i
Submitted by: Abigail Tuazon 2019-09-03 04:46:42 Last Updated by: Principe, Jeverly Ann S 2019-09-30 17:00:47


Lupus Study

PHRR190930-002191

I4V-MC-JAIA

2018-CT0464

Protocol I4V-MC-JAIA(a): A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a chronic, often debilitating, multisystem, autoimmune disease
that is characterized by the presence of autoreactive B cells and elevated autoantibodies, which
directly damage the body’s cells and tissues. Systemic lupus erythematosus can affect multiple
organ systems simultaneously or sequentially, and follows a highly variable clinical course
where periods of relatively stable disease are followed by flares and/or periods of persistently
active disease; all of which can ultimately lead to irreversible damage to tissues and organ
systems.
Baricitinib is an oral, reversible, selective inhibitor of Janus kinase (JAK)1 and JAK2 (Fridman
et al. 2010). This activity profile suggests that baricitinib may inhibit cytokines implicated in
SLE, most notably type I interferon (IFN; JAK1/tyrosine kinase [TYK]2), interleukin (IL-6;
JAK1/JAK2/TYK2), and type II IFNγ, as well as other cytokines that may have a role in SLE,
including IL-23 (JAK2/TYK2), granulocyte–-macrophage colony stimulating factor
(JAK2/JAK2) and IL-12 (JAK2/TYK2). In a recently completed Phase 2 study (I4V-MC-JAHH
[JAHH]), baricitinib demonstrated clinical efficacy in patients with SLE. Baricitinib plus
standard of care was superior to placebo plus standard of care in the proportion of patients
achieving remission of rash and/or arthritis as defined by the Systemic Lupus Erythematosus
Disease Activity Index 2000 (SLEDAI-2K), as well as the proportion of patients achieving a
Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at Week 24.
Given the efficacy of baricitinib demonstrated in clinical trials for treating
autoimmune/autoinflammatory diseases involving joints, skin, and kidney (including SLE), the
acceptable safety profile of baricitinib observed through the current stage of development, and a
continuing unmet medical need in patients with SLE, there is a compelling rationale for the
initiation of a Phase 3 program to evaluate baricitinib in treatment of SLE.

Regime Classification Priority
2017 - 2022 Research to enhance and extend healthy lives Non-communicable diseases
Start Date Duration in Months Target Completion Date Actual Completion Date
2019-03-26 62 2024-05-26 0000-00-00

Ongoing

Institution Classification Region LTO #
Eli Lilly and Company Private Business United States of America LTO-3000002863828
Institution Classification Region LTO #
PPD Pharmaceutical Development Philippines Corporation Private Business NCR LTO-3000002863828
Institution Region
Eli Lilly and Company United States of America
Name E-Mail Institution and Institution Address
Cianele Nyeli Israel-Padua Cianele.Padua@ppdi.com 22nd Floor Net Park Building, 5th Avenue, E-Square, Crescent Park West, Bonifacio Global City, Taguig City, Manila, Philippines 1634
Name E-Mail Institution and Institution Address
Seema Sunil Seema.Sunil@ppdi.com Homebased Mumbai, India
Name Expertise Affiliation
Allan E. Lanzon, MD Mary Mediatrix Medical Center Mary Mediatrix Medical Center
Andrei Rhoniel M. Rodriguez, MD Makati Medical Center Makati Medical Center
Edgar Ramiterre, MD Southern Philippines Medical Center Southern Philippines Medical Center
Harold Michael P. Gomez, MD Angeles University Foundation Medical Center Angeles University Foundation Medical Center
James Bermas, MD Chong Hua Hospital Chong Hua Hospital
Merle Y. Barba, MD Cebu Doctors University Hospital Cebu Doctor's University College of Medicine
Sandra Navarra, MD St. Luke's Medical Center St. Luke's Medical Center - Quezon City
Project Location Institutional Ethics Review Board
Mary Mediatrix Medical Center Mary Mediatrix Medical Center Research Ethics Review Committee
Makati Medical Center Makati Medical Center Institutional Review Board
Southern Philippines Medical Center DOH XI Cluster Ethics Review Committee
Angeles University Foundation Medical Center Angeles University Foundation Medical Center Institutional Ethics Review Committee
Chong Hua Hospital Chong Hua Hospital Institutional Review Board
Cebu Doctor's University College of Medicine Cebu Doctors’ University Hospital Research Ethics Committee
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board

systemic lupus erythematosus (SLE)

Primary Objective:

To evaluate the effect of baricitinib 4-mg QD and
background standard-of-care (SoC) therapy compared
with placebo and SoC on SLE disease activity.

Primary Endpoint:

Proportion of patients achieving an SRI-4 response at
Week 52, 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.

Major Secondary Objective and endpoint

 To evaluate the effect of baricitinib 4-mg QD plus
SoC compared to placebo plus SoC on SLE
disease activity.
 Proportion of patients achieving an SRI-4 response
at Week 24.
 Proportion of patients achieving a lupus low disease
activity state (LLDAS) response at Week 52.
 To evaluate the corticosteroid sparing effect of
baricitinib 4-mg QD plus SoC compared to
placebo plus SoC.
 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 between Week 40 and
Week 52.
 To evaluate the effect of baricitinib 4-mg QD plus
SoC compared to placebo plus SoC on SLE
flares.
 Time to first severe flare over 52 weeks.
 To evaluate the effect of baricitinib 4-mg QD plus
SoC compared to placebo plus SoC on
patient-reported outcomes (PROs).
 Change from baseline in Worst Pain NRS at Week
52.
 Change from baseline in FACIT-Fatigue total score
at Week 52.
 To evaluate the effect of baricitinib 2-mg QD plus
SoC compared to placebo plus SoC on SLE
disease activity.
 Proportion of patients achieving an SRI-4 response
at Week 52.
 Proportion of patients achieving an SRI-4 response
at Week 24.
 Proportion of patients achieving a lupus low disease
activity state (LLDAS) response at Week 52.
 To evaluate the corticosteroid sparing effect of
baricitinib 2-mg QD plus SoC compared to
placebo plus SoC.
 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 between Week 40 and
Week 52.
 To evaluate the effect of baricitinib 2-mg QD plus
SoC compared to placebo plus SoC on SLE
flares.
 Time to first severe flare over 52 weeks.
 To evaluate the effect of baricitinib 2-mg QD plus
SoC compared to placebo plus SoC on
patient-reported outcomes (PROs).
 Change from baseline in Worst Pain NRS at Week
52.
 Change from baseline in FACIT-Fatigue total score
at Week 52

Recruiting

  • Argentina
  • Belgium
  • Bosnia and Herzegovina
  • Chile
  • Colombia
  • Czech Republic
  • France
  • India
  • Italy
  • Japan
  • Mexico
  • Philippines
  • Poland
  • Romania
  • Singapore
  • South Korea
  • Spain
  • United States

Clinical Trial

I4V-MC-JAIA

20180921140701

2019-03-26

0000-00-00

Unspecified

Unspecified

recruitment and screening is ongoing

26 Mar 2019

6.1. Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria:
Type of Patient and Disease Characteristics
[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 with documentation of a historical ANA ≥1:80 may be eligible, as assessed by the
eligibility review committee.
Note: The ANA, anti-dsDNA, and anti-Smith measurements may be repeated by
the central lab once during the screening period, and the value resulting from
repeat testing may be accepted for enrollment eligibility if it meets the eligibility
criterion.
[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.
I4V-MC-JAIA(a) Clinical Protocol Page 36
LY3009104
Prior/Concomitant Therapy
[8] Are receiving at least one of the following SoC medications for SLE:
a. A single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine)
at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
b. 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).
c. 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).
Patient Characteristics
[9] 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 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.
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 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, intravaginal, or transdermal
 intrauterine device (IUD)/intrauterine hormone-releasing system
(IUS)
I4V-MC-JAIA(a) Clinical Protocol Page 37
LY3009104
 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 either
o Cessation of menses for at least 1 year
o At least 6 months of spontaneous amenorrhea with
follicle-stimulating 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
[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

 

 

6.2. Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
Medical Conditions
[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]) the eligibility review committee.
Note: The lab measurements related to lupus nephritis may be repeated once by
the central lab during the screening period, and the values resulting from repeat
testing may be accepted for enrollment eligibility if they meet the eligibility
criterion.
[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 such as, but not limited to, RA, juvenile chronic
arthritis, spondyloarthropathy, Crohn’s disease, ulcerative colitis, or psoriatic
arthritis within the 12 weeks prior to screening. Patients with secondary
Sjögren’s syndrome are not excluded.
[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.
[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 that in the opinion of the investigator, could
constitute an unacceptable risk when taking investigational product or interfere
with the interpretation of data.
I4V-MC-JAIA(a) Clinical Protocol Page 39
LY3009104
[20] Have a history of lymphoproliferative disease; have signs or symptoms suggestive
of possible lymphoproliferative disease, including lymphadenopathy or
splenomegaly (other than primarily due to SLE); have active primary or recurrent
malignant disease; or have been in remission from clinically significant
malignancy for The following may be exempted:
a. Patients with cervical carcinoma in situ that has been resected with no evidence of
recurrence or metastatic disease for at least 3 years may participate in the study.
b. Patients with basal cell or squamous epithelial skin cancers that have been completely
resected with no evidence of recurrence for at least 3 years may participate in the
study.
[21] Have a current or recent (viral, bacterial, fungal, or parasitic infection or any other active or recent infection
that in the opinion of the investigator, would pose an unacceptable risk to the
patient if participating in the study.
Note: For example, a recent viral upper respiratory tract infection or
uncomplicated urinary tract infection need not be considered clinically serious.
[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) defined as:
a. positive for hepatitis B surface antigen (HBsAg), or
b. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B
virus deoxyribonucleic acid (HBV DNA)
Note: Patients who are HBcAb-positive and HBV DNA-negative may be
enrolled in the study but will require additional HBV DNA monitoring during
the study.
[26] Have hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV
ribonucleic acid [RNA]-positive).
Note: Patients who have documented anti-HCV treatment for a past HCV
infection AND are HCV RNA-negative may be enrolled in the study.
[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

Interventional

Rheumatology

Systemic lupus erythematosus is a chronic, often debilitating, multisystem, autoimmune disease
that is characterized by the presence of autoreactive B cells and elevated autoantibodies, which
directly damage the body’s cells and tissues. Systemic lupus erythematosus can affect multiple
organ systems simultaneously or sequentially, and follows a highly variable clinical course
where periods of relatively stable disease are followed by flares and/or periods of persistently
active disease; all of which can ultimately lead to irreversible damage to tissues and organ
systems.

Date Amendment Classification Reason
2019-06-18 Amendments related to the protocol Statistical analysis
2019-06-18 Amendments related to the protocol Inclusion criteria

Randomized

Double Blind

Unspecified

Parallel

To evaluate the effect of baricitinib 4-mg QD and
background standard-of-care (SoC) therapy compared
to placebo and SoC on SLE disease activity.

Phase II/III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
©2021 HERDIN PLUS. All rights reserved. | Contact Us | Keep up to date