Anterior Uveitis, Clinically Significant Macular Edema, Intermediate Uveitis, Posterior Uveitis, Scleritis, Uveitis
Conditions
Keywords
Glaucoma associated with uveitis
Brief summary
Uveitis represents a heterogeneous group of diseases that results from ocular inflammatory reaction involving ocular tissue and vasculature. The inflammation usually causes pain, redness, photophobia and blurred vision. This inflammation, is typically treated with regional or systemic therapy. The regional therapy typically consists of topical corticosteroids or periocular or regional corticosteroids. Regional therapy can lead to a steroid response glaucoma, which is increased intraocular pressure.This pilot study aims to evaluate the possible effectiveness of H.P. Acthar in patients with active ocular inflammatory disease, and currently on treatment for glaucoma or have a history of glaucoma.
Detailed description
Uveitis represents a heterogeneous group of diseases that results from ocular inflammatory reaction involving ocular tissue and vasculature. The inflammation usually causes pain, redness, photophobia and blurred vision. H.P Acthar Gel stimulate the adrenal cortex to secrete cortisol. Additionally H.P. Acthar gel is also reported to bind to melanocortin receptors. Melanocortin receptor activation has been shown to exert marked anti-inflammatory and immune-modulatory effects in animal studies, by modulating pro inflammatory cytokines, followed by induction of anti- inflammatory mediators and subsequent leukocyte migration. Specifically melanocortins down regulate Tumor Necrosis Factor (TNF) alpha, Interleukin (IL) -2, Interferon gamma and T-cell proliferation and upregulates IL-10 and regulatory T cells. For this reason H.P. Acthar is an approved treatment for ocular inflammatory disease. Ocular inflammatory disease is typically treated with regional or systemic therapy. The regional therapy typically consists of topical corticosteroids or periocular or regional corticosteroids. Regional therapy can lead to a steroid response glaucoma, which is increased intraocular pressure.This pilot study aims to evaluate the possible effectiveness of H.P. Acthar in patients with active ocular inflammatory disease, and currently on treatment for glaucoma or have a history of glaucoma. Subjects will be treated with H P Acthar subcutaneous gel, 40 U/ml, given twice weekly x 8 weeks, followed by once weekly x 4 weeks: a total 20 doses with the same cumulative units to be administered, using the approved route, with the option to do 4 additional doses if resolution is incomplete. This will be a prospective open-label, non-randomized pilot study: 12 week treatment for active non-infectious uveitis, endpoint assessment and safety assessment; additional 12 week assessment for uveitis activity/quiescence and safety assessment.
Interventions
DRUGH.P. ACTHAR SUBCUTANEOUS GEL INJECTION
Subcutaneous injection twice weekly
Sponsors
Mallinckrodt
Tampa Bay Uveitis Center, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has the ability to understand and sign the informed consent document * Subject is 18 years of age or older * Subject can be male or female * Subject has negative Purified Protein Derivative (Tuberculosis skin test) or quantiferon TB Gold Test (blood test for TB) testing done in 3 months * Subject has active ocular inflammation in at least one eye * Subject has visual acuity in at least one eye of 20/400 or better. * Subject has a history of glaucoma or has actively treated glaucoma * Subject is willing and able to comply with the study procedures * Female subjects of childbearing potential must not be pregnant or breast-feeding, must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing throughout the study
Exclusion criteria
* Subject has any ocular infection * Subject has any systemic infection * Participant has documented immunocompromised or immune-incompetent state * Subject has any ocular co-morbidity than prevents assessment of intraocular inflammation * Subject has had any intra-ocular surgery in previous 6 weeks * Subject has any planned elective surgery ocular or systemic during study duration * Subject is pregnant or breast-feeding * Subject had a recent vaccination with live or attenuated vaccines * Subject has a sensitivity to Porcine derived proteins * Subject has a medical history which is a contraindication to receiving H.P. Acthar
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography | 12 Weeks | Subjects will have fundus photography at baseline and 12 weeks. Intermediate uveitis is graded by haze; it is done using the photographic scale: grades 0-4 (lower values are a better outcome), utilized by the SUN criteria, based on the Nussenblatt photographic vitreous haze scale |
| Number of Participants With Clinically Significant Improvement of Macular Edema | 12 weeks | Clinically Significant Uveitic Macular Edema: Clinical Improvement of Macular Edema with OCT Documentation of central foveal thickness \< 300 microns |
Countries
United States
Participant flow
Recruitment details
The recruitment period was 06/31/2016 through 08/10/2016 Active follow-up period 06/31/2016 through 12/07/2016 The study was conducted at 1 site Tampa Bay Uveitis Center, LLC 5800 49th Street North, St Petersburg Fl 33709: Outpatient Medical Clinic
Pre-assignment details
The patient after consent was given, were required to have their medical records reviewed and have screening laboratory evaluations
Participants by arm
| Arm | Count |
|---|---|
| H.P. Acthar Subcutaneous Gel Injection For the current protocol we are proposing, 40 U/ml, given twice weekly x 8 weeks, followed by once weekly x 4 weeks: a total 20 doses, using the approved route, with the option to do 4 additional doses if resolution is incomplete.
H.P. ACTHAR SUBCUTANEOUS GEL INJECTION: Subcutaneous injection twice weekly | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
Baseline characteristics
| Characteristic | H.P. Acthar Subcutaneous Gel Injection |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Number of Participants With Clinically Significant Improvement of Macular Edema
Clinically Significant Uveitic Macular Edema: Clinical Improvement of Macular Edema with OCT Documentation of central foveal thickness \< 300 microns
Time frame: 12 weeks
Population: 0
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| H.P. Acthar Subcutaneous Gel Injection | Number of Participants With Clinically Significant Improvement of Macular Edema | Decrease in Central Foveal Thickness <300 | 0 Participants |
| H.P. Acthar Subcutaneous Gel Injection | Number of Participants With Clinically Significant Improvement of Macular Edema | Decrease in central Fovea > 300 Microns | 5 Participants |
Primary
Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography
Subjects will have fundus photography at baseline and 12 weeks. Intermediate uveitis is graded by haze; it is done using the photographic scale: grades 0-4 (lower values are a better outcome), utilized by the SUN criteria, based on the Nussenblatt photographic vitreous haze scale
Time frame: 12 Weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| H.P. Acthar Subcutaneous Gel Injection | Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography | No VH Improvement | 1 Participants |
| H.P. Acthar Subcutaneous Gel Injection | Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography | 1 Step of VH Improvement | 3 Participants |
| H.P. Acthar Subcutaneous Gel Injection | Number of Participants With Photographic Haze Reduced to Grade 0 or Down 2 Steps Documented With Fundus Photography | 2 Step of VH | 1 Participants |