| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Juvenile Idiopathic Arthritis Associated Uveitis or Anterior Antinuclear Antibody-Positive Uveitis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Eye inflammation associated with childhood arthritis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
| 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 | 10046851 |
| E.1.2 | Term | Uveitis |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this protocol is to evaluate the efficacy of baricitinib in children with JIA-U or ANA-positive uveitis |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are to:
-To evaluate the efficacy of baricitinib in children with JIA-U or ANA-positive uveitis in the most severely affected eye and less affected eye.
-To evaluate the efficacy of adalimumab in children with JIA-U or ANA-positive uveitis in the most severely affected eye and less affected eye.
-To evaluate the safety of baricitinib in children with JIA-U or ANA-positive children with JIA-U or ANA-positive uveitis
|
|
| 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 |
Protocol Addendum I4V-MC-JAHW version 1 dated 08-Mar-2019
An Open-Label, Active-Controlled, Safety and Efficacy Study of Oral Baricitinib in Patients from 2 Years to Less Than 18 Years Old with Active Juvenile Idiopathic Arthritis-Associated Uveitis or Chronic Anterior Antinuclear Antibody-Positive Uveitis.
This addendum allows for the radiographic assessment of paediatric patients with juvenile idiopathic arthritis (JIA)-associated uveitis (JIA-U) or chronic anterior antinuclear antibody (ANA)-postive uveitis participating in study I4V-MC-JAHW.
This addendum is optional. The purpose of the addendum is:
(1) To assess the effect of baricitinib on changes in bone erosion and joint space narrowing, as observed in hand/ wrist radiographs in a subgroup of patients in study JAHW.
(2) To assess the effect of baricitinib on bone growth in a subgroup of patients with JIA-U or chronic ANA-positive uveitis via hand/ wrist radiographs.
|
|
| E.3 | Principal inclusion criteria |
[1] Are at least 2 years and less than 18 years of age; full date of birth will be collected except in countries in which it is not allowed.
[2] Have a diagnosis of JIA U or chronic ANA positive uveitis without systemic features.
[3] Have active anterior uveitis, defined as cellular infiltrate in the anterior chamber of SUN criteria grade ≥1+ at Visit 1 (screening) and Visit 2 (potential randomization), despite prior treatment with adequate doses of topical steroid therapy and MTX.
[4] Have an inadequate response or intolerance to MTX (minimum dose of 10 mg/m2/week, with a maximum dose of 25 mg/m2/week). Patients considered to have inadequate response must have received MTX for at least 12 weeks before an inadequate response may be determined, and must have been on a stable dose for at least 4 weeks prior to screening if continuing MTX therapy during the study.
[5] Are receiving topical corticosteroid eye drops at a stable dose for at least 2 weeks prior to screening (maximum of 4 drops/day per eye at screening).
[6] Both a parent or legal guardian and the patient (as appropriate) are able to understand and fully participate in the activities of the study and sign their consent and assent, respectively, in accordance to local guidelines.
[7] Male or nonpregnant, nonbreastfeeding female patients
Patients of child-bearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) must agree to remain abstinent.
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, postovulation methods and withdrawal are not acceptable methods of contraception.
Otherwise, patients and their partners 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, and their partner, 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:
o Combined (estrogen- and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
o Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or implantable
o Intrauterine device/intrauterine hormone releasing system
o Vasectomized partner (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate).
• Effective birth control methods:
o 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.
o Diaphragm with spermicide
o Cervical sponge
o 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.
Adolescent females who have started menses (even 1 cycle and any amount of spotting) are considered to be of child-bearing potential.
Women of nonchild-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) and congenital anomaly such as mullerian agenesis.
|
|
| E.4 | Principal exclusion criteria |
[8] Have uveitis without a diagnosis of JIA or chronic anterior uveitis without positive ANA.
[9] Have a history or presence of any autoimmune inflammatory condition other than JIA, such as Crohn’s disease or ulcerative colitis.
[10] Have any contraindications to adalimumab as addressed in local product labeling or local clinical practice that would preclude the patient from participating in this study.
Exception: Patients who are bDMARD IR with a contraindication to adalimumab may be enrolled, as they will be assigned to baricitinib.
[11] Have increased intraocular pressure ≥25 mm Hg or that required treatment, including increases in medications, surgery, or hospitalization, within 4 weeks prior to baseline that, in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
[12] Have had intraocular surgery within the 3 months prior to screening (such as for cataract(s), glaucoma or vitrectomy).
[13] Are pregnant or breastfeeding. Prior to initiation of treatment, female patients of child-bearing potential must have a negative serum pregnancy test at the central laboratory during screening and a negative urine pregnancy test at Visit 2.
[14] Have a current or recent (<4 weeks prior to baseline) clinically serious 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.
[15] Have had an infection of bone or joint within 6 months prior to screening.
[16] Have symptomatic herpes simplex at baseline.
[17] Have had symptomatic herpes zoster infection within 12 weeks prior to baseline.
[18] Have a history of multidermatomal herpes zoster, or complicated herpes zoster (e.g., ocular or motor nerve involvement or disseminated herpes zoster such as systemic infection).
[19] Have a positive test for hepatitis B virus (HBV) at screening defined as:
a. positive for hepatitis B surface antigen (HBsAg), or
b. positive for hepatitis B core antibody (HBcAb) and positive for HBV deoxyribonucleic acid (DNA)
[20] Have hepatitis C virus (HCV) infection (hepatitis C antibody positive and confirmed presence of HCV ribonucleic acid [RNA]).
[21] Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies.
[22] Have had household contact with a person with active tuberculosis (TB) and did not receive appropriate and documented prophylaxis for TB.
[23] Have evidence of active TB or untreated/inadequately/inappropriately treated latent TB
a. Have evidence of active TB, defined in this study as the following:
• Positive PPD test (≥5 mm induration between approximately 48 and 72 hours after application, regardless of vaccination history), medical history, and clinical features.
• QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines) may be used instead of the PPD test. Patients are excluded from the study if the test is not negative and there is clinical evidence of active TB.
b. Have evidence of untreated/inadequately or inappropriately treated latent TB, defined in this study as the following:
• Positive PPD test, no clinical features consistent with active TB, and a chest x ray with no evidence of active TB at screening; or
• If the PPD test is positive and the patient has no medical history or chest x ray findings consistent with active TB, the patient may have a QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines). If the test results are not negative, the patient will be considered to have latent TB (for purposes of this study); or
• QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines) may be used instead of the PPD test. If the test results are positive, the patient will be considered to have latent TB. If the test is not negative, the test may be repeated once within approximately 2 weeks of the initial value. If the repeat test results are again not negative, the patient will be considered to have latent TB (for purposes of this study).
[24] Had 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.
[25] 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.
[26] Have a history of a VTE or are considered at high risk of VTE as deemed by the investigator.
[27] Are largely or wholly incapacitated, such as being bedridden.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the percentage of responders at Week 24. Response is defined according to the Standardization of Uveitis Nomenclature (SUN) criteria as a 2-step decrease in the level of inflammation (anterior chamber cells) or decrease to zero through week 24, in the eye most severely affected at baseline. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
-Change in SUN grade of cells in the anterior chamber through Week 24 in the most severely affected eye.
- Change in SUN grade of cells in the anterior chamber through week 24 in the less severely affected eye.
-Change in visual acuity by age-appropriate assessments through week 24.
-Change in vitreous haze through week 24.
-Change in grade of flare in the anterior chamber through week 24.
-Change in overall uveitis-related disability (assessment by parent and child VAS) through week 24.
-Proportion of patients with inactive anterior uveitis disease (using SUN definition) through Week 24.
-Time to inactive anterior disease (using SUN definition).
-Adverse events including serious adverse events.
-Change in SUN grade of cells in the anterior chamber through week 284 in the most severely affected eye.
-Change in SUN grade of cells in the anterior chamber through week 284 in the less severely affected eye.
-Change in visual acuity by age-appropriate assessments through week 284.
-Change in vitreous haze through Week 284.
-Change in grade of flare in the anterior chamber through week 284.
-Change in overall uveitis-related disability through week 284. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 |
| France |
| Germany |
| Italy |
| Spain |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 18 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 6 |
Print
