| 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 |
Patients are eligible to be included in the study only if they meet all of
the following criteria at
screening:
Type of Patient and Disease Characteristics
[1] Have completed the final treatment study visit of an originating
study, such as Study JAHZ or Study JAIA. Patient Characteristics
[2] Male or nonpregnant, nonbreastfeeding female patient
a. Patients of child-bearing potential who are abstinent (if this is complete
abstinence, as their preferred and usual lifestyle) or in a samesex
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.
b. 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. Periodic abstinence, such as calendar,
ovulation, symptothermal, post-ovulation methods, and withdrawal, are
not acceptable methods of contraception.
c. Otherwise, patients of childbearing potential together with their
partners 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.
d. 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, injectable, or implantable
Intrauterine device (IUD)/intrauterine hormone-releasing system
(IUS)
Vasectomized male (with appropriate post-vasectomy 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
Note: When local guidelines concerning highly effective or effective
methods of birth control differ from the above, the local guidelines must
be followed.
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, not on
hormone therapy, who has had either
Cessation of menses for at least 1 year
At least 6 months of spontaneous amenorrhea with folliclestimulating
hormone >40 mIU/mL
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
Informed Consent
[3] 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.
Change from baseline in prednisone dose 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
| Information not present in EudraCT |
| 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 | 3 |
| 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 |
| Austria |
| Belgium |
| Brazil |
| Chile |
| China |
| Colombia |
| Czech Republic |
| France |
| Germany |
| Hungary |
| India |
| Italy |
| Japan |
| Korea, Republic of |
| Mexico |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| South Africa |
| Spain |
| Switzerland |
| Taiwan |
| United Kingdom |
| United States |
|
| 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 |
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