evaluate the safety and efficacy of lanadelumab in Japanese participants with HAE Type I or II.

Detailed Description

This study will consist of 52-week treatment period and a 4-week follow-up period. 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. After completion of treatment period B participants may roll over into an expanded access study TAK-743-5007 (NCT04687137). Participants who elect to rollover to Study TAK-743-5007 will complete their end of study (EOS) assessments on Day 378. All other participants will complete their EOS assessments on Day 392.

Registry

clinicaltrials.gov

Start Date

December 12, 2019

End Date

August 26, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shire

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
•The participant is male or female and \>= 12 years of age at the time of informed consent.
•Documented diagnosis of HAE (Type I or II) based upon all of the following:
•Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria).
•Diagnostic testing results obtained during screening that confirm HAE Type I or II: C1 inhibitor (C1-INH) functional level \<40% of the normal level. Participants with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. With prior sponsor approval, participants may be retested during the run-in period if results are in congruent with clinical history or believed by the investigator to be confounded by recent C1 inhibitor use.
•At least one of the following: age at reported onset of first angioedema symptoms \<=30 years, a family history consistent with HAE Type I or II, or C1q within normal range.
•Attack rate: Participants must experience at least 1 investigator-confirmed HAE attack per 4 weeks during the run-in period to enter the lanadelumab treatment period.
•The participant (or the participants parent/legal authorized representative, if applicable) has provided written informed consent approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
•If the participant is an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed or if the participant is a minor (ie, below the age of majority), have a parent/legally authorized representative who is informed of the nature of the study provide written informed consent (ie, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
•Males, or non pregnant, non lactating females who are fertile and sexually active and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study, or females of non child bearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or postmenopausal for at least 12 months.

Exclusion Criteria

•Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1-INH (also known as HAE Type 3), idiopathic angioedema, or recurrent angioedema associated with urticaria.
•Participation in a prior lanadelumab study.
•Dosing with investigational drug or exposure to an investigational device within 4 weeks prior to entering to screening.
•Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systematic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
•Exposure to androgens (eg, danazol, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period.
•Use of long-term prophylactic therapy for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) within 2 weeks prior to entering the run in period.
•Use of short-term prophylaxis for HAE 7 days prior to entering the run-in period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or anti-fibrinolytics used to avoid angioedema complications from medically indicated procedures.
•Any of the following liver function abnormalities: alanine aminotransferase (ALT) \>3x upper limit of normal, or aspartate aminotransferase (AST) \>3x upper limit of normal or bilirubin \>2x upper limit of normal (unless the bilirubin is a result of Gilbert's syndrome).
•Pregnancy or breast feeding.
•Participant has any condition that in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (eg, history of substance abuse, or dependence, significant preexisting illnesses or major comorbidity the investigator considers may confound the interpretation of the study results).

Arms & Interventions

Lanadelumab 300 mg q2w or q4w

Lanadelumab 300 mg solution, subcutaneously (SC), once every 2 weeks (q2w) for 26 weeks in Treatment Period A. This was followed by Treatment Period B (additional 26 weeks, total of 52 weeks including Treatment Period A) during which participants remained on Treatment Period A regimen or received 300 mg lanadelumab solution once every 4 weeks (q4w) for 26 weeks if well-controlled (attack-free) for 26 consecutive weeks with lanadelumab treatment. The dose frequency change was based on the Investigator's discretion and approval by the Sponsor's Medical Monitor.

Intervention: Lanadelumab

Outcomes

Primary Outcomes

Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of Day 0 Through Day 182

Time Frame: Day 0 through Day 182

A participant was considered as attack free during an efficacy evaluation period if the participant had no investigator-confirmed hereditary angioedema (HAE) attacks during that efficacy evaluation period. A HAE attack was 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). Number of participants achieving attack-free status for the efficacy evaluation period of Day 0 through Day 182 were assessed.

Secondary Outcomes

Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Participants Achieving Investigator-Confirmed Hereditary Angioedema (HAE) Attack-Free Intervals(Day 0 through Day 182)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs)(From first dose of the study drug up to end of study (EOS) (up to Day 392))
Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma(Predose on Days 0 (or Baseline), 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392)
Number of Participants With TEAEs Related to Electrocardiogram (ECG)(From first dose of the study drug up to end of study (EOS) (up to Day 392))
Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period(Day 70 through Day 182)
Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods(Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364)
Number of Participants Achieving Attack-Free Status for Monthly Increments(At Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13)
Plasma Concentrations of Lanadelumab(Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392)
Plasma Kallikrein (pKal) Activity(Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392)
Number of Participants With TEAEs Related to Clinical Laboratory Tests(From first dose of the study drug up to end of study (EOS) (up to Day 392))
Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364(Day 0 through Day 364, Day 70 through Day 182, and Day 70 through Day 364)
Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score(Days 0, 28, 56, 98, 126, 154, 182, 266, 364, 378 or 392)
Number of Participants With TEAEs Related to Vital Signs(From first dose of the study drug up to end of study (EOS) (up to Day 392))