Long-term Safety and Efficacy Study of DX-2930 (SHP643) to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE

NCT ID: NCT02741596

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-26
• Study Completion Date: 2019-10-31

Brief Summary

This study is an open-label, long term safety and efficacy study to evaluate DX-2930 in preventing acute angioedema attacks in participants with Type I and Type II HAE.

Conditions

Hereditary Angioedema (HAE)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Rollover Participants

Participants who rollover from the DX-2930-03 study will receive 300 milligram (mg) DX-2930 subcutaneous injection at Day 0 followed by second dose following the first HAE attack and then once in every 2 weeks until the end of the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days is required between subsequent administrations.

Group Type: EXPERIMENTAL

DX-2930

Intervention Type: DRUG

Participants who rollover from the DX-2930-03 study will receive 300 milligram (mg) DX-2930 subcutaneous injection at Day 0 followed by second dose following the first HAE attack and then once in every 2 weeks until the end of the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days is required between subsequent administrations.

Non-rollover Participants

Participants who were not participants in DX-2930-03 will receive 300 milligram (mg) DX-2930 subcutaneous injection once in every 2 weeks until the end of the treatment period (up to 924 days).

Group Type: EXPERIMENTAL

DX-2930

Intervention Type: DRUG

Participants who were not participants in DX-2930-03 will receive 300 milligram (mg) DX-2930 subcutaneous injection once in every 2 weeks until the end of the treatment period (up to 924 days).

Interventions

DX-2930

Participants who rollover from the DX-2930-03 study will receive 300 milligram (mg) DX-2930 subcutaneous injection at Day 0 followed by second dose following the first HAE attack and then once in every 2 weeks until the end of the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days is required between subsequent administrations.

Intervention Type: DRUG

DX-2930

Participants who were not participants in DX-2930-03 will receive 300 milligram (mg) DX-2930 subcutaneous injection once in every 2 weeks until the end of the treatment period (up to 924 days).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female HAE participants who are 12 years of age or older at the time of screening
• Documented diagnosis of HAE (Type I or II) based on

1. Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria).

2. Diagnostic testing results obtained during screening (or a prior DX-2930 study) that confirm HAE Type I or II: C1 inhibitor (C1-INH) functional level less than (<) 40 percentage (%) 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. Participants may be retested if results are incongruent with clinical history or believed by the investigator to be confounded by long-term prophylactic (LTP) use. (It is understood that C1-INH therapy may alter the lab results of C1-INH assessments; therefore, the investigator's discretion in collaboration with Medical Monitor is advised for proper documentation of eligibility).

3. At least one of the following: Age at reported onset of first angioedema symptoms less than or equal to (<=) 30 years, a family history consistent with HAE Type I or II, or C1q within normal range.

• A historical baseline HAE attack rate of at least 1 attack per 12 weeks
• Adult participants and caregivers of participants under the age of 18 are willing and able to read, understand, and sign an informed consent form. Participants age 12 to 17, whose caregiver has provided informed consent, are willing and able to read, understand and sign an assent form.
• Males and females who are fertile and sexually active must adhere to contraception requirements for the duration of the study as

1. Females (NOTE: Female rollover participants (those who previously participated in Study DX-2930-03 [NCT02586805]) of childbearing potential may continue to use the birth control method used during Study DX-2930-03 (NCT02586805).) of childbearing potential must agree to be abstinent or it is recommended to use highly effective forms of contraception from the screening period through 30 days after the final study visit. This includes stable doses (for 3 months prior to study screening) of combined estrogen and progestin-containing hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), progestin-only hormonal contraception associated with inhibition of ovulation, intra-uterine device (IUD, all types) or intrauterine hormone releasing systems (IUS). Notes: 1) A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception. 2) Use of a male condom with or without spermicide or cervical cap, diaphragm or sponge with spermicide or a combination (double barrier methods) are not considered highly effective.

2. Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months do not require contraception during the study.

3. Males, including males who are surgically sterile (post vasectomy), with female partners of childbearing potential must agree to be abstinent or else use a medically acceptable form of contraception from the screening period through 60 days after the final study visit.

Exclusion Criteria

• Discontinued from DX-2930-03 (NCT02586805) after enrollment for any reason.
• If rolling over from DX-2930-03 (NCT02586805), presence of important safety concerns that would preclude participation in this study.
• Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1 inhibitor (also known as HAE Type III), idiopathic angioedema, or recurrent angioedema associated with urticaria.
• Dosing with an investigational drug (not including DX-2930 or other HAE therapies) or exposure to an investigational device within 4 weeks prior to screening.
• Exposure to angiotensin-converting enzyme (ACE) inhibitors within 4 weeks prior to screening or any newly initiated or dose modification of estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) 3 months prior to the screening visit.
• Unwilling to discontinue use of long-term prophylactic therapy for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) within 3 weeks after starting DX-2930 treatment.
• Any of the following liver function test abnormalities: alanine aminotransferase (ALT) > 3x upper limit of normal, or aspartate aminotransferase (AST) > 3x upper limit of normal, or total bilirubin > 2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert's Syndrome).
• Pregnancy or breastfeeding.
• 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, a significant pre-existing illness or other major comorbidity that the investigator considers may confound the interpretation of study results).

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Clinical Research Center of Alabama

Birmingham, Alabama, United States

Medical Research of Arizona

Scottsdale, Arizona, United States

University of California San Diego

San Diego, California, United States

AIRE Medical of Los Angeles

Santa Monica, California, United States

Allergy & Asthma Clinical Research

Walnut Creek, California, United States

IMMUNOe Research Centers

Centennial, Colorado, United States

Asthma and Allergy Associates, PC

Colorado Springs, Colorado, United States

University of South Florida

Tampa, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Institute Asthma and Allergy

Chevy Chase, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Midwest Immunology Clinic

Plymouth, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hudson-Essex Allergy, LLC

Belleville, New Jersey, United States

Atlantic Research Center, LLC

Ocean City, New Jersey, United States

Winthrop University Hospital

Mineola, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Clinical Research Center of Charlotte

Charlotte, North Carolina, United States

Duke Asthma, Allergy, and Airway Center

Durham, North Carolina, United States

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, United States

Optimed Research, LTD.

Columbus, Ohio, United States

Toledo Institute of Clinical REsearch

Toledo, Ohio, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Austin Regional Clinic

Austin, Texas, United States

AARA Research Center

Dallas, Texas, United States

Intermountain Clinical Research

Draper, Utah, United States

Allergy Associates of Utah

Murray, Utah, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Premier Clinical Research

Spokane, Washington, United States

Medical College of Wisconsin, Childrens Hospital

Milwaukee, Wisconsin, United States

University of Alberta Hospital

Edmonton, Alberta, Canada

Yang Medicine

Ottawa, Ontario, Canada

Gordon Sussman Clinical Research, Inc.

Toronto, Ontario, Canada

Clinique Spécialisée en Allergie de la Capitale

Québec, Quebec, Canada

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Hautklinik der Universitätsmedizin Mainz

Mainz, , Germany

HZRM Hamophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, , Germany

University of Milan Luigi Sacco Hospital

Milan, , Italy

Triumpharma Clinical Evaluation Centre

Amman, , Jordan

Adler Medical Plaza

San Juan, , Puerto Rico

Royal London Hospital

London, , United Kingdom

Countries

United States; Canada; Germany; Italy; Jordan; Puerto Rico; United Kingdom

References

Craig T, Tachdjian R, Bernstein JA, Anderson J, Nurse C, Watt M, Yu M, Juethner S. Long-term prevention of hereditary angioedema attacks with lanadelumab in adolescents. Ann Allergy Asthma Immunol. 2024 Dec;133(6):712-719.e1. doi: 10.1016/j.anai.2024.08.001. Epub 2024 Aug 10.

Reference Type: DERIVED

PMID: 39128590 (View on PubMed)

Lumry WR, Maurer M, Weller K, Riedl MA, Watt M, Yu M, Devercelli G, Meunier J, Banerji A; HELP OLE Study Group. Long-term lanadelumab treatment improves health-related quality of life in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2023 Jul;131(1):101-108.e3. doi: 10.1016/j.anai.2023.03.028. Epub 2023 Apr 5.

Reference Type: DERIVED

PMID: 37028510 (View on PubMed)

Craig TJ, Zaragoza-Urdaz RH, Li HH, Yu M, Ren H, Juethner S, Anderson J; HELP and HELP OLE Study Investigators. Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies. Allergy Asthma Clin Immunol. 2022 Sep 24;18(1):85. doi: 10.1186/s13223-022-00721-y.

Reference Type: DERIVED

PMID: 36153561 (View on PubMed)

Banerji A, Bernstein JA, Johnston DT, Lumry WR, Magerl M, Maurer M, Martinez-Saguer I, Zanichelli A, Hao J, Inhaber N, Yu M, Riedl MA; HELP OLE Investigators. Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study. Allergy. 2022 Mar;77(3):979-990. doi: 10.1111/all.15011. Epub 2021 Aug 13.

Reference Type: DERIVED

PMID: 34287942 (View on PubMed)

Riedl MA, Bernstein JA, Craig T, Banerji A, Magerl M, Cicardi M, Longhurst HJ, Shennak MM, Yang WH, Schranz J, Baptista J, Busse PJ. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clin Transl Allergy. 2017 Oct 6;7:36. doi: 10.1186/s13601-017-0172-9. eCollection 2017.

Reference Type: DERIVED

PMID: 29043014 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-005255-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DX-2930-04

Identifier Type: -

Identifier Source: org_study_id