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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-003254-90 | EudraCT Number |
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This was a multi-center, randomized, active-controlled, open-label study. Approximately 24 patients with active, non-infectious intermediate-, posterior-, or panuveitis requiring systemic immunosuppressive therapy were enrolled.
Safety, efficacy, and PK assessments occurred at scheduled visits over a 12-week period. Low-molecular-weight non-steroidal immunosuppressive medications were allowed up to the baseline day as long as the dose had not changed in the 3 weeks prior to baseline, except for corticosteroid doses for which might have changed.
Patients responding to treatment were offered up to 6 months of extended treatment. Assessments for safety included laboratory safety tests, ECGs, physical exams, ocular exams, vital signs and the monitoring of adverse events. Study participation varied from a minimum of 3 months to a maximum of 9 months.
Approximately 24 patients with active non-infectious uveitis, in at least one eye, requiring intensification of systemic immunosuppressive therapy were enrolled and randomized to receive intravitreal LFG316 or conventional therapy (investigator's discretion). Only one eye (the study eye) were treated with LFG316 and the other eye (fellow eye) were treated at the investigator's discretion.Throughout the study, the fellow eye might have been treated as needed; except that certain systemic medications were prohibited. There was 1 screening and 8 scheduled visits over 85 days for a total of 9 site visits for all patients.
At Day 85, patients receiving LFG316 treatment who met the criteria for a 'responder', were offered an additional 6 months of LFG316 treatment on a PRN basis. Additional 3 scheduled visits were attended by LFG316-responder patients during the extension period. However, patients could have unscheduled visits as needed and as determined by the investigator. Safety evaluation and ocular assessments were performed throughout the study duration. Patients in the treatment extension phase, who experienced a flare post their last dose and required treatment, might have received a dose of LFG316. These patients were assessed for a response at their next PRN visit as scheduled by the investigator. Visit frequency was determined by the investigator. If they continued to respond to LFG316 therapy, they might have remained in the PRN treatment arm. They might have received up to 7 additional doses of LFG316 in the PRN period. Throughout the trial LFG316 were not administered more frequently than monthly. Patients in the extension phase, who discontinued treatment prematurely were asked to return approximately 1 month after their last dose. Low molecular weight non-steroidal immunosuppressive medications were allowed up to the baseline day as long as the dose had not changed in the 3 weeks prior to baseline, except for corticosteroid doses which might have changed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LFG316 -Intravitreal Injection | Experimental |
| |
| Conventional Therapy | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LFG316 | Drug | LFG316 administered intravitreally (IVT) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye | Response rate as defined by:
| Day 85 (end of study) |
| Number of Participants With Remission in Study Eye - Treatment Period | Remission (complete response) was defined as any patient who had:
| Day 85 (end of study) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period | Vitreous haze score (based on funduscopic exam): 0, 0.5/Trace, 1+, 2+, 3+, 4+ Vitreous haze score (scale of 0 to 4) with a score of 4 being the most hazed. | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
| Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period |
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Key Inclusion Criteria:
Visual acuity (ETDRS method) of 20 letters (20/400 Snellen equivalent) or better in the study eye.
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Golden | Colorado | 80401 | United States | ||
| Novartis Investigative Site |
Not provided
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Approximately 24 patients were planned to be enrolled. A total of 25 patients were randomized (18 patients in LFG316 group and 7 patients in conventional therapy group).
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| ID | Title | Description |
|---|---|---|
| FG000 | LFG316 | LFG316 administered intravitreally |
| FG001 | Conventional Therapy | Conventional treatment was selected by the investigator |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 28, 2017 | Aug 15, 2018 |
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| Conventional Therapy |
| Drug |
Conventional Therapy administered in accordance with its prescribing info. |
|
Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts under ETDRS conditions. ETDRS best-corrected visual acuity was obtained in each eye separately under certified ETDRS conditions. This assessment was to be performed prior to pupil dilation. The number of letters read correctly (for each eye) was recorded. BCVA is based on the number of letters read correctly. |
| Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
| Number of Patients With Macular Edema in Study Eye - Treatment Period | Macular edema is a sign of uveitis. | Day 85 (end of study) |
| Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period | Chorioretinal lesions is a sign of uveitis. | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
| Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period | anterior chamber cells score (ACCS) with the scores being 0 (≤ 1 cell), 0.5 (1 to 5 aqueous cells), 1 (6 to 15 aqueous cells), 2 (16 to 25 aqueous cells), 3 (26 to 50 aqueous cells), 4 (>50 aqueous cells). | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
| Number of Participants With or Without Anti-LFG316 Antibodies | Blood will be collected at each visit for the profiling of serum drug concentrations. The summary of immunogenicity (IG) by visit . The immunogenicity data (presence/absence of anti-LFG316 antibodies [anti-drug antibodies]). NO: No immunogenicity; YES: Positive immunogenicity. | Throughout the study (treatment and extension period), up to day 271 |
| Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period | Percent change from baseline (using each patient's pre-dose value as baseline) in total C5 concentrations. | Day 2, 15, 29, 43, 57 and, 85 (end of the study) |
| Marietta |
| Georgia |
| 30060 |
| United States |
| Novartis Investigative Site | Cambridge | Massachusetts | 02142 | United States |
| Novartis Investigative Site | Omaha | Nebraska | 68198-5540 | United States |
| Novartis Investigative Site | Teaneck | New Jersey | 07666 | United States |
| Novartis Investigative Site | Houston | Texas | 77030 | United States |
| Novartis Investigative Site | Bristol | BS1 2LX | United Kingdom |
| Novartis Investigative Site | London | EC1V 2PD | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
|
|
| Treatment Extension Period |
|
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Safety analysis set (SAS): All patients who received study drug (LFG316 or conventional treatment) were included in the safety analysis set.
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| ID | Title | Description |
|---|---|---|
| BG000 | LFG316 | LFG316 administered intravitreally |
| BG001 | Conventional Therapy | Conventional treatment was selected by the investigator |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | SAS | Mean | Standard Deviation | Years |
| ||||||||||||||
| Sex: Female, Male | SAS | Count of Participants | Participants |
| |||||||||||||||
| Ethnicity (NIH/OMB) | Safetyanalysis set | Count of Participants | Participants |
| |||||||||||||||
| Race/Ethnicity, Customized | SAS | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye | Response rate as defined by:
| Efficacy 1 analysis set: All patients in the safety analysis set who received any study treatment (LFG316 or conventional treatment) with evaluable efficacy data for at least one efficacy endpoint(s) (ocular assessments) and with no major protocol deviations that had an impact on efficacy data. | Posted | Number | Participants | Day 85 (end of study) |
|
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| |||||||||||||||||||||||||||||
| Primary | Number of Participants With Remission in Study Eye - Treatment Period | Remission (complete response) was defined as any patient who had:
| Efficacy 1 analysis set | Posted | Count of Participants | Participants | Day 85 (end of study) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period | Vitreous haze score (based on funduscopic exam): 0, 0.5/Trace, 1+, 2+, 3+, 4+ Vitreous haze score (scale of 0 to 4) with a score of 4 being the most hazed. | Efficacy 1 analysis set | Posted | Count of Participants | Participants | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period | Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts under ETDRS conditions. ETDRS best-corrected visual acuity was obtained in each eye separately under certified ETDRS conditions. This assessment was to be performed prior to pupil dilation. The number of letters read correctly (for each eye) was recorded. BCVA is based on the number of letters read correctly. | Efficacy 1 analysis set | Posted | Mean | Standard Deviation | letters | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Patients With Macular Edema in Study Eye - Treatment Period | Macular edema is a sign of uveitis. | Efficacy 1 analysis set | Posted | Count of Participants | Participants | Day 85 (end of study) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period | Chorioretinal lesions is a sign of uveitis. | Efficacy 1 analysis set | Posted | Count of Participants | Participants | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period | anterior chamber cells score (ACCS) with the scores being 0 (≤ 1 cell), 0.5 (1 to 5 aqueous cells), 1 (6 to 15 aqueous cells), 2 (16 to 25 aqueous cells), 3 (26 to 50 aqueous cells), 4 (>50 aqueous cells). | Efficacy 1 analysis set | Posted | Count of Participants | Participants | Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study) |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With or Without Anti-LFG316 Antibodies | Blood will be collected at each visit for the profiling of serum drug concentrations. The summary of immunogenicity (IG) by visit . The immunogenicity data (presence/absence of anti-LFG316 antibodies [anti-drug antibodies]). NO: No immunogenicity; YES: Positive immunogenicity. | Pharmacokinetic analysis set: All patients in the safety analysis set with evaluable PK data and with no protocol deviations affecting PK data. | Posted | Count of Participants | Participants | Throughout the study (treatment and extension period), up to day 271 |
|
| ||||||||||||||||||||||||||||||
| Secondary | Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period | Percent change from baseline (using each patient's pre-dose value as baseline) in total C5 concentrations. | Pharmacodynamic (PD) analysis set: All patients in the safety analysis set with EVALUABLE pharmacodynamics (PD) data (Total C5) and with no major protocol deviations that had an impact on PD data were included in the PD analysis set. | Posted | Mean | Standard Deviation | Percent change in C5 | Day 2, 15, 29, 43, 57 and, 85 (end of the study) |
|
|
Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 5 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LFG316 | LF G316 administered intravitreally | 0 | 18 | 1 | 18 | 11 | 18 |
| EG001 | Conventional Therapy | Conventional treatment was selected by the investigator | 0 | 7 | 0 | 7 | 5 | 7 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Retinal detachment | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Retinopathy proliferative | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Mycotic endophthalmitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Conjunctival hyperaemia | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Cystoid macular oedema | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypotony of eye | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Macular fibrosis | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Ocular hypertension | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Giardiasis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Intraocular pressure increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Optic nerve cup/disc ratio increased | Investigations | MedDRA (20.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | +1 862-778-8300 | Novartis.email@novartis.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Sep 7, 2015 | Aug 15, 2018 | Prot_001.pdf |
| ID | Term |
|---|---|
| D015864 | Panuveitis |
| ID | Term |
|---|---|
| D014605 | Uveitis |
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Black |
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| Improvement of VA ≥ 10 letters (N=15,6) |
|
|
| Improvement of ACC score ≥2 steps (N=7, 1) |
|
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| Resolution of chorioretinal lesions (N= 3, 0) |
|
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|
|
|
|
|
|
|
|
| 0.5/Trace |
|
| 1+ |
|
| 2+ |
|
| 3+ |
|
| 4+ |
|
| 0.5/Trace |
|
| 1+ |
|
| 2+ |
|
| 3+ |
|
| 4+ |
|
| 0.5/Trace |
|
| 1+ |
|
| 2+ |
|
| 3+ |
|
| 4+ |
|
| 0.5/Trace |
|
| 1+ |
|
| 2+ |
|
| 3+ |
|
| 4+ |
|
| 0.5/Trace |
|
| 1+ |
|
| 2+ |
|
| 3+ |
|
| 4+ |
|
| 0.5/Trace |
|
| 1+ |
|
| 2+ |
|
| 3+ |
|
| 4+ |
|
| 0.5; 1-5 cells |
|
| 1; 6-15 cells |
|
| 2; 16-25 cells |
|
| 3; 26-50 cells |
|
| 4; >50 cells |
|
| 0.5; 1-5 cells |
|
| 1; 6-15 cells |
|
| 2; 16-25 cells |
|
| 3; 26-50 cells |
|
| 4; >50 cells |
|
| 0.5; 1-5 cells |
|
| 1; 6-15 cells |
|
| 2; 16-25 cells |
|
| 3; 26-50 cells |
|
| 4; >50 cells |
|
| 0.5; 1-5 cells |
|
| 1; 6-15 cells |
|
| 2; 16-25 cells |
|
| 3; 26-50 cells |
|
| 4; >50 cells |
|
| 0.5; 1-5 cells |
|
| 1; 6-15 cells |
|
| 2; 16-25 cells |
|
| 3; 26-50 cells |
|
| 4; >50 cells |
|
| 0.5; 1-5 cells |
|
| 1; 6-15 cells |
|
| 2; 16-25 cells |
|
| 3; 26-50 cells |
|
| 4; >50 cells |
|