E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with active sight-threatening, non-infectious anterior uveitis who require systemic immunosuppression for 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 evaluate the safety and efficacy of LX211 as treatment and maintenance therapy in subjects with active sight-threatening, non-infectious anterior uveitis 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 |
• Subjects with a documented history of non-infectious anterior, anterior and intermediate, or pan-uveitis
• Uncontrolled uveitis, as evidenced by Grade 2+ or higher anterior chamber cells, in at least one eye for ≥ 2 weeks prior to randomization
• In subjects whose diagnosis is not exclusively anterior uveitis, the predominant manifestation of their condition at the time of enrollment must be anterior segment inflammation
• Current uveitis therapy must conform to one of the following: • Prednisone monotherapy at a dose of ≥ 10 mg/day (or equivalent) for ≥ 2 weeks prior to randomization • Have received ≥ 2 injections of corticosteroid (intravitreal or periocular) for control of disease within the past 8 months, but not within 2 weeks of randomization; subjects may also be receiving systemic corticosteroid therapy • Receiving monotherapy with azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate for at least 2 weeks prior to randomization • Receiving prednisone in addition to one immunomodulatory agent from among cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid and methotrexate for at least 2 weeks prior to randomization • Subjects for whom corticosteroid therapy (systemic or local) is medically inappropriate or who refuse corticosteroid therapy
• Considered by the Investigator to require immunomodulatory therapy
• Subject does not plan to undergo elective ocular surgery (e.g., cataract extraction) during the study
• A minimum ability to count fingers at a distance of 30 cm (1 foot) using the study eye
• At least 18 years of age
• Subjects, whether male or female, with reproductive potential and who are sexually active agree to use double-barrier contraception methods throughout the course of the study (minimum of 24 weeks) and throughout the extension phase
• Women of childbearing potential must have a negative urine pregnancy test (UPT) within 48 hours prior to starting study drug and must not be lactating
• Female subjects of non-childbearing potential must meet at least one of the following criteria: • Be over the age of 60 years • Be amenorrheic for at least 2 years if age 45-60 years • Have had a hysterectomy and/or bilateral oophorectomy
All other female subjects (including those with tubal ligations) will be considered to be of childbearing potential
• Subjects must weigh at least 38 kg (84 lbs) and no more than 110 kg (242 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) • Able to comply with the study requirements |
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E.4 | Principal exclusion criteria |
• Uveitis of infectious etiology
• Clinically suspected or confirmed central nervous system or ocular lymphoma
• Uncontrolled glaucoma, as evidenced by an intraocular pressure of > 21 mmHg while on medical therapy
• Subjects with chronic hypotony (less than 6 mmHg)
• Any implantable corticosteroid-eluting device (e.g., Retisert™, Posurdex®, Medidur™, I-vation™ TA intravitreal implant)
• 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 30 days or alemtuzumab within the previous 12 months
• Subjects who have used any drugs or substances known to be strong inhibitors of CYP 3A4/5 enzymes within 7 days of the first dose, or grapefruit juice and star fruit within 24 hours of the first dose
• Subjects who have taken any other medications listed in Section 9.7 of the protocol, within the timeframe specified, prior to the first dose
• Presence of an ocular toxoplasmosis scar
• A known history or clinical diagnosis of herpes zoster or varicella infection within 6 weeks before enrollment, or chicken pox exposure within 21 days before to enrollment
• Seropositivity for human immunodeficiency virus (HIV)
• Alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyl transferase (GGT) ≥ 3x upper limit of normal
• Previous exposure or known contraindication to administration of LX211 (ISA247) or any of its components (vitamin E, medium chain triglyceride [MCT] oil, polysorbate 40, ethanol)
• Recipients of a solid organ transplant
• Currently enrolled in another clinical therapeutic trial or who have received any investigational therapy within the 30 days prior to enrollment and/or has not recovered from any reversible effects or side effects of prior investigational agent
• Using a therapy that would likely affect immune responses or interfere with trial logistics
• Active, extraocular infection requiring the prolonged or chronic use of antimicrobial agents or the presence of active hepatitis A, B or C (HAV, HBV, HCV)
• Subjects who have a history of or exposure to syphilis or Lyme disease
• Modification of Diet in Renal Disease Study (MDRD) glomerular filtration rate (GFR) < 60 mL/min
• Severe anemia (hemoglobin < 6 g/dL), leukopenia (white blood cell count < 2500/mm3), thrombocytopenia (platelet count < 80,000/mm3), polycythemia (hematocrit > 54% [male] or hematocrit > 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
• Subjects with any non-ocular, medically significant co-morbid conditions that impair normal activities, require immunosuppression, or any medical condition that would likely have an impact on the participant’s ability to comply with the study visit schedule
• Currently pregnant or lactating
• Any current or history of substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results |
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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 AC cells at 16 weeks of therapy or at time of rescue, if earlier.
If statistically significance is achieved for graded AC cells at 16 weeks, mean change from baseline in graded AC cells at 24 weeks ot therapy or at time of rescue, if earlier, will also be analyzed as a primary endpoint.
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |