| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active Sjogren’s Syndrome |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| 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 | 10040767 |
| E.1.2 | Term | Sjogren's syndrome |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| 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 assess the efficacy of filgotinib, GS-9876, and GS-4059 in adult subjects with active Sjogren's syndrome |
|
| E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of filgotinib, GS-9876, and GS-4059 in adult subjects with active Sjogren's syndrome
To assess the effect of filgotinib, GS-9876, and GS-4059 on patient reported outcomes in active Sjogren's syndrome, including fatigue, disability, and quality of life |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Phamacokinetic substudy: PK Substudy Analysis Set, which includes all subjects in the Safety Analysis Set who have enrolled into the PK substudy, and have intensive PK concentration data to provide interpretable results for the specific parameters of interest for the analyte under evaluation. Optional pharmacogenomic substudy - Subjects who provide their additional, separate, specific written consent will provide a single blood sample for genetic assessment. This sample may be collected any time during the study, starting at the Day 1 visit. |
|
| E.3 | Principal inclusion criteria |
1) Male or female 18 to 75 years of age (inclusive) at the time of signing initial consent, with all of the following at Screening: a. Diagnosis of SjS based on AECG classification, b. Active SjS, with ESSDAI ≥5 c. Seropositivity for anti-SSA or anti-SSB, per central laboratory as described in the protocol
2) A negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 are required for female subjects of child-bearing potential
3) Starting at the time of written consent, through the study, and for 90 days (male) and 36 days (female) following their last dose of study drug: a. Male and female subjects of childbearing potential who engage in heterosexual
intercourse must agree to use protocol specified method(s) of contraception, b. Male subjects must agree to refrain from sperm donation c. Female subjects must agree not to breastfeed or to donate/harvest eggs for the purpose of fertilization,
4) Subjects with prior exposure to a B-cell depleting bDMARD (at any time) must have a documented return of CD19+ B cells at Screening.
5) Stable dose (defined as no change in prescription for at least 4 weeks prior to Day 1) of NSAIDs, HCQ, MTX and/or oral corticosteroids is permitted during the study, but not required (see protocol for definitions, full list of allowed prior and concomitant medications and permitted doses).
6) Meet tuberculosis (TB) Screening criteria as defined in the protocol
7) Are willing and able to sign the informed consent form and comply with study requirements, procedures, and scheduled visits. |
|
| E.4 | Principal exclusion criteria |
1) Concurrent treatment at Screening with any bDMARD
2) Any prior use of cyclophosphamide
3) Use of cyclosporine within 4 weeks prior to the first dose of study drug (Day 1) or anticipated chronic use while on study
4) Clinically significant abnormalities on 12-lead ECG as judged by the investigator.
5) Treatment with moderate or strong CYP3A inducers or inhibitors within 2 weeks, or strong P-gp inducers within 3 weeks prior to the first dose of study drug or anticipated chronic use while on study
6) Participation in any clinical study of an investigational drug within 4 weeks or 5 drug half-lives prior to Screening, whichever is longer. Washout duration for exposure to investigational biologics should be discussed with the sponsor
7) Treatment with any commercially available or investigational drug listed as listed in the protocol within 3 months of Screening
8) History of opportunistic infection or immunodeficiency syndrome which would put the subject at risk, as per investigator judgment
9) History of symptomatic herpes zoster or herpes simplex infection within 12 weeks prior to Screening or history of disseminated/complicated herpes zoster infection (multi-dermatomal involvement, ophthalmic zoster, CNS involvement or postherpetic neuralgia) at any time
10) Known hypersensitivity to the study drug, its metabolites, or any of the excipients, or previous clinically significant allergic reaction to any drug, per judgment of the investigator
11) Another highly active inflammatory/autoimmune/rheumatic disease (such as highly active RA, highly active SLE, highly active nephritis or CNS inflammation) which would compromise subject safety or interfere with the conduct of the study.
12) History of head/neck irradiation, sarcoidosis, graft v host disease, or IgG4 related disease
13) Female subjects who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study up to 36 days after the last dose of study drug or males who are planning to father a child during the study up to 90 days after the last dose of study drug
14) Major surgery (requiring regional block or general anesthesia) within 30 days prior to Screening, or planned during the study
15) History of live or attenuated vaccines within 30 days of Day 1, or planned during the study period or for 12 weeks after the subject's last dose of study drug.
16) History of malignancy within the past 5 years prior to Screening (except for adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ, with no evidence of recurrence).
17) Positive serology for human immunodeficiency virus (HIV) 1 or 2 at Screening,
18) Hepatitis B virus (HBV) surface antigen (HBsAg) or positive HBV core antibodies at Screening
19) Hepatitis C virus (HCV) antibodies and positive HCV RNA viral load (VL).
20) Serious active infection of any kind at Screening or Day 1
21) Blood loss (> 500 mL) or blood product transfusion within 12 weeks of Day 1
22) Known bleeding disorder or hypercoagulable state; antiphospholipid antibody syndrome with prior clinically significant event (per judgment of investigator); or on chronic anticoagulation or anti-platelet therapy
23) Current drug or alcohol abuse, or heavy tobacco use, as per judgment of investigator
24) Clinically significant laboratory values at Screening, including those listed in the protocol
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects fulfilling protocol-specified response criteria at Week 12, as compared to baseline.
Response is defined as follows: For subjects with elevated hsCRP (defined as ≥ 1.5 upper limit of normal (ULN) of hsCRP) at Day 1, subjects are considered to be a responder if they achieve all of the following :
- ≥ 20% improvement in hsCRP
- ≥ 20% improvement in at least 3 out of 5 subject reported, SjS related visual analog scales (VAS; subject’s assessment of global disease, pain, oral dryness, ocular dryness and fatigue)
- no worsening (defined as > 30 mm increase from baseline) in any of the above VAS
For subjects without elevated hsCRP (< 1.5 ULN of hsCRP) at Day 1, subjects are considered to be a responder if achieve all of the following:
- no increase ≥ 1.5 ULN of hsCRP
- ≥ 20% improvement in at least 3 out of 5 subject reported, SjS related VAS (subject’s assessment of global disease, pain, oral dryness, ocular dryness and fatigue)
- no worsening (defined as > 30 mm increase from baseline) in any of the above VAS |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Change from baseline in ESSDAI and ESSPRI at weeks 12 and 24 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | 4 |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 |
| Poland |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
