Study of Efficacy and Safety of Ligelizumab in Chronic Spontaneous Urticaria Patients Who Completed a Previous Study With Ligelizumab

Overview

About this study

The purpose of this study is to establish effectiveness and safety of ligelizumab. This will be assessed in patients with chronic spontaneous urticaria (CSU) who have completed a preceding ligelizumab study and have relapsed, following treatment in these preceding studies, despite standard of care H1-antihistamine (H1-AH) treatment. For this curreent study only adults will be enrolled, as no adolescents were enrolled in the previous study (CQGE031C2303).  In a subset of subjects, the safety and efficacy of ligelizumab monotherapy will be assessed.  This study will also fulfill the Novartis commitment to provide post-trial access to patients who have completed studies CQGE031C2302, CGQE031C2303, CQGE031C2202 or CQGE031C1301.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed.
  • Subject’s, parent’s or legal guardian’s signed written informed consent and child’s assent, if appropriate, must be obtained before any assessment is performed. Of note, if the subject reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study Informed Consent Form (ICF) at the next study visit.
  • Subjects who successfully completed all of the treatment period and the follow-up period of any of the following studies: CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301.
    • Subjects who had completed the preceding studies prior to start of this extension study are also allowed to participate, provided they perform the full Screening Period as soon as the extension study had been initiated at their study site.
  • Male and female, adult and adolescent subjects ≥12 years of age (NOTE: Recruitment of adolescent subjects, ≥ 12 to < 18 years of age, will be in accordance with local regulatory/ethics committee requirements).
  • Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedule.
  • Subjects must not have had missing eDiary entries in the 7 days prior to the first visit of the first half of the treatment period* or first visit of the first observation period (at least 12 out of 14 records for HSS and ISS respectively must be present in the week the UAS7 score is assessed). *Subjects must reach UAS7 score ≥ 16 prior to treatment. For subjects entering treatment directly from the screening period the score will be assessed in the 7 days prior to first treatment visit. Rescreening may be considered only once.

Exclusion Criteria:

  • Use of investigational drugs, other than those in use in the preceding studies, at the time of enrollment, or within 30 days or 5 half-lives prior to Visit 1 (Screening visit), whichever is longer.
  • Use of omalizumab within 16 weeks of Visit 101 or 201 (whichever occurs first).
  • History of hypersensitivity to the study drug ligelizumab or its components, or to drugs of similar chemical classes (i.e., to murine, chimeric, or human antibodies).
  • New onset or signs and symptoms of any form of chronic urticarias other than CSU during the preceding studies CQGE031C2302, CQGE031C2303 or CQGE031C2202.
  • This includes, but is not limited, to the following:
    • Inducible urticaria: symptomatic dermographism (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria. 5. Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency).
  • Subjects with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic helminth according to local guidelines. All subjects should have been assessed for evidence of parasitic infection at Visit 1999 of the preceding studies. If stool testing is positive for pathogenic helminthic organisms, the subject will not be enrolled in to this extension study and will not be allowed to rescreen.
  • In the event that stool samples from Visit 1999 of the preceding studies were not collected or the results from these are not available, subjects will be assessed for evidence of parasitic infection at Visit 1.  If stool testing is positive for pathogenic helminthic organisms, the subject will not be enrolled to this extension study and will not be allowed to rescreen.
  • Any other skin disease associated with chronic itching that might in the opinion of the investigator, confound the study evaluations and results (e.g., atopic dermatitis, contact dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus etc.).
  • Any H2-antihistamine use after Visit 1 in this study.
  • Any LTRA (e.g., montelukast or zafirlukast) use after Visit 1 in this study.
  • Any H1-antihistamine background medication used at greater than the local label approved doses after Visit 1.
  • H1-antihistamine rescue medication may be used at up to 4 times the local label approved doses after Visit 1, at the discretion of the investigator.
  • Prior exposure to any anti-IgE antibody therapy other than omalizumab and ligelizumab.
  • History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to enrollment.
  • Inability to comply with study and follow-up procedures.
  • Subjects taking medications prohibited by the protocol.
  • Contraindications to or hypersensitivity to study drugs including but not limited to fexofenadine, loratadine, desloratadine, cetirizine, levocetirizine, rupatadine or epinephrine or any of their ingredients.
  • Documented history of anaphylaxis.
  • Onset of malignancy of any organ system within the past 5 year (except for basal cell carcinoma or actinic keratoses or Bowen disease (carcinoma in situ) that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or noninvasive malignant colon polyps that have been removed).
  •  
  • Presence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association Class III/IV left ventricular failure, arrhythmia, uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, metabolic or other pathological conditions (such as but not limited to cerebrovascular disease, neurodegenerative diseases or other neurological disease, uncontrolled hypo- and hyperthyroidism and other autoimmune diseases, hypokalemia, hyperadrenergic state, or ophthalmologic disorder) that could interfere with or compromise the safety of the subject, interfere with evaluation or interpretation of the study results or preclude completion of the study.
  • Medical examination or laboratory findings that suggest the possibility of decompensation of co-existing conditions for the duration of the study. Any items that are cause for uncertainty will be reviewed with the investigator.
  • History of, or current treatment for, hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or AST (aspartate aminotransferase)/ALT (alanine aminotransferase)/albumin/TBL (total bilirubin ) levels of more than 1.5x upper limit of normal (ULN) at Visit 1 or Visit 2*.
  • History of renal disease or creatinine level above 1.5 x ULN at Visit 1 or Visit 2*.
  • Platelets < 100,000/μL at Visit 1 or Visit 2*.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
  • Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of investigational drug (and approx. 4 months; i.e., 5 half-lives, after last dose of ligelizumab). Effective contraception methods include:
    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable effective methods of contraception;
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
    • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject;
    • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/vaginal suppository;
    • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device or intrauterine system In case of use of oral contraception, women should have been stable on the same contraceptive pill for a minimum of 3 months before taking investigational drug. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). Women are considered not of child bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the informed consent form (ICF).
    • *Subjects who did not meet applicable eligibility criteria at Visit 2, as listed above, will be discontinued from the study and will not enter treatment. Since these subjects have been initially eligible at Visit 1 and participated in the first observation period, they will not be considered screen failure subjects if they do not enter treatment.

Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Gerald Volcheck, M.D.

Closed for enrollment

Contact information:

Kay Bachman R.N., C.C.R.C.

(507) 284-5689

bachman.kay@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

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CLS-20489835

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