E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
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E.1.1.1 | Medical condition in easily understood language |
Systemic lupus erythematosus (SLE) is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the clinical efficacy of GDC-0853 in combination with standard of care (SOC) |
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E.2.2 | Secondary objectives of the trial |
•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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 </= 40 mg/day prednisone (or equivalent)
Stable doses of anti-malarial or immunosuppressive therapies |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. SRI-4 response at Week 48 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Bulgaria |
Chile |
Colombia |
Germany |
Korea, Republic of |
Mexico |
Portugal |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as the last patient, last safety follow-up visit in this protocol, last patient to discontinue from the study, or the last patient enrolled into an OLE, whichever occurs latest. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |