Clinical trial NCT02741596: Long-term Safety and Efficacy Study of DX-2930 (SHP643) to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE
Official title: HELP Study ExtensionTM: An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of DX-2930 for Prevention Against Acute Attacks of Hereditary Angioedema (HAE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Keywords: DX-2930(SHP643)
Dyax
Hereditary Angioedema
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-04-18
Enrollment: 212
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


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).

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of the study up to follow-up (Day 952)
Secondary outcomes:
measure: Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During the Treatment Period
timeFrame: Up to Day 924
measure: Rate of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During the Treatment Period
timeFrame: Up to Day 924
measure: Rate of Moderate or Severe Hereditary Angioedema (HAE) Attacks During the Treatment Period
timeFrame: Up to Day 924
measure: Rate of High-Morbidity Hereditary Angioedema (HAE) Attacks During the Treatment Period
timeFrame: Up to Day 924
measure: Time to First Investigator-Confirmed Hereditary Angioedema (HAE) Attacks in Rollover Participants
timeFrame: Up to Day 924
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Medical Research of Arizona
state: Arizona
city: San Diego
country: United States
facility: University of California San Diego
state: California
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: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Chevy Chase
country: United States
facility: Institute Asthma and Allergy
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Plymouth
country: United States
facility: Midwest Immunology Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Belleville
country: United States
facility: Hudson-Essex Allergy, LLC
state: New Jersey
city: Ocean City
country: United States
facility: Atlantic Research Center, LLC
state: New Jersey
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
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: Durham
country: United States
facility: Duke Asthma, Allergy, and Airway Center
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD.
state: Ohio
city: Toledo
country: United States
facility: Toledo Institute of Clinical REsearch
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Draper
country: United States
facility: Intermountain Clinical Research
state: Utah
city: Murray
country: United States
facility: Allergy Associates of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Childrens Hospital
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Ottawa
country: Canada
facility: Yang Medicine
state: Ontario
city: Toronto
country: Canada
facility: Gordon Sussman Clinical Research, Inc.
state: Ontario
city: Quebec City
country: Canada
facility: Clinique Spécialisée en Allergie de la Capitale
state: Quebec
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Mainz
country: Germany
facility: Hautklinik der Universitätsmedizin Mainz
city: Mörfelden-Walldorf
country: Germany
facility: HZRM Hamophilie Zentrum Rhein Main GmbH
city: Milan
country: Italy
facility: University of Milan Luigi Sacco Hospital
city: Amman
country: Jordan
facility: Triumpharma Clinical Evaluation Centre
city: San Juan
country: Puerto Rico
facility: Adler Medical Plaza
city: London
country: United Kingdom
facility: Royal London Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.