A Study of the Safety and Efficacy of GDC 0853 in Patients With Moderate to Severe Active Systemic Lupus Erythematosus

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2016-001039-11-GB
• Date of registration: 24/08/2016
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: A Study of the Safety and Efficacy of GDC 0853 in Patients With Moderate to Severe Active Systemic Lupus Erythematosus
• Scientific title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFICACY OF GDC-0853 IN PATIENTS WITH MODERATE TO SEVERE ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS
• Date of first enrolment: 16/11/2016
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001039-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Bulgaria, Chile, Colombia, Germany, Korea, Republic of, Mexico, Portugal, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Age 18-75 years, inclusive
- American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) criteria at any time prior to or at screening
- At least one serologic marker of SLE at screening as follows: positive antinuclear antibody (ANA) test by immunofluorescent assay with titer >= 1:80; or positive anti-double-stranded DNA (anti-dsDNA) antibodies; or positive anti-smith antibody
- At both screening and Day 1, moderate to severe active SLE, defined as meeting all of the following unless indicated otherwise: SLE Disease Activity Index (SLEDAI) -2K score >=8 (at screening only) with clinical SLEDAI-2K score >= 4.0 (at both screening and Day 1); Physician’s global assessment >= 1.0 (out of 3); and currently receiving at least one standard oral treatment (e.g., corticosteroids, anti-malarials, and/or immunosuppressants) for SLE within specified dose ranges
- Participants must be willing to avoid pregnancy
- If on oral corticosteroids (OCS), the dose must be Stable doses of anti-malarial or immunosuppressive therapies
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
- Neuropsychiatric or central nervous system lupus manifestations
- History of receiving a solid organ transplant
- Newly diagnosed (within the last 24 weeks) transverse myelitis
- Evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB)
- History of cancer, including hematological malignancy and solid tumors, within 10 years of screening
- Need for systemic anticoagulation with warfarin, other oral or injectable anticoagulants, or anti-platelet agents
- Evidence of chronic and/or active hepatitis B or C


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus
MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: GDC-0853
Product Code: RO7010939/F13
Pharmaceutical Form: Tablet
INN or Proposed INN: not available yet
CAS Number: 1434048-34-6
Current Sponsor code: GDC-0853, RO7010939
Other descriptive name: GDC-0853 RO7010939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1. SRI-4 response at Week 48

Timepoint(s) of evaluation of this end point: 1. Week 48

Secondary Objective: •To evaluate the clinical efficacy of GDC-0853 over time using the Systemic Lupus Erythematosus Responder Index (SRI-4) as a standardized disease activity measure
•To evaluate the clinical efficacy of GDC 0853 over time using BICLA and SRI-6 as standardized disease activity measures
•To evaluate if patients with high plasmablast signature levels have an enhanced clinical response to GDC-0853 relative to patients with low levels
•To evaluate the safety of GDC-0853 in combination with SOC therapy in patients with moderate to severe active SLE
•To characterize the pharmacokinetics (PK) of GDC-0853 in patients using a population PK approach

Main Objective: To evaluate the clinical efficacy of GDC-0853 in combination with standard of care (SOC)

Secondary Outcome(s)

Secondary end point(s): 1. SRI-4 response at Week 48 with a sustained reduction of OCS dose to < 10 mg/day and <= Day 1 dose during Week 36 through Week 48
2. SRI-4 response at Week 24 with a sustained reduction of OCS dose to < 10 mg/day and <= Day 1 dose during Week 12 through Week 24
3. SRI-4 response at Week 24
4. SRI-4 response at Week 48 in patients with high vs. low plasmablast signature levels
5. SRI-4 response with a sustained reduction of OCS dose to = 10 mg/day and = Day 1 dose during Week 36 through 48 in patients with high vs. low plasmablast signature levels
6. SRI-6 response at Weeks 24 and 48
7. BICLA response at Weeks 24 and 48
8. Incidence of adverse events using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale to grade adverse events
9. Changes in vital signs, physical findings, electrocardiogram (ECGs), and clinical laboratory results following GDC-0853 administration
10. Plasma concentrations of GDC-0853 at specified timepoints

Timepoint(s) of evaluation of this end point: 1. Week 48
2-3. Week 24
4-5. Week 48
6-7. Week 24 and Week 48
8-9. Up to 60 weeks
10. Pre dose at Week 1, Week 4, Week 24, and Week 48; at unscheduled or flare or early termination visit

Secondary ID(s)

GA30044

Source(s) of Monetary Support

Genentech Inc. c/o F. Hoffman-La Roche Ltd.

Ethics review

Status: Approved
Approval date:
Contact: