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Efficacy and Safety of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU)

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ClinicalTrials.gov Identifier: NCT03137069
Recruitment Status : Recruiting
First Posted : May 2, 2017
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
The purpose this study is to evaluate the efficacy, safety, and pharmacokinetics of GDC-0853 compared with placebo in participants with Chronic Spontaneous Urticaria (CSU) refractory to anti-histamines.

Condition or disease Intervention/treatment Phase
Urticaria Drug: GDC-0853 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Pilot and Dose-Ranging Study of GDC-0853 in Patients With Refractory Chronic Spontaneous Urticaria (CSU)
Actual Study Start Date : May 26, 2017
Estimated Primary Completion Date : January 23, 2019
Estimated Study Completion Date : January 23, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hives

Arm Intervention/treatment
Experimental: GDC-0853 Cohort 1
Participants will be asked to take GDC-0853 twice daily from Day 1 to 56.
Drug: GDC-0853
High dose of GDC-0853 orally, twice daily, from Day 1 to 56. Participants to have the option to enter an open-label extension (OLE) after completing the 8 week treatment period

Placebo Comparator: Placebo Cohort 1
Participants will be asked to take matching placebo twice daily from Day 1 to 56.
Drug: Placebo
Matching placebo, orally, twice daily, from Day 1 to 56.

Experimental: GDC-0853 Cohort 2
Participants will be asked to take low or middle dose of GDC-0853 once daily or a high dose twice daily from Day 1 to 56.
Drug: GDC-0853
Low dose of GDC-0853 orally, once daily from Day 1 to 56. Participants to have the option to enter an open-label extension (OLE) after completing the 8 week treatment period

Drug: GDC-0853
Middle dose of GDC-0853 orally, once daily from Day 1 to 56. Participants to have the option to enter an open-label extension (OLE) after completing the 8 week treatment period

Placebo Comparator: Placebo Cohort 2
Participants will be asked to take matching placebo either once daily or twice daily from Day 1 to 56.
Drug: Placebo
Matching placebo, orally, once daily, from Day 1 to 56

Experimental: GDC-0853 Cohort 2 (high dose)
Participants will be asked to take GDC-0853 twice daily from Day 1 to 56.
Drug: GDC-0853
High dose of GDC-0853 orally, twice daily, from Day 1 to 56. Participants to have the option to enter an open-label extension (OLE) after completing the 8 week treatment period

Placebo Comparator: Placebo Cohort 2 (high dose)
Participants will be asked to take matching placebo twice daily from Day 1 to 56.
Drug: Placebo
Matching placebo, orally, twice daily, from Day 1 to 56.




Primary Outcome Measures :
  1. Change from Baseline in the Urticaria Activity Score over 7 days (UAS7) at Day 57 [ Time Frame: Baseline and Day 57 ]
    The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals (hives) per 24 hours and the intensity of the pruritus (itch). The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. Because of variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily UASs, ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change score (Day 57 score minus Baseline score) indicates improvement.


Secondary Outcome Measures :
  1. Percentage of Participants who are well Controlled (UAS7 ≤ 6) [ Time Frame: Day 57 ]
    The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals (hives) per 24 hours and the intensity of the pruritus (itch). The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. Because of variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily UASs, ranging from 0 to 42 per week. A higher score indicates worse disease. Participants with UAS7 score ≤6 are considered well controlled.

  2. Change from Baseline in the UAS7 at Day 29 [ Time Frame: Baseline and Day 29 ]
    The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals (hives) per 24 hours and the intensity of the pruritus (itch). The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. Because of variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily UASs, ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change score (Day 29 score minus Baseline score) indicates improvement.

  3. Number of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to 4 weeks after the last dose (Up to Week 12) ]
    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

  4. Area under the Concentration-time Curve from Time 0 to Time t (AUC0-T) [ Time Frame: Pre-dose Day 1, pre-dose Day 8 and on Day 57 ]
    AUC(0-t) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated time (0-t). AUC is a measure of the plasma concentration of GDC-0853 over time.

  5. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose Day 1, pre-dose Day 8 and on Day 57 ]
    Cmax is the maximum observed GDC-0853 plasma concentration.

  6. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pre-dose Day 1, pre-dose Day 8 and on Day 57 ]
    The Tmax is the time from GDC-0853 administration to reach Cmax for GDC-0853.

  7. Steady-State Concentration at the end of a Dosing Interval (Ctrough) [ Time Frame: Pre-dose Day 1, pre-dose Day 8 and on Day 57 ]
    Steady-state concentration of GDC-0853 at the end of a dosing interval will be monitored.

  8. Plasma Terminal Half-Life (t1/2) of GDC-0853 [ Time Frame: Pre-dose Day 1, pre-dose Day 8 and on Day 57 ]
    Plasma terminal half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half.

  9. Apparent Oral Clearance (CL/F) of GDC-0853 [ Time Frame: Pre-dose Day 1, pre-dose Day 8 and on Day 57 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 18−75 years, inclusive
  • Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1 antihistamines at the time of randomization
  • Willing and able to complete an Urticaria Participant Daily eDiary for the duration of the study
  • No evidence of active or latent or inadequately treated infection with tuberculosis (TB)
  • Partcipants with a history of Bacille Calmette-Guérin (BCG) vaccination should be screened using the QuantiFERON-TB-Gold (QFT) test
  • Only for participants currently receiving proton-pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs): Treatment must be at a stable dose during the 2-week screening period prior to randomization and with a plan to remain at a stable dose for the duration of the study
  • For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 4 weeks after the last dose of study drug. Women must refrain from donating eggs during this same period.

Exclusion Criteria:

  • Treatment with omalizumab or other monoclonal antibody therapies used to treat CSU within 4 months prior to screening or primary nonresponse to omalizumab
  • Use of a non-biologic investigational drug or participation in an investigational study with a non-biologic drug within 30 days prior to study drug administration on Day 1 (or within 5 half-lives of the investigational product, whichever is greater)
  • Use of a biologic investigational therapy or participation in an investigational study involving biologic therapy within 90 days or 5 half-lives, whichever is greater, prior to study drug administration on Day 1
  • Previous treatment with GDC-0853 or other Bruton's tyrosine kinase (BTK) inhibitors
  • Participants whose urticaria is solely due to physical urticaria
  • Other diseases with symptoms of urticaria or angioedema, including urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, or leukemia
  • Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, or other skin disease associated with itch such as psoriasis
  • Routine doses of the following medications within 30 days prior to screening: systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide
  • Prior utilization of intravenous (IV) steroids for treatment of laryngeal angioedema
  • Intravenous immunoglobulin G (IV IG) or plasmapheresis within 30 days prior to screening
  • History of anaphylactic shock without clearly identifiable avoidable antigen
  • Hypersensitivity to GDC-0853 or any component of the formulation
  • Major surgery within 8 weeks prior to screening or surgery planned prior to end of study (12 weeks after randomization)
  • Require any prohibited concomitant medications
  • History of live attenuated vaccine within 6 weeks prior to randomization or requirement to receive these vaccinations at any time during study drug treatment
  • Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal (GI) disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participant participation
  • Current treatment with astemizole, terfenadine, and/or ebastine
  • Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03137069


Contacts
Contact: Reference study Id Number: GS39684 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@roche.com

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Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03137069     History of Changes
Other Study ID Numbers: GS39684
2016-004624-35 ( EudraCT Number )
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases