Patients Relapsing Refractory Giant Cell ArteritisPhase 2ULTRANCT03711448
Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis
A Phase 2 study testing prednisone treatment, prednisone and ustekinumab treatment and questionnaires in people with Patients Relapsing Refractory Giant Cell Arteritis, run by Centre Hospitalier Universitaire Dijon at 1 site in France.
Trial summary
Giant cell arteritis (GCA) is the most common form of vasculitis after age 50. It is a vasculitis affecting the large vessels, in particular the aorta and its collateral vessels, especially those in the external carotid area. Corticosteroids are the cornerstone of GCA treatment. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Patients Relapsing Refractory Giant Cell Arteritis
- What is being tested?
- prednisone treatment, prednisone and ustekinumab treatment and questionnaires
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteFrance
- Study dates
- 7 Jan 2019to 11 Sep 2024
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written consent
- Patient with GCA, defined by the following criteria (collected at the time of diagnosis of GCA):
- Age ≥ 50 years old
- AND sedimentation rate VS ≥ 50 mm/h or C-reactive protein CRP ≥ 20 mg/L (optional if the temporal artery biopsy (TAB) is positive)
- AND clinical signs of GCA or signs of rhisomelic pseudopolyarthritis (RPP)
- AND positive TAB (granulomatous vasculitis lesions) OR evidence of vasculitis of large vessels (aorta or supra-aortic trunks) by angio-TDM, PET-scanner and/or angio-MRI.
Show all 16Show fewer
- CRP elevation >10 mg/L on at least one occasion during the 6 weeks prior to inclusion
- Relapse treatment initiated less than 6 weeks ago
- Patient with GCA relapse at a dose of prednisone ≤ 20 mg/d and who has received at least 12 consecutive weeks of corticosteroid therapy since the diagnosis of GCA. Relapse is defined as the reappearance of clinical or radiological sign(s) of GCA after a remission phase of at least 1 month AND despite well followed treatment:
- headache (> 1 day, not relieved by paracetamol and not identical to headache that the patient may have had in the past and that is not related to GCA)
- hyperesthesia of the scalp, claudication of the jaws or tongue, anomaly of the temporal artery
- visual signs related to GCA
- signs of RPP
- non-infectious fever of more than one week
- aggravation, recurrence or appearance of signs of vasculitis of large vessels with angioscanner, angio-MRI or PET scanner
- any other sign related to the activity of the GCA as determined by the investigator
Who cannot join
- Person not affiliated to or not benefiting from a health insurance system
- Weight < 40kg or > 100kg (at inclusion)
- Non-compliant patient
- Adult unable to express consent
- Patient with a psychotic state not controlled by treatment
- Person subject to a measure of legal protection (curatorship, guardianship)
Show all 30Show fewer
- Person subject to judicial control
- Women who have not gone through menopause
- Hypersensitivity to ustekinumab, to any of its excipients or to any other murine or human monoclonal antibody
- Latex hypersensitivity (because the packaging of ustekinumab contains latex, which is only present in syringes)
- Relapse with the presence of obvious ophthalmological signs requiring high-dose corticotherapy (1 mg/kg and/or methylprednisolone bolus)
- Surgery scheduled within 12 months (excluding low-risk surgery: endoscopy, bronchoscopy, hysteroscopy, cystoscopy, biopsy or breast surgery, dental care, dental extractions, eye surgery, outpatient surgery, skin surgery)
- Patient with other autoimmune or auto-inflammatory disease (except RPP, autoimmune thyroiditis, Addison's disease, type 1 diabetes, Biermer's disease and presence of autoantibodies without clinical manifestation)
- Neoplasia < 5 years (excluding in situ cervical cancer and skin carcinomas, excluding melanomas, with healthy margin resections [R0]).
- Patient who has received an organ transplant (apart from a corneal transplant)
- Patient who has received an autograft or hematopoietic marrow allograft
- Unstable or poorly controlled disease, acute or chronic, not related to GCA and considered by the investigator as a contraindication to ustekinumab treatment (examples: recurrent infections, ulcers of the lower limbs poorly controlled, unstable ischemic cardiovascular disease, terminal renal failure, liver failure, heart failure ≥ stage III/IV NYHA, diabetes poorly controlled...).
- Other treatments :
- Patient who has received at least 3 systemic corticoid cures for a condition other than GCA within the last 6 months (dermocorticoids and inhaled corticoids are allowed)
- Patient receiving long-term corticosteroid treatment (excluding dermocorticoids and inhaled corticosteroids) for a condition other than GCA
- Patient currently treated or having received, within 4 weeks, cytotoxic, immunosuppressive (except methotrexate and azathioprine which should however be stopped before inclusion), immunomodulatory (except dapsone which should however be stopped before inclusion) or biotherapic treatment.
- Live vaccine injected within 30 days of inclusion
- Infections :
- Chronic (or acute) viral hepatitis B or C
- HIV infection
- Persistent infection or severe infection requiring hospitalization or intravenous antibiotic treatment within 30 days of inclusion (trial antibiotics, regardless of duration and route of administration, are not an exclusion criterion).
- Infection requiring oral antibiotic treatment within 14 days of inclusion (trial antibiotics, regardless of duration and route of administration, are not an exclusion criterion).
- History of histoplasmosis or listeriosis
- Active tuberculosis
- Sign of latent tuberculosis (based on a history of untreated contagion, an opacity greater than 1 cm in diameter on chest X-ray, or a positive in vitro test [QuantiferonR or T-spot-TBR]). A history of tuberculosis disease or latent tuberculosis whose treatment has been completed and which has been properly conducted does not constitute an exclusion criterion, regardless of the outcome of the QuantiferonR or T-spot-TBR.
Trial locations and contacts
1 site in 1 country.
About this study
Giant cell arteritis (GCA) is the most common form of vasculitis after age 50. It is a vasculitis affecting the large vessels, in particular the aorta and its collateral vessels, especially those in the external carotid area.
Corticosteroids are the cornerstone of GCA treatment. They are very effective but are generally continued for 18 to 24 months or more since at least 30% of patients with GCA will relapse during their follow-up. Thus, the vast majority of patients treated for GCA have at least one adverse event from corticosteroid therapy, which is the main source of morbidity in these elderly patients.
Read more
Reducing the use of corticosteroids, especially during relapses, is therefore a major objective to improve the treatment of patients with GCA. Methotrexate, abatacept and tocilizumab have been shown to be effective during GCA. However, the therapeutic effect of the first two is modest. As for tocilizumab, its use has many limitations: suspensive effect, many contraindications and there are no biological parameters available for reliable monitoring of inflammatory syndrome in these patients.
Recent data have shown the major role of T helper (Th) Th1 and Th17 T cells in the pathophysiology of GCA. Th17 lymphocytes are sensitive to corticosteroid therapy but Th1 persists despite treatment and produces interferon-γ which activates macrophages and smooth muscle cells, leading to remodelling of the vascular wall responsible for ischemic GCA manifestations. Joint targeting of Th17 and Th1 responses is therefore necessary to fully treat the vascular inflammation that exists during GCA. Ustekinumab, which is a monoclonal antibody blocking the subunit common to IL-12 and IL-23 (p40), blocks the Th1 and Th17 responses, and could therefore be an excellent treatment for GCA.
This study aims to evaluate the efficacy of ustekinumab for the treatment of GCA relapses.
Very little data is available on the use of ustekinumab during GCA. Recently, 14 patients with refractory GCA, defined as the occurrence of at least 2 relapses and the inability to reduce the prednisone dose below 10 mg/d, received ustekinumab treatment. No patients relapsed during treatment while the median dose of prednisone was reduced from 20 to 5 mg/d.
Ustekinumab has also been used successfully in a patient with refractory GCA. Under treatment, the patient did not have a new relapse and the dose of prednisone was reduced. In addition, there was a major decrease in the percentages of circulating Th1 and Th17 lymphocytes.
However, to date, no controlled studies have been conducted to confirm the efficacy of ustekinumab during GCA relapses.
This guarantees the originality and innovation of this study.
- Being tested
- prednisone treatment, prednisone and ustekinumab treatment, questionnaires, Blood samples
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prednisone treatmentDrug
tapering prednisone regimen
prednisone and ustekinumab treatmentDrug
Treatment with prednisone and ustekinumab (90 mg subcutaneously at inclusion (W0), W4, W16 and W28)
questionnairesOther
HAQ ; SF-36 ; FACIT-fatigue
Blood samplesBiological
Additional blood samples for immunomonitoring
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Not described Receives: Drug: prednisone treatment; Other: questionnaires; Biological: Blood samples |
| Experimental group | Experimental | Not described Receives: Drug: prednisone and ustekinumab treatment; Other: questionnaires; Biological: Blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of living patients who went into remission after inclusion, without a new relapse and without deviation from the prednisone tapering protocol planned in the study.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2018
- Study start7 Jan 2019
- Primary completion11 Sep 2024
- Study completion11 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients Relapsing Refractory Giant Cell ArteritisStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 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
- NCT03711448
- Sponsor's protocol ID
- SAMSON PHRC I 2017
- Acronym
- ULTRA
- Status last verified
- Oct 2024
- First submitted
- 15 Oct 2018
- Last updated
- 4 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis
- ClinicalTrials.gov ID
- NCT03711448
- Acronym / sponsor ID
- ULTRA / SAMSON PHRC I 2017
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire DijonUniversity, hospital or other
- Study start
- 7 Jan 2019 (actual)
- Primary completion
- 11 Sep 2024 (actual)
- Study completion
- 11 Sep 2024 (actual)
- First posted
- 18 Oct 2018 (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.
Giant cell arteritis (GCA) is the most common form of vasculitis after age 50. It is a vasculitis affecting the large vessels, in particular the aorta and its collateral vessels, especially those in the external carotid area.
Corticosteroids are the cornerstone of GCA treatment. They are very effective but are generally continued for 18 to 24 months or more since at least 30% of patients with GCA will relapse during their follow-up. Thus, the vast majority of patients treated for GCA have at least one adverse event from corticosteroid therapy, which is the main source of morbidity in these elderly patients.
Reducing the use of corticosteroids, especially during relapses, is therefore a major objective to improve the treatment of patients with GCA. Methotrexate, abatacept and tocilizumab have been shown to be effective during GCA. However, the therapeutic effect of the first two is modest. As for tocilizumab, its use has many limitations: suspensive effect, many contraindications and there are no biological parameters available for reliable monitoring of inflammatory syndrome in these patients.
Recent data have shown the major role of T helper (Th) Th1 and Th17 T cells in the pathophysiology of GCA. Th17 lymphocytes are sensitive to corticosteroid therapy but Th1 persists despite treatment and produces interferon-γ which activates macrophages and smooth muscle cells, leading to remodelling of the vascular wall responsible for ischemic GCA manifestations. Joint targeting of Th17 and Th1 responses is therefore necessary to fully treat the vascular inflammation that exists during GCA. Ustekinumab, which is a monoclonal antibody blocking the subunit common to IL-12 and IL-23 (p40), blocks the Th1 and Th17 responses, and could therefore be an excellent treatment for GCA.
This study aims to evaluate the efficacy of ustekinumab for the treatment of GCA relapses.
Very little data is available on the use of ustekinumab during GCA. Recently, 14 patients with refractory GCA, defined as the occurrence of at least 2 relapses and the inability to reduce the prednisone dose below 10 mg/d, received ustekinumab treatment. No patients relapsed during treatment while the median dose of prednisone was reduced from 20 to 5 mg/d.
Ustekinumab has also been used successfully in a patient with refractory GCA. Under treatment, the patient did not have a new relapse and the dose of prednisone was reduced. In addition, there was a major decrease in the percentages of circulating Th1 and Th17 lymphocytes.
However, to date, no controlled studies have been conducted to confirm the efficacy of ustekinumab during GCA relapses.
This guarantees the originality and innovation of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: prednisone treatment, Other: questionnaires, Biological: Blood samples |
| Experimental group | Experimental | Drug: prednisone and ustekinumab treatment, Other: questionnaires, Biological: Blood samples |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written consent
- Patient with GCA, defined by the following criteria (collected at the time of diagnosis of GCA):
- CRP elevation >10 mg/L on at least one occasion during the 6 weeks prior to inclusion
- Relapse treatment initiated less than 6 weeks ago
- Patient with GCA relapse at a dose of prednisone ≤ 20 mg/d and who has received at least 12 consecutive weeks of corticosteroid therapy since the diagnosis of GCA. Relapse is defined as the reappearance of clinical or radiological sign(s) of GCA after a remission phase of at least 1 month AND despite well followed treatment:
Key exclusion criteria (30 listed)
- Person not affiliated to or not benefiting from a health insurance system
- Weight < 40kg or > 100kg (at inclusion)
- Non-compliant patient
- Adult unable to express consent
- Patient with a psychotic state not controlled by treatment
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 treatmenttapering prednisone regimen | Drug | Control group |
| prednisone and ustekinumab treatmentTreatment with prednisone and ustekinumab (90 mg subcutaneously at inclusion (W0), W4, W16 and W28) | Drug | Experimental group |
| questionnairesHAQ ; SF-36 ; FACIT-fatigue | Other | Control group, Experimental group |
| Blood samplesAdditional blood samples for immunomonitoring | Biological | Control group, Experimental group |
Primary outcome
Percentage of living patients who went into remission after inclusion, without a new relapse and without deviation from the prednisone tapering protocol planned in the study.
Time frame: Week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2024.
- Individual participant dataSharing planned: No
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.
1 site 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 treatment, prednisone and ustekinumab treatment and questionnaires in people with Patients Relapsing Refractory Giant Cell Arteritis, run by Centre Hospitalier Universitaire Dijon at 1 site 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 16 inclusion and 30 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 4 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 living patients who went into remission after inclusion, without a new relapse and without deviation from the prednisone tapering protocol planned in the study. (time frame: Week 52). 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 4 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.