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A multi-center, double-blinded and open-label extension study to evaluate the efficacy and safety of ligelizumab as retreatment, self-administered therapy and monotherapy in Chronic Spontaneous Urticaria patients who completed studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301

PHRR200819-002796

CQGE031C2302E1

2020-CT0540

A multi-center, double-blinded and open-label extension study to evaluate the efficacy and safety of ligelizumab as retreatment, self-administered therapy and monotherapy in Chronic Spontaneous Urticaria patients who completed studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301

This is a Phase IIIb multi-center, double-blinded and open-label extension study to evaluate efficacy and safety of ligelizumab retreatment with H1-AHs background therapy with conditional options for monotherapy and self-administration.

Start Date Duration in Months Target Completion Date Actual Completion Date
2020-09-21 67 2026-04-21 0000-00-00

Ongoing

Institution Classification Region LTO #
Novartis Healthcare Philippines, Inc. Private Business NCR LTO-3000006283930
Institution Region
Novartis Pharma Services AG Switzerland
Name E-Mail Institution and Institution Address
Anna Liza Calingasin anna_liza.calingasin@novartis.com Novartis Healthcare Philippines, Inc. 5th Floor, Ayala North Exchange Tower 1, Ayala Avenue corner Amorsolo Street, Legazpi Village, Makati City 1229
Name E-Mail Institution and Institution Address
Ivy Emily Peneyro-Vergara ivy_emily.peneyro-vergara@novartis.com Novartis Healthcare Philippines, Inc. 5th Floor, Ayala North Exchange Tower 1, Ayala Avenue corner Amorsolo Street, Legazpi Village, Makati City 1229
Name Expertise Affiliation
Celeste C. Tolentino, MD Dermatology Mary Mediatrix Medical Center
Maria Deanna Ramiscal, MD Dermatology St Luke Medical Center - Global City
Michelle Joy De Vera, MD Dermatology The Medical City
Vermen Verallo-Rowell, MD Dermatology VMV Skin Research Centre + Clinics
Project Location Institutional Ethics Review Board
Mary Mediatrix Medical Center Mary Mediatrix Medical Center Research Ethics Review Committee
St Luke Medical Center - Global City N/A
The Medical City The Medical City - Institutional Review Board
VMV Skin Research Centre + Clinics VMV Skin Research Centre + Clinics - Institutional Review Board

Chronic Spontaneous Urticaria

  • The proportion of subjects with well-controlled disease (UAS7 ≤ 6) at Week 12

  • The proportion of subjects with completely controlled disease (UAS7 = 0) at Week 12
  • Absolute change from extension study baseline in the UAS7 and its components (ISS7 and HSS7) at Week 12
  • Cumulative number of weeks that subjects achieve weekly angioedema activity score (AAS7) = 0 between extension study baseline and Week 12
  • Percentage of subjects achieving DLQI = 0-1 at Week 12
  • The proportion of subjects with well-controlled disease (UAS7 ≤ 6), 12 weeks after starting self-administration
  • In each dose group for each duration of treatment:
    • Occurrence of treatment emergent adverse events during the study
    • Occurrence of treatment emergent serious adverse events during the study
    • Vital signs
    • Lab assessments
  • For the duration of treatment:

    • Occurrence of treatment emergent serious adverse events during study Week 12 onwards
    • Vital signs Week 12 onwards
    • Lab assessments Week 12 onwards
    • Occurrence of treatment emergent adverse events
    • Occurrence of treatment emergent serious adverse events
    • Vital signs
    • Lab assessments

Recruiting

  • Argentina
  • Australia
  • Belgium
  • Brazil
  • Bulgaria
  • Canada
  • France
  • Germany
  • Greece
  • Hungary
  • Italy
  • Japan
  • Malaysia
  • Netherlands
  • Poland
  • Singapore
  • Slovakia
  • South Africa
  • South Korea
  • Spain
  • Taiwan
  • Thailand
  • United Kingdom
  • United States
  • Vietnam

Clinical Trial

CQGE031C2302E1

CTA-2020-16-07-20

2020-07-20

0000-00-00

11

Unspecified

Unspecified

2020-09-21

Inclusion Criteria

Subjects eligible for inclusion in this study must meet all of the following criteria:

  1. Written informed consent must be obtained before any assessment is performed.
  2. 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.
  3. 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.
  4. 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.
  5. 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).
  6. Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedule.
  7. Subjects must not have had any 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. Rescreening may be considered only once.

Exclusion Criteria

Subjects meeting any of the following criteria are not eligible for inclusion in this study.

  1. 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.
  2. Use of omalizumab within 16 weeks of Screening Visit 1
  3. 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).
  4. 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.
  1. 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).
  2. 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 (see Section 8.4.3 of respective preceding study’s protocol). 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.
  1. Any other skin disease associated with chronic itching that might confound the study evaluations and results (e.g. atopic dermatitis, contact dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus etc.).
  2. Any H2-antihistamine use after Visit 1 in this study.
  3. Any LTRA (e.g. montelukast or zafirlukast) use after Visit 1 in this study.
  4. 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.
  1. Prior exposure to any anti-IgE antibody therapy other than omalizumab and ligelizumab.
  2. History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to enrollment.
  3. Inability to comply with study and follow-up procedures.
  4. Subjects taking medications prohibited by the protocol (see Section 6.2.2, Table 6-2).
  5. 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.
  6. Documented history of anaphylaxis.
  7. 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 non-invasive malignant colon polyps that have been removed).
  8. 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.
  9. 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.
  10. 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)/GGT (gamma-glutamyl transferase)/albumin/TBL (total bilirubin )/ALP (alkaline phosphatase) levels of more than 1.5x upper limit of normal (ULN) at Visit 1 or Visit 2.
  11. History of renal disease or creatinine level above 1.5 x ULN at Visit 1 or Visit 2.
  12. Platelets < 100,000/μL at Visit 1 or Visit 2.
  13. 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.
  14. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic (acceptable effective) methods of contraception during dosing of investigational drug (and approx. 4 months, i.e. 5 half-lives, after last dose of ligelizumab). Basic (acceptable effective) methods of contraception 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 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 and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or 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.

Interventional

QGE031

Investigational (Name and strength)

Pharmaceutical Dosage Form

Route of Administration

Supply Type

Ligelizumab 120 mg per 1 mL

Liquid in vial

s.c.

Open-label subject kits; vials

Ligelizumab (QGE031) 120 mg per 1 mL

Solution for injection in a pre-filled syringe

s.c

Open-label subject kits; pre-filled syringe

Date Amendment Classification Reason
2021-07-23 Amendments related to the protocol Exclusion criteria
2021-07-23 Amendments related to the protocol Number of participants
2021-07-23 Amendments related to the protocol Inclusion criteria
2021-07-23 Amendments related to the protocol Informed consent

Randomized

Double Blind

Subjects, investigator staff and personnel performing the study assessments for studies CQGE031C2302 and CQGE031C2303 will remain blinded to the identity of the treatment from the time of enrollment (Visit 201, Week 0) until all subjects in this study have completed Week 12 in the first half of the treatment period. An unblinded study monitor will visit the study site to monitor study drug related administration (see Section 11.3). No blinding is required for subjects transitioning from study CQGE031C2202 and CQGE031C1301, as all subjects will receive 120 mg s.c. q4w ligelizumab. Treatment blinding will be maintained at Visits 201, 202 and 203 (Weeks 0, 4 and 8) when subjects are being administered with liquid in vial (see Section 3.3) using the following methods: Treatment assignment data are kept strictly confidential until the time of unblinding, and will not be accessible by anyone else involved in the study with the following exceptions: Bioanalyst (PK): to enable identification of samples from the ligelizumab treatment arms of the study to facilitate bioanalysis; Independent personnel (external to Novartis) involved in monitoring anaphylaxis, neoplastic and cerebro-cardiovascular events (Adjudication Committee members), if needed; and An independent DMC (see Section 10.2.3) and the independent statistician supporting the DMC activities (Table 6-4). The following measures will be applied to keep the subject and study personnel blinded despite differences of the investigational treatments in volume: The investigational drug must be prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded administrator who are both not involved in any of the study assessments. If an unblinded pharmacist is not available, preparation and administration of the investigational drug may also be performed by a single independent unblinded site person if he/she is authorized to do both. Preparation of the investigational drug must be done in a separate space/room where subjects and blinded study personnel have no access during time of preparation. To blind the liquid volume in the syringe, the syringe must be covered by a strip of opaque tape. The differences in length of the syringe plunger, related to the differences in the volume, should also be covered by the way of administration (see Pharmacist Manual). The prepared syringes must be placed on a tray which is covered by an opaque towel to ensure the syringes are not visible to the subject at any time. The independent unblinded authorized site persons (pharmacist/administrator) should not communicate the volume and any perceived sensation associated with the administration of the investigational drug. The subject will be instructed to look away, from the tray of prepared syringes (whenever the tray is uncovered) and from the injection site.

Single

The purpose of this extension study (up to 104 weeks of treatment and up to 52 weeks of post-treatment follow-up) is to establish efficacy and safety of ligelizumab (QGE031) 120 mg s.c. q4w. This will be assessed in adult and adolescent CSU patients who have completed one of the studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301 (the "preceding studies") and who have relapsed, following treatment in these preceding studies, despite standard of care treatment with H1-antihistamines (H1-AH) (at local label approved doses), in the following scenarios:

  • re-treatment with ligelizumab 72 or 120 mg s.c. q4w following treatment in the preceding studies;
  • self-administration of ligelizumab 120 mg s.c. q4w outside of the clinic setting;
  • ligelizumab 120 mg s.c. q4w used as monotherapy, i.e. when background H1-AH medication is discontinued

In addition, this study will evaluate whether ongoing long-term treatment drives drug-mediated remission of disease. This study will also fulfill the Novartis commitment to provide post-trial access to patients who have completed studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301.

Phase III

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