| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Systemic Lupus Erythematosus (SLE) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Systemic Lupus Erythematosus ( SLE) also known as Lupus |
|
| 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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025139 |
| E.1.2 | Term | Lupus erythematosus systemic |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 long-term safety and tolerability of baricitinib in patients with SLE.
|
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD and background standard-of-care therapy on SLE disease activity
- To evaluate the long-term corticosteroid sparing effect of baricitinib 4-mg or 2-mg QD
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on SLE flares
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on mucocutaneous manifestations of SLE
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on musculoskeletal manifestations of SLE
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on individual organ system disease activity.
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on damage.
- To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on patient-reported outcomes (PROs) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[ [1] Are at least 18 years of age.
[2] Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
[3] Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 ACR criteria for classification of SLE (Tan et al. 1982; Hochberg et al. 1997) prior to randomization.
[4] Have 1 or more of the following as assessed by the central lab during screening: a positive antinuclear antibody (ANA; titer ≥1:80), and/or a positive anti-dsDNA, and/or a positive anti-Smith (anti Sm). Patients with an ANA <1:80 at screening with documentation of a historical ANA ≥1:80 may be eligible, as assessed by the eligibility review committee.
[5] Have a total SLEDAI-2K score ≥6 during screening, with at least 4 points attributed to clinical items (not including items requiring laboratory value assessment). SLEDAI-2K items requiring laboratory values should be assessed based on the results from the labs drawn during the screening period.
[6] Have a clinical SLEDAI-2K score ≥4 at baseline (Visit 2); not including any items requiring laboratory value assessment.
[7] Have at least 1 BILAG A score or 2 BILAG B scores during the screening period. BILAG items requiring laboratory values should be assessed based on the results from the labs drawn during the screening period.
[8] Are receiving at least one of the following SoC medications for SLE:
- A single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine) at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
- A single immunosuppressant (such as methotrexate [MTX], azathioprine, mycophenolate, tacrolimus, leflunomide, cyclosporine) at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
- An oral corticosteroid, initiated at least 4 weeks prior to screening (Visit 1), at a stable dose ≤40 mg/day prednisone (or equivalent) for at least 2 weeks prior to screening (Visit 1) and through baseline (Visit 2). If the patient is not receiving an antimalarial or immunosuppressant, the dose of corticosteroid must be ≥7.5 mg/day prednisone (or equivalent).
[9] Male or nonpregnant, nonbreastfeeding female patient
- Patients of child-bearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with the opposite sex.
- Total abstinence is defined as refraining from intercourse during the entirety of the study and for at least 1 week following the last dose of investigational product.
- Otherwise, patients of child-bearing potential must agree to use 2 effective methods of contraception, where at least 1 form is highly effective, for the entirety of the study and for at least 1 week following the last dose of investigational product.
- The following contraception methods are considered acceptable (the patient should choose 2, and 1 must be highly effective [defined as less than 1% failure rate per year when used consistently and correctly]):
• Highly effective birth control methods:
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
Progestogen-only containing hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
intrauterine device (IUD)/intrauterine hormone-releasing system (IUS)
vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate).
• Effective birth control methods:
Male or female condom with spermicide. It should be noted that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these methods are combined.
Diaphragm with spermicide
Cervical sponge
Cervical cap with spermicide
Patients of non‒child-bearing potential are not required to use birth control and they are defined as:
• Women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation)
• Post-menopausal – defined either as
A woman at least 50 years of age with an intact uterus
• Women aged 55 years or older who are not on hormone therapy, and who have had at least 6 months of spontaneous amenorrhea
• Women aged 55 years or older who have a diagnosis of menopause
[10] Must read and understand the informed consent approved by Eli Lilly and Company (Lilly), or its designee, and the institutional review board (IRB)/ethics review board (ERB) governing the site, and provide written informed consent.
|
|
| E.4 | Principal exclusion criteria |
[11] Have severe active lupus nephritis defined clinically and/or by histologic evidence of proliferative glomerulonephritis on renal biopsy (if available) within the 24 weeks prior to screening, or urine protein/creatinine ratio >200 mg/mmol (as an estimate of approximate proteinuria >2 g/day) or eGFR (Modification of Diet in Renal Disease [MDRD]) <40 mL/min/1.73 m 2 at screening, or as determined by the eligibility review committee.
[12] Have active CNS lupus as defined by ACR nomenclature for neuropsychiatric lupus syndromes and as captured by SLEDAI-2K (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, and cerebrovascular accident).
[13] Have active fibromyalgia that, in the investigator’s opinion, would make it difficult to appropriately assess SLE activity for the purposes of this study.
[14] Have been treated for or had an active occurrence of a systemic inflammatory condition other than SLE.
[15] Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the patient.
[16] Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient’s participation in the study.
[17] Have experienced any of the following within 12 weeks of screening: VTE (DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
[18] Have a history of recurrent (≥2) VTE (DVT/PE).
[19] Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness.
[20] Have a history of lymphoproliferative disease
[21] Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection or any other active or recent infection.
[22] Have symptomatic herpes simplex at the time of randomization.
[23] Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.
[24] Have a history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement).
[25] Have a positive test for hepatitis B virus (HBV)
[26] Have hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV ribonucleic acid [RNA]-positive).
[27] Have evidence of HIV infection and/or positive HIV antibodies.
[28] Have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB.
[29] Have evidence of active TB or latent TB
[20] Have a history of lymphoproliferative disease;
[21] Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection or any other active or recent infection.
[22] Have symptomatic herpes simplex at the time of randomization.
[23] Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.
[24] Have a history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement).
[25] Have a positive test for hepatitis B virus (HBV)
[26] Have hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV ribonucleic acid [RNA]-positive).
[27] Have evidence of HIV infection and/or positive HIV antibodies.
[28] Have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB.
[29] Have evidence of active TB or latent TB
[30] Have received parenteral corticosteroids within 6 weeks of screening (Visit 1), or are expected to require parenteral corticosteroids during the study.
[31] Have received any of the following medications (please refer to protocol).
[32] Have received a JAK inhibitor.
[33] Have been treated with probenecid that cannot be discontinued for the duration of the study.
[34] Have received plasmapheresis within 12 weeks of screening.
[35] Have been exposed to a live vaccine within 12 weeks of randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination).
[36] Are currently enrolled in or have discontinued within 4 weeks of screening from, any other clinical trial.
[37] Have previously completed or been randomized and withdrawn from this study or have received baricitinib in any other study.
[38] Have screening laboratory test values, in the opinion of the investigator, pose an unacceptable risk for the patient’s participation in the study.
[39] Have any of the following specific abnormalities on screening laboratory tests from the central laboratory (please refer to the protocol)
Other Exclusions (please refer to the protocol)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportion of patients with treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs).
Proportion of patients with temporary investigational product interruptions and permanent discontinuations.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The change will be evaluated from the baseline time point to the study week 156 time point |
|
| E.5.2 | Secondary end point(s) |
Proportion of patients achieving SRI-4 response through Week 156, defined as:
- Reduction of ≥4 points from baseline in SLEDAI-2K score; and
- No new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity score; and
- No worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician’s
Global Assessment of Disease Activity.
Proportion of patients achieving an SRI-5, -6, -7, or -8 response through Week 156.
Proportion of patients achieving an LLDAS response through Week 156.
Change from baseline in mean total SLEDAI-2Kscores through Week 156.
Change from baseline in Physician’s Global Disease Activity score through Week 156.
Proportion of patients receiving >7.5 mg prednisone (or equivalent) at baseline able to decrease dose by ≥25% to a prednisone equivalent dose of ≤7.5 mg/day maintained for at least 12 weeks through Week 156.
Change from baseline in prednisone dose through Week 156.
Proportion of patients taking corticosteroids at baseline able to discontinue use through Week 156.
Annualized mild/moderate flare rate
Annualized severe flare rate
Annualized flare rate (any severity).
Proportion of patients with CLASI total activity score ≥ 10 at baseline with ≥50% reduction in CLASI total activity score through Week 156.
Change from baseline in tender joint count through Week 156.
Change from baseline in swollen joint count through Week 156.
Proportion of patients with improvement in each SLEDAI-2K organ system versus baseline through Week 156.
Proportion of patients with worsening in each SLEDAI-2K organ system versus baseline through Week 156.
Change from baseline in SLICC/ACR damage index total score through Week 156.
Change from baseline in Worst Pain NRS through Week 156.
Change from baseline in Worst Joint Pain NRS through Week 156.
Change from baseline in Worst Fatigue NRS through Week 156.
Change from baseline in Patient Global Impression of Severity through Week 156.
Change from baseline in mental component score (MCS), physical component score (PCS), and domain scores in the Short-Form 36-item health
survey version 2 (SF- 36v2) acute through Week 156.
Change from baseline in FACIT-F total score through Week 156.
Change from baseline in the EQ-5D-5L through Week 156.
Change from baseline in the WPAI-Lupus through Week 156. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The change will be evaluated from the baseline time point to the study week 156 time 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 | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| 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 | 2 |
| 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 | 98 |
| 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 |
| Australia |
| Brazil |
| Chile |
| China |
| Colombia |
| India |
| Japan |
| Korea, Republic of |
| Mexico |
| Philippines |
| Russian Federation |
| Serbia |
| South Africa |
| Taiwan |
| United States |
| Austria |
| Belgium |
| Czechia |
| France |
| Germany |
| Hungary |
| Italy |
| Poland |
| Romania |
| Spain |
| Switzerland |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| End of the trial is the date of the last visit, last scheduled procedure shown in the Schedule of Activities, or date of discontinued participation for the last patient. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
Print
