Long-term efficacy and safety study to evaluate DX-2930 in preventing angioedema attacks in patients with Type I and Type II hereditary angioedema (HAE)

• Register: EUCTR
• Last refreshed on: 29 April 2020
• Main ID: EUCTR2015-005255-27-DE
• Date of registration: 24/05/2016
• Prospective Registration: Yes
• Primary sponsor: Dyax Corp., (an indirect, wholly-owned subsidiary of Shire plc.)
• Public title: Long-term efficacy and safety study to evaluate DX-2930 in preventing angioedema attacks in patients with Type I and Type II hereditary angioedema (HAE)
• Scientific 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)
• Date of first enrolment: 14/11/2016
• Target sample size: 225
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005255-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Germany, Italy, Jordan, United Kingdom, United States

Contacts

• Name: Clinical Trials Operations
• Affiliation: Voisin Consulting

• Name: Clinical Trials Operations
• Affiliation: Voisin Consulting

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female HAE subjects who are 12 years of age or older at the time of screening.
2. Documented diagnosis of HAE (Type I or II) based on 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 (or a prior DX-2930 study) that confirm HAE Type I or II: C1 inhibitor (C1-INH) functional level < 40% of the normal level. Subjects 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. Subjects may be retested if results are incongruent with clinical history or believed by the investigator to be confounded by recent 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).
• 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.
3. A historical baseline HAE attack rate of at least 1 attack per 12 weeks 4. Adult subjects and caregivers of subjects under the age of 18 are willing and able to read, understand, and sign an informed consent form. Subjects age 12 to 17, whose caregiver has provided informed consent, are willing and able to read, understand and sign an assent form.
5. Males and females who are fertile and sexually active must adhere to contraception requirements for the duration of the study as follows:
• Females of childbearing potential must agree to be abstinent or it is recommended to use highly effective forms of contraception from screening 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.
• 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.
• 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 21
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion criteria:
1. Discontinued from DX-2930-03 after enrollment for any reason.
2. If rolling over from DX-2930-03, presence of important safety concerns that would preclude participation in this study.
3. Concomitant diagnosis of another form of chronic, recurrent angioedema such as acquired angioedema (AAE), HAE with normal C1-INH (also known as HAE Type III), idiopathic angioedema, or recurrent angioedema associated with urticaria.
4. 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.
5. Exposure to angiotensin-converting enzyme (ACE) inhibitors within 4 weeks prior to study 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.
6. Unwilling to discontinue use of long-term prophylactic therapy for HAE (C1-INH, attenuated androgens, or antifibrinolytics) within 3 weeks after starting DX-2930 treatment.
7. 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).
8. Pregnancy or breastfeeding.
9. Subject 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 (e.g., 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).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type I and Type II Hareditary Angioedema (HAE)
MedDRA version: 20.0 Level: LLT Classification code 10075280 Term: Hereditary angioedema attack System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: DX-2930
Product Code: DX-2930
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Lanadelumab
CAS Number: 1426055-14-2
Current Sponsor code: DX-2930
Other descriptive name: DX2930
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): To evaluate the long-term safety of repeated subcutaneous administrations of DX-2930.
Safety Measures:
• AEs including SAEs and AESI
• Clinical Laboratory testing (hematology, clinical chemistry, coagulation and urinalysis)
• Vitals signs including blood pressure, heart rate, body temperature and respiratory rate
• Physical Examination
• 12-lead ECG

Main Objective: To evaluate the long-term safety of repeated subcutaneous (SC) administrations of DX-2930

Secondary Objective: To evaluate the long term efficacy of DX-2930 in preventing HAE attacks
To characterize the outer bounds of dosing frequency for DX-2930

Timepoint(s) of evaluation of this end point: 30 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 30 months

Secondary end point(s): Efficacy Endpoints:
• Time to first HAE attack for rollover subjects (based upon time from first open label study dose until first HAE attack)
• Number of investigator confirmed HAE attacks during the treatment period
• Number of investigator confirmed HAE attacks requiring acute treatment during the treatment period
• Number of moderate or severe HAE attacks during the treatment period
• Number of high-morbidity HAE attacks during the treatment period; a high-morbidity HAE attack is defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation < 24 hours), hemodynamically significant (systolic blood pressure < 90, requires IV hydration, or associated with syncope or near-syncope) or laryngeal.

Secondary ID(s)

DX-2930-04

116647

2015-005255-27-GB

Source(s) of Monetary Support

Dyax Corp.

Ethics review

Status: Approved
Approval date: 14/11/2016
Contact: