Patients With Newly Diagnosed Active NISUPhase 2USTEKINISUNCT03847272
A Multicenter Phase 2 Single-arm Proof-of-concept Trial to Assess the Efficacy and Safety of Ustekinumab in Association With Prednisone for the Treatment of Non-infectious Severe Uveitis (NISU)
A Phase 2 study testing prednisone and ustekinumab treatment, Ophthalmologic examination and Questionnaires in people with Patients With Newly Diagnosed Active NISU, run by Centre Hospitalier Universitaire Dijon at 2 sites in France.
Trial summary
Uveitis is characterized by inflammation of the uvea, which is the middle portion of the eye. The greatest challenge for the treatment of uveitis is patients who have inflammation involving the posterior segment, either primarily in the vitreous (intermediate uveitis), the choroid or retina (posterior uveitis), or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Newly Diagnosed Active NISU
- What is being tested?
- prednisone and ustekinumab treatment, Ophthalmologic examination and Questionnaires
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesFrance
- Study dates
- 1 Aug 2019to 25 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Patients with newly diagnosed active NISU: evidence of activity within the 3 months prior to the screening visit as per:
- VH (visual haze) ≥ 4 on the Miami 9-step scale (or VH >1+ according to SUN classification)
- and/or macular edema on OCT (Central retinal thickness ≥ 300 microns)
- and/or other signs of intraocular inflammation (e.g. perivascular sheathing of retinal vessels or leakage of retinal vessels on fluorescein angiography (FA)).
- Patients judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening.
- For men and women of childbearing age, effective contraception must be used by the patient and/or his/her partner throughout the duration of treatment with ustekinumab and until 23 weeks after the end of treatment. Breastfeeding is allowed 23 weeks after the end of treatment. Women considered without risk of pregnancy are those with :
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- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system ( IUS)
- bilateral tubal occlusion
- vasectomised partner
- sexual abstinence
- or those surgically sterile (bilateral oophorectomy or hysterectomy).
- or at least one year of menopause (amenorrhea for at least 12 months)
- Patients over 18 years of age
- Affiliation to a the French health insurance system
- Patients who have given their consent
Who cannot join
- Surgery scheduled within 12 months
- Patients with dementia
- Non-compliant patients
- Weight <45 kg or > 100 kg
- Patients under ward of court, tutelage or legal guardianship
- Pregnant or breast-feeding women
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- Infectious uveitis, masquerade syndromes, or uveitis due to causes other than non-infectious uveitis disease (idiopathic uveitis is permitted)
- Isolated anterior uveitis
- Presence of cataract or posterior capsular opacification so severe that an assessment of the posterior segment of either eye is inadequate or impossible
- Contraindication to mydriasis in either eye or presence of posterior synechiae in the study eye such that mydriasis is inadequate for posterior segment examination
- Intraocular pressure ≥ 25mmHg by Goldmann tonometry or advanced glaucoma (e.g., cup-to-disc ratio > 0.9, split fixation on visual field, or need for > 3 intraocular pressure lowering medications to keep IOP < 22 mmHg) in either eye
- Monocular patient
- Sarcoidosis-related uveitis
- History of congenital or acquired immunodeficiency (e.g. common variable immunodeficiency disease).
- History of prior treatment with ustekinumab
- Hypersensitivity to ustekinumab, one of its excipients or another human or murine monoclonal antibody or latex
- Evidence of active infection at the time of baseline visit, or other Infectious contraindication to ustekinumab
- Neoplasia < 5 years, (except for in situ cervical cancer and skin carcinoma with R0 resection)
- Active tuberculosis or sign of latent tuberculosis (based on a history of untreated contact, a history of opacity of more than 1 cm in diameter on the chest x-ray, or an in vitro test positive[Quantiferon® or T-spot-TB®]). A history of TB disease or latent TB whose treatment was completed is not an exclusion criteria, regardless the Quantiferon® or T-spot-TB® is positive or not.
- Known positive laboratory test for syphilis serology, HIV antibody, hepatitis B surface antigen or anti-nucleocapsid antibody of hepatitis B virus, and/or hepatitis C antibody.
- History of multiple sclerosis and/or other demyelinating disorders
- Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
- Screening laboratory and other analyses showing any of the following abnormal results:
- AST, ALT > 1.75 × upper limit of the reference range;
- WBC count < 3.0 × 109/L;
- Other treatments:
- Corticosteroids
- History of ≥3 systemic corticosteroid therapies (topical or inhaled treatments allowed) for another disease (e.g. asthma) within the last 6 months before screening visit
- Dexamethasone intravitreal implant less than 6 months prior to study
- Patients receiving (or having stopped for less than 6 months or 5 elimination half-lives) an immunosuppressive or immunomodulatory drug or biotherapy:
- anti TNF-α,
- tocilizumab,
- abatacept,
- anakinra,
- methotrexate,
- azathioprine,
- ciclosporine,
- cyclophosphamide,
- dapsone
- or corticosteroid pulses
- Live vaccine administered within 30 days preceding inclusion
- Hypersensibility to fluorescein and indocyanin green
Trial locations and contacts
2 sites in 1 country.
About this study
Uveitis is characterized by inflammation of the uvea, which is the middle portion of the eye. The greatest challenge for the treatment of uveitis is patients who have inflammation involving the posterior segment, either primarily in the vitreous (intermediate uveitis), the choroid or retina (posterior uveitis), or involving the entire eye (panuveitis). The term "uveitis" denotes a heterogeneous collection of diseases including infections, systemic immune-mediated diseases like sarcoidosis, and immune-mediated syndromes confined to the eye like sympathetic ophthalmia. Despite the progress in recent decades, uveitis and the related intraocular inflammation are comparable to diabetes or macular degeneration as a cause of lost quality-adjusted life years due to visual morbidity, and as such are a significant public health problem. The Standardization of Uveitis Nomenclature Working Group Guidelines recommend the use of corticosteroids as the first-line therapy for patients with active uveitis. However, long-term corticosteroid treatment can cause serious systemic and ocular side effects, such as hypertension, diabetes, osteoporosis, cataract, and glaucoma that limit its use in the treatment of uveitis. Alternatively, immunomodulatory therapy (IMT) drugs are given as steroid-sparing agents and have shown good clinical results for both systemic diseases and ocular inflammatory diseases. Given the side effects of chronic corticosteroid therapy and better understanding of the mechanisms of autoimmune-mediated uveitis, the aim of the treatment for patients with noninfectious uveitis is steroid-free remission with IMT. While uveitis is a heterogeneous disease with polygenic and environmental factors, most forms of immune-mediated uveitis are thought to be due to an imbalance between regulatory mechanisms that inhibit the immune system and inflammatory mechanisms, which have evolved to rid the body of infectious organisms, but which can result in immune-mediated, often chronic disease if they are activated outside the context of the immediate infection. The pathophysiology of non-infectious uveitis involves the rupture of peripheral tolerance, resulting in auto-aggressive Th1 or Th17 lymphocytes reaching the eye. L-12 and IL-23 are two key cytokines involved in Th1 and Th17 polarization in uveitis, respectively. Furthermore, these two cytokines share a common subunit (p40). Ustekinumab, a humanized anti-p40 monoclonal antibody, is able to target both IL-12 and IL-23 pathways, thus disrupting Th1 and Th17 immune responses.
Decreasing the dose as well as the duration of treatment with GC is of particular importance in uveitis, and ustekinumab, which selectively inhibits Th1 and Th17 pathways in the inflammatory cascade, could provide a ideal additional therapy for non-infectious severe uveitis (NISU) to reach this objective.
Therefore, in the present study, we propose to evaluate the efficacy and safety of ustekinumab for the treatment of NISU.
- Being tested
- prednisone and ustekinumab treatment, Ophthalmologic examination, Questionnaires, Blood samples
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prednisone and ustekinumab treatmentDrug
Treatment with prednisone and ustekinumab (90 mg subcutaneously at inclusion (W0), W4 and W16)
Ophthalmologic examinationOther
Best corrected visual acuity (BCVA) testing, Slit Lamp Exam, tonometry, dilated indirect ophthalmoscopy, optical coherence tomography (OCT), Fluorescein angiography and Indocyanin green angiography
QuestionnairesOther
VFQ-25 and SF-36
Blood samplesBiological
Additional blood samples for immunomonitoring
| Study group | Role | What they receive |
|---|---|---|
| Patients | Experimental | Not described Receives: Drug: prednisone and ustekinumab treatment; Other: Ophthalmologic examination; Other: Questionnaires; Biological: Blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of remission
Measured: Through study completion, an average of 30 months
Percentage of patients free of relapse between week 6 and week 24
Measured: Through study completion, an average of 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2019
- Study start1 Aug 2019
- Primary completion25 Oct 2023
- Study completion25 Oct 2023
Why it stopped: The long inclusion period meant that the question could not be answered within an appropriate timeframe.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With Newly Diagnosed Active NISUStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Dijon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03847272
- Sponsor's protocol ID
- BIELEFELD Janssen-PHRC N 2017
- Acronym
- USTEKINISU
- Status last verified
- Jan 2024
- First submitted
- 15 Feb 2019
- Last updated
- 12 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 2 Single-arm Proof-of-concept Trial to Assess the Efficacy and Safety of Ustekinumab in Association With Prednisone for the Treatment of Non-infectious Severe Uveitis (NISU)
- ClinicalTrials.gov ID
- NCT03847272
- Acronym / sponsor ID
- USTEKINISU / BIELEFELD Janssen-PHRC N 2017
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The long inclusion period meant that the question could not be answered within an appropriate timeframe.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire DijonUniversity, hospital or other
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 25 Oct 2023 (actual)
- Study completion
- 25 Oct 2023 (actual)
- First posted
- 20 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Uveitis is characterized by inflammation of the uvea, which is the middle portion of the eye. The greatest challenge for the treatment of uveitis is patients who have inflammation involving the posterior segment, either primarily in the vitreous (intermediate uveitis), the choroid or retina (posterior uveitis), or involving the entire eye (panuveitis). The term "uveitis" denotes a heterogeneous collection of diseases including infections, systemic immune-mediated diseases like sarcoidosis, and immune-mediated syndromes confined to the eye like sympathetic ophthalmia. Despite the progress in recent decades, uveitis and the related intraocular inflammation are comparable to diabetes or macular degeneration as a cause of lost quality-adjusted life years due to visual morbidity, and as such are a significant public health problem. The Standardization of Uveitis Nomenclature Working Group Guidelines recommend the use of corticosteroids as the first-line therapy for patients with active uveitis. However, long-term corticosteroid treatment can cause serious systemic and ocular side effects, such as hypertension, diabetes, osteoporosis, cataract, and glaucoma that limit its use in the treatment of uveitis. Alternatively, immunomodulatory therapy (IMT) drugs are given as steroid-sparing agents and have shown good clinical results for both systemic diseases and ocular inflammatory diseases. Given the side effects of chronic corticosteroid therapy and better understanding of the mechanisms of autoimmune-mediated uveitis, the aim of the treatment for patients with noninfectious uveitis is steroid-free remission with IMT. While uveitis is a heterogeneous disease with polygenic and environmental factors, most forms of immune-mediated uveitis are thought to be due to an imbalance between regulatory mechanisms that inhibit the immune system and inflammatory mechanisms, which have evolved to rid the body of infectious organisms, but which can result in immune-mediated, often chronic disease if they are activated outside the context of the immediate infection. The pathophysiology of non-infectious uveitis involves the rupture of peripheral tolerance, resulting in auto-aggressive Th1 or Th17 lymphocytes reaching the eye. L-12 and IL-23 are two key cytokines involved in Th1 and Th17 polarization in uveitis, respectively. Furthermore, these two cytokines share a common subunit (p40). Ustekinumab, a humanized anti-p40 monoclonal antibody, is able to target both IL-12 and IL-23 pathways, thus disrupting Th1 and Th17 immune responses.
Decreasing the dose as well as the duration of treatment with GC is of particular importance in uveitis, and ustekinumab, which selectively inhibits Th1 and Th17 pathways in the inflammatory cascade, could provide a ideal additional therapy for non-infectious severe uveitis (NISU) to reach this objective.
Therefore, in the present study, we propose to evaluate the efficacy and safety of ustekinumab for the treatment of NISU.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | Experimental | Drug: prednisone and ustekinumab treatment, Other: Ophthalmologic examination, Other: Questionnaires, Biological: Blood samples |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients with newly diagnosed active NISU: evidence of activity within the 3 months prior to the screening visit as per:
- Patients judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening.
- For men and women of childbearing age, effective contraception must be used by the patient and/or his/her partner throughout the duration of treatment with ustekinumab and until 23 weeks after the end of treatment. Breastfeeding is allowed 23 weeks after the end of treatment. Women considered without risk of pregnancy are those with :
- Patients over 18 years of age
- Affiliation to a the French health insurance system
Key exclusion criteria (42 listed)
- Surgery scheduled within 12 months
- Patients with dementia
- Non-compliant patients
- Weight <45 kg or > 100 kg
- Patients under ward of court, tutelage or legal guardianship
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 |
|---|---|---|
| prednisone and ustekinumab treatmentTreatment with prednisone and ustekinumab (90 mg subcutaneously at inclusion (W0), W4 and W16) | Drug | Patients |
| Ophthalmologic examinationBest corrected visual acuity (BCVA) testing, Slit Lamp Exam, tonometry, dilated indirect ophthalmoscopy, optical coherence tomography (OCT), Fluorescein angiography and Indocyanin green angiography | Other | Patients |
| QuestionnairesVFQ-25 and SF-36 | Other | Patients |
| Blood samplesAdditional blood samples for immunomonitoring | Biological | Patients |
Primary outcome
Percentage of remission
Time frame: Through study completion, an average of 30 months
Percentage of patients free of relapse between week 6 and week 24
Time frame: Through study completion, an average of 30 months
Results and safety
The study was stopped early (reason given: The long inclusion period meant that the question could not be answered within an appropriate timeframe.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing prednisone and ustekinumab treatment, Ophthalmologic examination and Questionnaires in people with Patients With Newly Diagnosed Active NISU, run by Centre Hospitalier Universitaire Dijon at 2 sites in France.
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 18 inclusion and 42 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: stopped early, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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?
The study was stopped early (reason given: The long inclusion period meant that the question could not be answered within an appropriate timeframe.). Results are not available in the source record.
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?
Percentage of remission (time frame: Through study completion, an average of 30 months). 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 12 Jan 2024.