Lanadelumab in patients with Factor XII-associated cold autoinflammatory syndrome (FACAS) MedDRA version: 20.0 Level: PT Classification code 10072220 Term: Autoinflammatory disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Takhzyro® 300 mg Injektionslösung
Product Name: Lanadelumab
Product Code: na
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
Sponsors
Charité – Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adolescents (12 - 17 years old) and adults (18 years or older) • Documented FXII-associated autoinflammatory disorder (FACAS) by positive genetic analysis result • Clinical symptoms of cold-associated wheals, arthralgia, headache, fatigue • Able to read, understand and willing to sign the informed consent form and abide with study procedures 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 else use one of the following medically acceptable forms of contraception from the screening period through 30 days after the final study visit: progestin-only oral contraceptive, intrauterine device, progestin depot injection or progestin implant. A female whose male partner has had a vasectomy must agree to use one additional form of highly effective contraception (Pearl-Index =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: • Any other forms of urticaria or angioedema not related to genetic mutations within the FXII gene • Concurrent/ongoing treatment with biologics or recent treatment (less than 5 half-lives) • With anakinra within 7 days prior to screening, with canakinumab within 100 days prior to screening • with oral/parental corticosteriods greater than 10 mg/d within 2 weeks prior to screening o other immunosuppressives within 4 weeks or 5 half-lives prior to screening, whichever is longer • 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 prophylactic therapy with C1-INH, attenuated androgens, or antifibrinolytics within 2 weeks prior to the start of the treatment period (Day 0) • Any of the following liver function test abnormalities: o alanine aminotransferase (ALT) > 3x upper limit of normal, or o aspartate aminotransferase (AST) > 3x upper limit of normal, or o 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 immuno-compromised 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 • 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 of FXII-associated cold autoinflammatory syndrome (reduction in symptomatic days with urticarial rash, arthralgia, headache, chills);Secondary Objective: • To assess the effect of Lanadelumab on inflammation markers (CRP, ESR, SAA, S100A8/9) • To assess the effect of Lanadelumab on the patients' quality of life • To assess the safety and tolerability following administration of Lanadelumab • To assess the effect of Lanadelumab on the kallikrein-kinin pathway and cytokine release (prekallikrein levels, cHMWK levels, IL-1ß release);Primary end point(s): The primary endpoint of the study is the change in patient-reported disease activity total score (mean of weeks 9 to 12 compared to mean of weeks -4 to -1 (baseline)). Patient-reported disease activity is assessed by a daily health assessment form (FACAS-DHAF) evaluating the severity of 5 key symptoms of FACAS: urticarial rash, fatigue, chills/fever, arthralgia and headache. Patients are asked to grade the severity of each symptom daily on a numeric rating scale (NRS) ranging from 0 (very good) to 10 (very bad). The daily total score is defined as the mean of the 5 individual symptom scores. The total score at baseline is defined as the mean of daily total scores from week -4 to -1. The total score at weeks 9 to 12 is defined as the mean of daily total scores from week 9 to 12. The primary endpoint is the difference of these two scores (total score at weeks 9 to 12 minus total score at baseline). The mean score over 4 weeks will be calculated if at least 70% of the daily patient-reported assessments are available (e.g. if at least 20 out of 28 diary values are available). Otherwise, the mean score over 4 weeks will be regarded as missing. ;Timepoint(s) of evaluation of this end point: weeks 9 to 12 compared to weeks -4 to -1 (baseline) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in PR-DA urticarial rash score at weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline). • Change in PR-DA fatigue score at weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline). • Change in PR-DA chills/ fever score at weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline). • Change in PR-DA arthralgia score at weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline). • Change in PR-DA headache score at weeks 9 to 12 and weeks 24 to 28, each compared to weeks -4 to -1 (baseline). • Change in PR-DA total score at weeks 24 to 28 compared to weeks -4 to -1 (baseline). • Change in inflammation markers CRP, ESR, SAA, S100 A8/9 (from Baseline to week 12 and week 28). • Change in disease-specific quality-of-life assessed by Dermatology Life Quality Index (DLQI) over the study (from Baseline to week 12 and week 28). • Changes in generic quality-of-life assessed by 36-Item Short Form Health Survey (SF-36) (from Baseline to week 12 and week 28). • Safety: physical examination, routine safety laboratory assessments, vital signs, and adverse events. • Change in physician global assessment as assessed by verbal rating scale from 0-10 (0=no symptoms; 10=very severe symptoms) over the study (from Baseline to week 12 and week 28). • Changes from Baseline to week 28 of plasma levels of potential biomarkers in Lanadelumab-treated patients (e.g. FXII, prekallikrein and cHMWK levels, IL-1ß release from donor PBMCs).;Timepoint(s) of evaluation of this end point: from Baseline to week 12 and week 28 | — |
Countries
Germany
Contacts
Public ContactProf. Marcus Maurer
Institute of Allergology
Outcome results
None listed