Non-infectious Intermediate UveitisPhase 2NCT01526889
Safety,Tolerability and Efficacy of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, posterior-or Panuveitis ,
A Phase 2 study testing LFG316 and Conventional Therapy in people with Non-infectious Intermediate Uveitis and Non-infectious Posterior Uveitis, run by Novartis Pharmaceuticals at 8 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-infectious Intermediate Uveitis, Non-infectious Posterior Uveitis, Non-infectious Panuveitis
- What is being tested?
- LFG316 and Conventional Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 20 Dec 2012to 24 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients 18 years or older
- Active NIU, in at least one eye, as defined below, in patients requiring intensification of systemic immunosuppressive therapy;
- Vitreous haze at least 1+ on the scale of Nussenblatt et al 1985,or
- Chorioretinal lesions due to uveitis (chorioretinal lesions due to infectious uveitis excluded)
- Patients with a flare and at the time of the enrollment on systemic corticosteroid or non-steroidal immunosuppressants had their therapy tapered or stopped, respectively, at the time of intravitreal LFG316 administration.
- Visual acuity (ETDRS method) of 20 letters (20/400 Snellen equivalent) or better in the study eye.
- For female patients, must not be pregnant or lactating and must, unless post-menopausal, use effective contraception.
- Ability to provide informed consent and comply with the protocol.
Who cannot join
- Uveitis so severe that, in the investigator's judgment, it was too risky to test an experimental drug
- Any biologic immunosuppressive agent given via intravitreal, intravenous or subcutaneous route within 4-12 months depending on the agent.
- History of infectious uveitis or endophthalmitis in either eye.
- History of retinal detachment
- Any intraocular surgery, intravitreal injection, periocular injection, or laser photocoagulation to the study eye within 90 days prior to dosing.
- In the study eye, cataract expected to interfere with study conduct or require surgery during the study.
- Forms of uveitis that may have spontaneously resolved
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States6 sites
Novartis Investigative Site
Cambridge, Massachusetts, 02142
Novartis Investigative Site
Golden, Colorado, 80401
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Marietta, Georgia, 30060
Novartis Investigative Site
Omaha, Nebraska, 68198-5540
Novartis Investigative Site
Teaneck, New Jersey, 07666
United Kingdom2 sites
Novartis Investigative Site
Bristol, BS1 2LX
Novartis Investigative Site
London, EC1V 2PD
About this study
Official title: A Randomized, Active-controlled, Open-label, Multicenter proof-of Concept Study of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, Posterior-, or Panuveitis Requiring Systemic Immunosuppressive Therapy
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.
Read the detailed description
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.
- Conditions
- Non-infectious Intermediate Uveitis, Non-infectious Posterior Uveitis, Non-infectious Panuveitis
- Being tested
- LFG316, Conventional Therapy
- Keywords
- Non-infectious uveitis, Panuveitis, Visual acuity, Vitreous Haze, Inflammation of the uvea, inflammation of the middle, pigmented vascular structures of the eye, iris, ciliary body, choroid plexus
- Medical subject headings
- Panuveitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LFG316Drug
LFG316 administered intravitreally (IVT)
Conventional Therapy administered in accordance with its prescribing info.
| Study group | Role | What they receive |
|---|---|---|
| LFG316 -Intravitreal Injection | Experimental | Not described Receives: Drug: LFG316 |
| Conventional Therapy | Active comparator | Not described Receives: Drug: Conventional Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye
Response rate as defined by:
- An improvement of 2 or more steps in vitreous haze (scale of 0 to 4), relative to baseline OR
- An improvement of 10 or more letters in visual acuity (VA), relative to baseline OR
- An improvement of 2 or more steps in anterior chamber cells (ACC) score (scale of 0 to 4), relative to baseline OR
- Absence of chorioretinal lesions as determined by the investigator
Measured: 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:
- a vitreous haze score of 0 or 0.5 (scale of 0 to 4) in the study eye, AND
- an anterior chamber cell score of 0 (scale of 0 to 4), AND
- no chorioretinal lesions in the study eye, AND
- was off all immune modulatory therapy (systemic, corticosteroids and topical), AND
- without any worsening of uveitis during the trial.
Measured: Day 85 (end of study)
Secondary outcomes (7)
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.
Measured: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
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.
Measured: 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.
Measured: Day 85 (end of study)
Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period
Chorioretinal lesions is a sign of uveitis.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Day 2, 15, 29, 43, 57 and, 85 (end of the study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2012 (estimated)
- Study start20 Dec 2012
- Primary completion16 Feb 2017
- Study completion24 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-infectious Intermediate UveitisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01526889
- Sponsor's protocol ID
- CLFG316A2204
- Other IDs
- 2011-003254-90
- Status last verified
- Oct 2018
- First submitted
- 1 Feb 2012
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Active-controlled, Open-label, Multicenter proof-of Concept Study of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, Posterior-, or Panuveitis Requiring Systemic Immunosuppressive Therapy
- ClinicalTrials.gov ID
- NCT01526889
- Acronym / sponsor ID
- CLFG316A2204
- Conditions
- Non-infectious Intermediate Uveitis, Non-infectious Posterior Uveitis, Non-infectious Panuveitis
- Keywords
- Non-infectious uveitis, Panuveitis, Visual acuity, Vitreous Haze, Inflammation of the uvea, inflammation of the middle, pigmented vascular structures of the eye, iris, ciliary body, choroid plexus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2012 (actual)
- Primary completion
- 16 Feb 2017 (actual)
- Study completion
- 24 Aug 2017 (actual)
- First posted
- 6 Feb 2012 (estimated)
- Results
- Posted 31 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LFG316 -Intravitreal Injection | Experimental | Drug: LFG316 |
| Conventional Therapy | Active comparator | Drug: Conventional Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients 18 years or older
- Active NIU, in at least one eye, as defined below, in patients requiring intensification of systemic immunosuppressive therapy;
- Vitreous haze at least 1+ on the scale of Nussenblatt et al 1985,or
- Chorioretinal lesions due to uveitis (chorioretinal lesions due to infectious uveitis excluded)
- Patients with a flare and at the time of the enrollment on systemic corticosteroid or non-steroidal immunosuppressants had their therapy tapered or stopped, respectively, at the time of intravitreal LFG316 administration.
Key exclusion criteria (7 listed)
- Uveitis so severe that, in the investigator's judgment, it was too risky to test an experimental drug
- Any biologic immunosuppressive agent given via intravitreal, intravenous or subcutaneous route within 4-12 months depending on the agent.
- History of infectious uveitis or endophthalmitis in either eye.
- History of retinal detachment
- Any intraocular surgery, intravitreal injection, periocular injection, or laser photocoagulation to the study eye within 90 days prior to dosing.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LFG316LFG316 administered intravitreally (IVT) | Drug | LFG316 -Intravitreal Injection |
| Conventional TherapyConventional Therapy administered in accordance with its prescribing info. | Drug | Conventional Therapy |
Primary outcome
Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye
Time frame: Day 85 (end of study)
Response rate as defined by: 1. An improvement of 2 or more steps in vitreous haze (scale of 0 to 4), relative to baseline OR 2. An improvement of 10 or more letters in visual acuity (VA), relative to baseline OR 3. An improvement of 2 or more steps in anterior chamber cells (ACC) score (scale of 0 to 4), relative to baseline OR 4. Absence of chorioretinal lesions as determined by the investigator
Number of Participants With Remission in Study Eye - Treatment Period
Time frame: Day 85 (end of study)
Remission (complete response) was defined as any patient who had: * a vitreous haze score of 0 or 0.5 (scale of 0 to 4) in the study eye, AND * an anterior chamber cell score of 0 (scale of 0 to 4), AND * no chorioretinal lesions in the study eye, AND * was off all immune modulatory therapy (systemic, corticosteroids and topical), AND * without any worsening of uveitis during the trial.
7 secondary outcomes
Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period
Time frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period
Time frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
Number of Patients With Macular Edema in Study Eye - Treatment Period
Time frame: Day 85 (end of study)
Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period
Time frame: 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
Time frame: Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)
Number of Participants With or Without Anti-LFG316 Antibodies
Time frame: Throughout the study (treatment and extension period), up to day 271
Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period
Time frame: Day 2, 15, 29, 43, 57 and, 85 (end of the study)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LFG316 and Conventional Therapy in people with Non-infectious Intermediate Uveitis and Non-infectious Posterior Uveitis, run by Novartis Pharmaceuticals at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye (time frame: Day 85 (end of study)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.