E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with active sight-threatening, non-infectious anterior, anterior and intermediate- or panuveitis who require systemic immunosuppression for the control of their disease. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046851 |
E.1.2 | Term | Uveitis |
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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 |
The objective of this study is to assess the safety and efficacy of LX211 as therapy in subjects with active sight-threatening, non-infectious anterior, anterior and intermediate- or panuveitis who require systemic immunosuppression for control of their disease. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A documented history of non-infectious anterior, anterior and intermediate or panuveitis. Subjects are anticipated to have, but are not restricted to, the following conditions: intermediate uveitis of the pars planitis subtype, sarcoidosis, the Vogt-Koyanagi-Harada (VKH) syndrome, birdshot retinochoroidopathy, retinal vasculitis, sympathetic ophthalmia and multifocal choroiditis with panuveitis.
• Currently uncontrolled uveitis for a minimum of 2 weeks despite use of oral and/or topical corticosteroid or subjects who are intolerant of local corticosteroid therapy due to the development of an ocular hypertensive response are eligible for inclusion or subjects with uncontrolled uveitis for whom oral corticosteroid is contraindicated.
• Subject has Grade 2+ or higher for anterior chamber cells at the time of enrollment.
• Subjects are considered by the investigator to require corticosteroid-sparing therapy. Reasons may include but are not limited to such considerations as exacerbation of previously controlled disease, need for steroid-sparing therapy, corticosteroid-intolerance, history of diabetes, adverse experiences with current therapy or conditions for which immunosuppressive therapy is used typically.
• The subject does not plan to undergo elective ocular surgery (e.g., cataract extraction) during the course of the study.
• The subject, whether male or female, with reproductive potential and who is sexually active agrees to use double-barrier contraception methods throughout the course of the study (minimum of 24 weeks).
• Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to starting study drug.
• Subject weighs at least 38 kg (84 lbs) and no more than 129 kg (284 lbs). (Note: this restriction is imposed to allow for the masking of treatment assignments.)
• Subjects or their guardians must be capable of understanding the purpose and risks of the study; able to give informed consent (and assent by pediatric subjects, if required) and to comply with the study requirements. |
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E.4 | Principal exclusion criteria |
• Age less than 13 years.
• Uveitis of infectious etiology.
• Clinically suspected or confirmed central nervous system or ocular lymphoma.
• Treatment with an immune suppression regimen that includes an alkylating agent within the previous 90 days.
• Subjects who have received treatment with a monoclonal antibody or any other biologic therapy within the previous 90 days or alemtuzumab within the previous 12 months.
• Presence of an ocular toxoplasmosis scar.
• History of herpes zoster or varicella infection within 6 weeks prior to enrollment, or chicken pox exposure within 21 days before enrollment.
• Seropositivity for human immunodeficiency virus (HIV).
• Alanine transaminase (ALT), aspartate transaminase (AST), or gammaglutamyl transferase (GGT) ≥ 3x upper limit of normal (ULN).
• Previous exposure or known contraindication to administration of LX211 (ISA247) or any of its components.
• Recipients of a solid organ transplant.
• History of clinically defined allergy to any of the constituents of the LX211 formulation (vitamin E, medium chain triglyceride oil, Tween 40, ethanol).
• Currently enrolled in another clinical therapeutic trial or who have received any investigational therapy within the 30 days prior to enrollment.
• Using a therapy for a condition other than uveitis that would likely affect immune responses or interfere with trial logistics.
• Currently pregnant or lactating.
• Active, extraocular infection requiring the prolonged or chronic use of antimicrobial agents or the presence of active hepatitis B or C.
• MDRD GFR < 60 mL/min
• Severe anemia (hemoglobin < 6 g/dL), leukopenia (WBC < 2500 mm3), thrombocytopenia (platelet count < 80,000 mm3), polycythemia (Hct > 54% [male] or Hct > 49% [female]) or clinically significant coagulopathy.
• Current malignancy or a history of malignancy (within the previous 5 years) except non-metastatic basal or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix that has been treated successfully.
• Any non-ocular co-morbid condition that would require immunosuppression or that would likely have an impact on the subject’s ability to comply with the study visit schedule.
• Any current or history of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the mean change from baseline in graded anterior chamber cells after 16 weeks of therapy or at time of rescue, if earlier. Subjects who experience either an increase of at least 1 grade from baseline at Visit 3 or show no improvement from baseline by Visit 4 are to receive rescue therapy. |
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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 | 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) | Yes |
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.8.3 |
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 | 10 |
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 | Information not present in EudraCT |
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 |
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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
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Last visit of last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |