Lanadelumab in patients with Hereditary angioedema MedDRA version: 20.0 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10074782 Term: Hereditary angioedema breakthrough attack System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Takzhyro (Lanadelumab)
Product Name: Lanadelumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
Sponsors
Charité - Universitätsmedizin Berlin Klinik für Dermatologie und Allergologie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults (18 years or older) • Documented HAE-nC1 (adapted from the definition by Zuraw et al., Allergy Asthma Proc 2012): - A history of recurrent angioedema in the absence of concomitant hives or concomitant use of a medication known to cause angioedema. - Documented normal or near normal C4, C1-INH antigen, and C1-INH function. - One of the following: A) Demonstration of a FXII / PLG / ANGPT1 mutation that is associated with the disease. B) A positive family history of angioedema and documented evidence of lack of efficacy of chronic high dose antihistamine therapy (cetirizine at 40 mg/day or the equivalent, for at least 1 month and an interval expected to be associated with three or more attacks of angioedema). • Clinical symptoms of angioedema attacks (at least 2 attacks within the last 3 months prior to screening; and at least 2 attacks within 12 weeks at maximum in the run-in period). • Able to read, understand and willing to sign the informed consent form and abide with study procedures. • No participation in other clinical trials 4 weeks before and after participation in this study. Males and females who are fertile and sexually active must adhere to contraception requirements for the duration of the study: • Females of childbearing potential must agree to be abstinent or else use any two of the following medically acceptable forms of contraception from the screening period through 30 days after the final study visit: progestin-only oral contraceptive, condom with or without spermicidal jelly, diaphragm or cervical cap with spermicidal jelly, or intra-uterine device (IUD, all types). A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception. • 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 last IMP injection. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Any other forms of angioedema not related to HAE-nC1. • Treatment with a live (attenuated) virus vaccine within 4 weeks prior to Baseline visit. • Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening. • Use of long-term prophylactic therapy for HAE (C1-INH, attenuated androgens, or antifibrinolytics) within 2 weeks prior to the start of the treatment period (Day 0). • Use of short-term prophylaxis for HAE by non-rollover subjects within 7 days prior to the start of the treatment period (Day 0). 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 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. • 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). • Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial. • Enrollment in another investigational treatment or device study or use of an investigational agent, or less than 4 weeks or 5 half-lives, whichever is longer, since end of another investigational device or drug trial. • Subjects for whom there is concern about compliance with the protocol procedures. • Patients with known hypersensitivity to any constituent of the products of lanadelumab. • Dementia, altered mental status, or any psychiatric condition, or stay in an institution further to an official or court order that would prohibit the understanding or rendering of informed consent or participation in the study. • Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of Lanadelumab on the clinical signs and symptoms in patients with HAE-nC1.;Secondary Objective: To assess the effect of Lanadelumab on the patients’ quality of life, disease control, and disease activity as well as the safety and tolerability following administration.;Primary end point(s): The primary endpoint is the change of Angioedema Activity Score (AAS) at week 48 compared to the AAS at week 0 (baseline). ;Timepoint(s) of evaluation of this end point: Week o (baseline) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety of patients treated with Lanadelumab: This includes physical examination, routine safety laboratory assessments, vital signs, and adverse event reporting. 2. Change in disease activity as assessed by AAS, AECT and/or AE-Qol (from Baseline to visit 7, and from visit 7 to visit 8). 3. Change in number of symptom-free days per week (AAS) (from Baseline to visit 7, and from visit 7 to visit 8). 4. Change in quality-of-life scores assessed by AE-Qol (from Baseline to visit 7, and from visit 7 to visit 8). 5. Change in number of intake of rescue medication (from Baseline to visit 7, and from visit 7 to visit 8). 6. Change in physician and patient global assessment (from Baseline to visit 7, and from visit 7 to visit 8). 7. Serum levels at baseline (Day 1) and changes from Baseline to Visits 3, 5, 7 and 8 of serum levels of potential biomarkers in Lanadelumab-treated patients (e.g. FXII, prekallikrein and cHMWK levels). 8. Rates of Lanadelumab-treated patients with relapse, rebound, sustained treatment effects at visit 8. ;Timepoint(s) of evaluation of this end point: see above | — |
Countries
Germany
Contacts
Public ContactMarcus Mauer
Charité - Universitätsmedizin Berlin; Dpt. of Dermatology and Allergy
Outcome results
None listed