| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active Non-infectious Anterior Uveitis including Uveitic Glaucoma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
| MedDRA Classification |
| 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 study is to evaluate the efficacy and safety of TRS01 1.0% eye drops compared to prednisolone acetate 1.0% ophthalmic suspension in subjects with active non-infectious anterior uveitis with or without uveitic glaucoma |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion criteria:
A subject must meet all of the following criteria in order to be eligible for the study:
1.At sites in the US: Male or female up to and including 70 years of age(including all pediatric age groups). At sites in the EU: Male or femalebetween 18 and 70 years of age, inclusive.
2.Able to provide informed consent/assent, or subject’s Legally AuthorizedRepresentative (LAR) provide consent, follow instructions and complete allrequired study visits for the duration of the study.
3.Diagnosed with active non-infectious anterior uveitis with anterior chambercell Grade 2 (6-15 cells) or Grade 3 (16-30 cells) in the study eye that arewithout any treatment or with Stable Medical Therapy (as defined below)requiring further treatment.
4.Have BCVA ≥ 65 letters in the non-study eye using Early TreatmentDiabetic Retinopathy Study (ETDRS).
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5. Use adequate birth control by men and women, if of reproductive potential and sexually active. If a female subject is currently abstinent, they must agree to use one of the acceptable methods of birth control before they become sexually active. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 14 days after the last study visit.
a. For females of childbearing potential, adequate birth control methods will be defined as hormonal contraceptives or intrauterine device initiated at least 60 days prior to Visit 1, or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam.
b. For males with partners who are of child-bearing potential, adequate birth control methods will be defined as double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam or have had a vasectomy for at least 60 days prior to Visit 1.
c. For postmenopausal females, menopause is defined as one year without menses; if in question, a follicle-stimulating hormone of > 40 IU/L must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least 60 days prior to Visit 1 must be documented, as applicable.
Stable Medical Therapy: Permitted Stable Medical Therapy includes the following systemic or topical therapies, for uveitis or other underlying disease or condition:
•Systemic immunosuppressive therapy (e.g., methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, or adalimumab) that is initiated and stable for at least 60 days prior to Visit 1 and with a stable dose regimen continued throughout the IP treatment period (through Visit 5).
•Systemic steroids ≤15 mg/day that are initiated and stable for at least 45 days prior to Visit 1 and with a stable dose regimen continued throughout the IP treatment period (through Visit 5).
•One drop per day of a topical ocular corticosteroid (excluding difluprednate [Durezol®]) that is initiated and stable for at least 30 days prior to Visit 1 and with a stable dose regimen continued throughout the IP treatment period (through Visit 5) in the study eye. |
|
| E.4 | Principal exclusion criteria |
Exclusion criteria:
A subject who meets any of the following criteria is not eligible for the study:
1. Pregnant or breastfeeding females or females with a positive pregnancy test at Visit 1.
2.Have a history of or active significant ocular disease in either eye that, basedon the Investigator’s judgement, could confound the results of the trialincluding, but not limited to:
a.Infectious uveitis
b.Active intermediate uveitis (including vitritis), posterior uveitis(including chorioretinitis) or panuveitis
c.Traumatic or post-surgery uveitis
d.Any disease that may require an intraocular injection during thestudy
e.Grade 4 ACC and/or the presence of a hypopyon and/or Grade 4Anterior Chamber Flare
f.Dry eye disease requiring greater than QID dosing with artificialtears
g.Based on past uveitis treatment history and/or Investigator’sdiscretion, the subject is anticipated to require initiation oradditional treatment with systemic steroids during the study
3.Uncontrolled intraocular pressure (IOP) (defined as >27mmHg) or narrowangle glaucoma in either eye and/or are at risk of angle closure with dilating.Glaucoma medications, if administered, must be stable for at least 30 daysprior to Visit 1 and throughout the study.
4.Have poor posterior view due to limitation of dilation or media opacity thatlimits ability to examine the posterior segment.
5.Have cancer or melanoma that is actively treated with immunotherapy.
6.Have any clinically significant systemic disease or condition (e.g.,hematological, cardiovascular, respiratory, renal diseases) that, in theInvestigator's opinion, may confound the trial results, pose a safety risk tothe subject or preclude the subject from adhering to the protocol orcompleting the trial per protocol, or instilling eye drops.
7.Have a known history of alcohol and/or drug abuse within 5 years prior toVisit 1.
8.Use of contact lenses in the study eye, during the study.
9.Be an employee of the site that is directly involved in the management,administration, or support of this study or be an immediate family memberof the same.
10.Currently participating or having participated in another clinical trial withthe investigational product, TRS01.
11.Use of the following medications and procedures in the study eye areprohibited within the excluded timeframe prior to Visit 1 as defined belowand through the end of the study (Visit 6), unless otherwise noted. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoint:
The hierarchical approach will be adopted for the primary and secondary endpoints. The study has a single primary efficacy endpoint that differs by region. The following primary endpoint will be analyzed first and only if the null hypothesis is rejected will the secondary endpoints be tested.
1. For Food and Drug Administration (FDA) submission, the proportion of subjects with ACC Grade = 0 (0 cells) on Day 28 in the study eye.
2. For submission to European Medicines Agency (EMA) related countries, the proportion of subjects with ACC Grade = 0 or 1 on Day 28 in the study eye. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Approximately 6 weeks (42 ± 3 days): 28-day treatment period and 14-day follow-up period. |
|
| E.5.2 | Secondary end point(s) |
Secondary Endpoints:
Secondary Endpoints:
To control type I error for secondary endpoints, the hierarchy for the secondary endpoints begins with the powered secondary endpoint and then proceeds to the key secondary endpoints in order. Other secondary endpoints will be evaluated to support the primary, powered secondary, and key secondary endpoints.
Powered Key Secondary Efficacy Endpoint: The powered key secondary endpoint is the change from baseline in ACC Grade on Day 28 in the study eye.
Key Secondary Endpoints:
1. For FDA submission: Proportion of subjects with ACC Grade = 0 on Day 21 in the study eye. For submission to EMA related countries: Proportions of subjects with ACC Grade = 0 or 1 on Day 21 in the study eye.
2. Change from baseline in ACC Grade on Day 21.
Other Secondary Efficacy Endpoints:
1. The time from baseline to ACC grade = 0 (FDA submission) or ACC grade = 0 or 1 (for submission to EMA related countries);
2. The proportion of subjects with grade = 0 for anterior chamber flare, ocular pain, or ocular photophobia on Day 28;
3. The change from baseline in anterior chamber flare, ocular pain, or ocular photophobia grades on Day 28;
4. The proportion of subjects with grade = 0 for anterior chamber flare, ocular pain, or ocular photophobia on Day 21;
5. The change from baseline in anterior chamber flare, ocular pain, or ocular photophobia grades on Day 21;
6. The time from baseline to pain grade = 0;
7. The proportion of subjects who receive rescue treatment; and the time from baseline to rescue treatment.
Exploratory endpoints are listed in Section 2.2.3.
Safety Endpoints: The following safety endpoints will be evaluated and summarized:
•Incidence of adverse events (AEs), serious adverse events (SAEs) andcomplications by severity and relationship to investigational productoccurring during the study.
•Best corrected visual acuity (BCVA)
•Slit-lamp biomicroscopy
•Dilated ophthalmoscopy
•Change in ocular signs and symptoms including 1) corneal and conjunctivaltolerability as assessed by the incidence of ocular treatment-related AEs and2)intraocular pressure.
•Number and percentage who fail to complete the study due to lack ofefficacy (need for rescue).
•Treatment tolerability by number and percentage of subjects who fail tocomplete the study due to an AE related to Investigational Product (IP) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Approximately 6 weeks (42 ± 3 days): 28-day treatment period and 14-day follow-up period. |
|
| 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 | No |
| 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) | 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| 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 |
| Germany |
| United States |
| France |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| Last visit of the 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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