Efficacy and Safety of Lanadelumab (SHP643) in Japanese Participants With Hereditary Angioedema (HAE)

NCT04180163 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: SHP643-302195014
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 12

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.

Conditions

Hereditary Angioedema (HAE)

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of 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.

  Day 0 through Day 182

Secondary Outcomes (21)

• 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 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 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 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 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

Study Arms (1)

Lanadelumab 300 mg q2w or q4w

EXPERIMENTAL

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.

Drug: Lanadelumab

Interventions

Lanadelumab DRUG

Lanadelumab solution, SC

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

Lanadelumab 300 mg q2w or q4w

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Agree to adhere to the protocol-defined schedule of assessments and procedures.

You may not qualify if:

• 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).
• Participant has a known hypersensitivity to the IP or its components.

Sponsors & Collaborators

• Shire: lead

Study Sites (12)

Toyohashi Municipal Hospital

Toyohashi, Aichi-ken, 441-8570, Japan

Location

Asahi General Hospital

Asahi-shi, Chiba, 289-2511, Japan

Location

Ogaki Municipal Hospital

Ogaki-shi, Gifu, 503-8502, Japan

Location

Hiroshima University Hospital

Hiroshima, Hiroshima, 734-8551, Japan

Location

Tomakomai City Hospital

Tomakomai-shi, Hokkaido, 053-8567, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Tokai University Hospital

Isehara-shi, Kanagawa, 259-1193, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

Kyoto University Hospital

Kyoto, Kyoto, 606-8507, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Saiyu Soka Hospital

Soka-shi, Saitama, 340-0041, Japan

Location

Shimane University Hospital

Izumo-shi, Shimane, 693-8501, Japan

Location

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 27, 2019
• Study Start: December 12, 2019
• Primary Completion: August 26, 2021
• Study Completion: August 26, 2021
• Last Updated: September 30, 2022
• Results First Posted: September 19, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

JP (12)