i
Submitted by: Ms. Myra Ann Uy 2020-04-30 06:23:38 Last Updated by: Ms. Myra Ann Uy 2020-12-16 09:41:05


Lupus Study (Extension Study)

PHRR200820-002639

I4V-MC-JAIM

2019-CT0501

A Phase 3, Double-Blind, Multicenter Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Patients with Systemic Lupus Erythematosus (SLE)

 

Systemic lupus erythematosus (SLE) 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 the 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
2020-08-27 40 2023-12-27 0000-00-00

Pending

Although Clinical Trial has been approved earlier, roll-over of patients from the originating study is estimated to happen in August 2020

Institution Classification Region LTO #
Eli Lilly and Company Private Business United States of America LTO-3000002863828
Institution Region
Eli Lilly and Company United States of America
Name E-Mail Institution and Institution Address
Cianele Nyeli Israel-Padua Israel-Padua Cianele.Padua@ppdi.com PPD 20/F Seven/NEO Building (formerly Net Park Building) 5th Avenue, E-Square, Crescent Park West Bonifacio Global City, Taguig, Philippines 1634
Name E-Mail Institution and Institution Address
Debra Ho Debra.Ho@ppdi.com Homebased, Hong Kong
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 Doctors' University Hospital
Sandra Teresa V. 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 Doctors' University Hospital Cebu Doctors' University Hospital - Institutional Ethics Review 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 long-term safety and tolerability of baricitinib in patients with SLE.

Primary Outcome

Safety and tolerability assessments will include:
 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.

Secondary Objectives

Objective:
 To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD and background standard-of-care therapy on SLE disease activity.

Outcomes:

 Proportion of patients achieving SRI-4 response through Week 156, defined as:
o Reduction of ≥4 points from baseline in SLEDAI-2K score; and
o No new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity score; and
o 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-2K scores through Week 156.
 Change from baseline in Physician’s Global Disease Activity score through Week 156.

Objective: To evaluate the long-term corticosteroid sparingeffect of baricitinib 4-mg or 2-mg QD.

outcomes: 

  • 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.

Objective: To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on SLE flares.

Outcome: 

  • Annualized mild/moderate flare rate
  • Annualized severe flare rate
  • Annualized flare rate (any severity).

Objective:To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on mucocutaneous manifestations of SLE.

Outcome: Proportion of patients with CLASI total activity score ≥ 10 at baseline with ≥50% reduction in CLASI total activity score through Week 156.

Objective: To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on musculoskeletal manifestations of SLE.

outcome: Change from baseline in tender joint count through
Week 156.
 Change from baseline in swollen joint count through
Week 156.

Objective: To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on individual organ system disease
activity.

outcomes: 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.

Objective: To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on damage.

Outcome: Change from baseline in SLICC/ACR damage index total score through Week 156.

Objective:To evaluate the long-term effect of baricitinib 4-mg or 2-mg QD on patient-reported outcomes (PROs).

Outcomes: 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.

 

Recruiting

  • Argentina
  • Australia
  • Austria
  • Belgium
  • Brazil
  • Chile
  • China
  • Colombia
  • Czech Republic
  • France
  • Germany
  • Hungary
  • India
  • Italy
  • Japan
  • Mexico
  • Philippines
  • Poland
  • Romania
  • Russia
  • Serbia
  • South Africa
  • South Korea
  • Spain
  • Switzerland
  • Taiwan
  • United Kingdom
  • United States

Clinical Trial

I4V-MC-JAIM

Unspecified

2019-08-19

0000-00-00

37

Unspecified

Unspecified

27 Aug 2020

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 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 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, intravaginal, or transdermal

 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.

ents of non‒child-bearing potential are not required to use birth control and 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 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

[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.

Exclusion Criteria
Medical Conditions

[4] Have significant uncontrolled cerebro-cardiovascular (for example, myocardial infarction, unstable angina, unstable arterial hypertension, severe heart failure, or cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or abnormal laboratory values that, in the opinion of the investigator, pose an unacceptable risk to the patient if investigational product continues to be administered.

[5] Have a known hypersensitivity to baricitinib or any component of this investigational product.

[6] Had investigational product permanently discontinued at any time during a previous baricitinib study.

[7] Had temporary investigational product interruption at the final study visit of a previous baricitinib study and, in the opinion of the investigator, this poses an unacceptable risk for the patient’s participation in the study.

[8] Have any other condition that, in the opinion of the investigator, renders the patient unable to understand the nature, scope, and possible consequences of the study or precludes the patient from following and completing the protocol.

[9] Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research, judged not to be scientifically or medically compatible with this study.

Interventional

Rheumatology

Systemic lupus erythematosus (SLE) 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 the treatment of SLE.

None

Randomized

Double Blind

Unspecified

Parallel

To evaluate the long-term safety and tolerability of baricitinib in patients with SLE.

Phase III

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