Giant Cell ArteritisPhase 2TOCIAIONNCT04239196
Efficacy of Tocilizumab for the Treatment of Acute AION Related to GCA
A Phase 2 study testing tocilizumab and IV steroids combination and IV steroids combination alone in people with Giant Cell Arteritis and Optic Ischaemic Neuropathy, run by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts at 10 sites in France.
Trial summary
AION is the main cause of blindness in patients with GCA. High dose steroid is the reference treatment of this condition, but medical unmet need remains. Subcutaneous tocilizumab, a targeted biotherapy, recently received marketing authorization for the treatment of GCA, but only demonstrated at yet that it can allow… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Giant Cell Arteritis, Optic Ischaemic Neuropathy
- What is being tested?
- tocilizumab and IV steroids combination and IV steroids combination alone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 10 sitesFrance
- Study dates
- 10 Sep 2020to 10 Dec 2022
- 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
- Age of 50 years or older
- Social insurance
- Diagnosis of AION, characterized by sudden and painless loss of vision, of less than one week, accompanied by pallid swelling of the optic disc
- Sudden permanent visual loss due to AION, of less than one week
- Diagnosis of GCA based on the 1st (age ≥ 50 years) and the 3rd (Diagnosis of AION) criteria and at least one among the following :
- One unequivocal symptom among: New onset localized headache, scalp or temporal artery tenderness, otherwise unexplained mouth or jaw pain under mastication, or unequivocal symptoms of polymyalgia rheumatic (shoulder and/or hip girdle pain associated with inflammatory stiffness).
Show all 9Show fewer
- Elevated erythrocyte sedimentation rate (≥ 50 at 1 hour) or C-reactive protein (≥ 10 mg/l), otherwise unexplained
- Abnormal artery biopsy Biopsy specimen with artery showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells.
- Evidence of large or medium-size vessel vasculitis at ultrasound, magnetic resonance angiography, computed tomography angiography, or positron emission tomography-computed tomography.
Who cannot join
- Other ocular involvements related to GCA (central retinal artery occlusion, posterior ischemic optic neuropathy, transient ocular manifestations, occipital stroke), if not associated with AION
- Biological targeting therapy within 3 months preceding the study
- Evidence of active infection
- History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin or solid tumors treated with curative therapy and disease-free for at least 5 years
- History of recurrent infections, diverticulitis or intestinal ulceration and ASAT/ALAT > 5 * upper limit of normal, according to the Summary of Product Characteristics of tocilizumab
- Contraindication to steroids and/or aspirin administrated in the treatment
Show all 16Show fewer
- Breastfeeding women and women with childbearing potential without highly effective contraception.
- Pregnant or nursing (lactating) women confirmed by a positive βHCG laboratory test at the inclusion
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and for 3 months after the last administration of tocilizumab.
- Cytopenia, as defined by platelet count < 100 × 109/L (100,000/mm3), hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L), absolute neutrophil count < 2.0 × 109/L (2000/mm3), absolute lymphocyte count < 0.5 × 109/L (500/mm3)
- Insufficient liver function (Child Pugh C )
- Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or creatinine clearance of 20 ml/min or less
- Patients with previously untreated tuberculosis, previously known TDM/radiographic evidence suggestive of active and/or sequellar tuberculosis
- HIV infected, hepatitis C infected, or a positive hepatitis B surface antigen if known before study inclusion
- Contraindication to and precaution in use of tocilizumab according to the summary product description
- Inability to provide informed consent
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites, 5 recruiting
- Active, not recruiting
CHU de Caen - Hôpital de la Côte de Nacre
Caen, 14033
- Recruiting
Hôpital François Mitterrand
Dijon, 21000
Maxime Samson, 03 80 29 34 32, maxime.samson@chu-dijon.fr
- Active, not recruiting
CHU de Limoges
Limoges, 87042
- Active, not recruiting
CH Montfermeil
Montfermeil, 93370
- Recruiting
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Paris, 75012
Emmanuel Heron, MD, 0140021604, eheron@15-20.fr
- Recruiting
Saint-Antoine Hospital
Paris, 75012
Arsene Mekinian, MD, 0149282104 ext. +33, arsene.mekinian@aphp.fr
- Active, not recruiting
Pitié-Salpetrière Hospital
Paris, 75013
- Recruiting
Cochin Hospital
Paris, 75014
Benjamin terrier, MD, PHD, 01 58 41 14 61, benjamin.terrier@aphp.fr
- Recruiting
Fondation Rothschild,
Paris, 75019
Catherine Vignal, 0148036881, cvignal@for.paris
- Active, not recruiting
Groupe Hospitalier Diaconesses-Croix Saint Simon,
Paris, 75020
About this study
Official title: Open Label Phase II Randomized Non-comparative Study of SC Tocilizumab Associated With IV Pulse Steroid Versus IV Pulse Steroid Alone for the Treatment of Acute Anterior Ischemic Optic Neuropathy Associated With Giant Cell Arteritis
AION is the main cause of blindness in patients with GCA. High dose steroid is the reference treatment of this condition, but medical unmet need remains. Subcutaneous tocilizumab, a targeted biotherapy, recently received marketing authorization for the treatment of GCA, but only demonstrated at yet that it can allow steroid dose sparing. The aim of this study is to assess the benefit of tocilizumab and IV steroids combination or IV steroids alone, in the treatment of AION due to GCA.
Read the detailed description
Tocilizumab will be proposed to eligible patients as an emergency treatment, in addition to the standard high-dose steroid treatment. Each patient will receive the reference treatment, i.e. one pulse of high dose intravenous methylprednisolone per day during 3 days, followed by 1 mg/kg/day oral prednisone, and low dose aspirin. Depending on the randomization, each patient will receive the reference treatment only, or will received in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week), the first tocilizumab injection being delivered on the same day than the first steroid IV pulse. Study visits will take place at 4, 8 and 13 weeks. The primary endpoint will be the ocular improvement at W8, defined as an increase of at least two lines of visual acuity on the ETRS chart. For each patient, the duration of participation will by of 3 months. The study duration is expected to be 15 months.
- Conditions
- Giant Cell Arteritis, Optic Ischaemic Neuropathy
- Being tested
- tocilizumab and IV steroids combination, IV steroids combination alone
- Medical subject headings
- Giant Cell Arteritis, Optic Neuropathy, Ischemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tocilizumab and IV steroids combinationDrug
Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months.
Patients will receive in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week).
IV steroids combination aloneOther
Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months.
| Study group | Role | What they receive |
|---|---|---|
| tocilizumab and IV steroids combination | Experimental | Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. Patients will receive in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week). Receives: Drug: tocilizumab and IV steroids combination |
| IV steroids combination alone | Other | Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. Receives: Other: IV steroids combination alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
ocular change
The primary endpoint will be the ocular change at Week 8. This change will be defined as the increase of at least two lines of visual acuity on the ETDRS chart.
Measured: Week 8
Secondary outcomes (10)
Decrease of vision
Stabilization of vision, as judged at Week 8 after treatment start, correspond to a lack of deterioration :
- If the patient can see the light initially, no light perception at W8 will represent a deterioration
- If the patient is able to count finger at any distance, but the visual acuity is less than 20/400 on the ETRS chart, a "off chart" visual acuity at W8 will represent a deterioration
- If initial visual acuity is equal or more than 20/400, a loss of 2 lines or more on the ETDRS at Week 8 will represent deterioration
Measured: Week 8
Occurrence of a visual improvement
Occurrence of a visual improvement defined as an increase of two lines or more of visual acuity on ETDRS chart, a clinically significant difference, at Week 4 and Week 13
Measured: Week 4 and Week 13
Change in Mean Deviation
Change in Mean Deviation (MD) measured on an automatized Visual Field (SITA Standard Humphrey 24-2) at weeks 4, 8, and 13
Measured: weeks 4, 8, and 13
Changes in angio-OCT
Changes in angio-OCT between baseline and Week 4 : superficial and deep vascular plexus will be examined to look for the decrease of ischemia in peripapillary and macular areas.
Measured: Week 0 and Week 4
improvement of other manifestations of GCA
Proportion of patients with improvement of other manifestations of GCA with tocilizumab and prednisone at weeks 4, 8, and 13
Measured: weeks 4, 8, and 13
biological improvement
Proportion of patients with biological improvement (i.e. CRP and ESR) with tocilizumab and prednisone at weeks 4, 8, and 13
Measured: weeks 4, 8, and 13
recurrence of AION
Influence of 1-month tocilizumab treatment on recurrence of AION, at W13.
Measured: week 13
recurrence of GCA
Influence of 1-month tocilizumab treatment on recurrence of GCA, at Week 13.
Measured: Week 13
first recurrence of GCA
Time to first recurrence of GCA
Measured: weeks 1, 2, 3, 4, 8 and 13
Immunological biomarkers
Immunological biomarkers of response to Tocilizumab assessed at W0, W4, and W13.
Measured: weeks 0,4 and 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start10 Sep 2020
- Primary completion9 Nov 2020
- Study completion10 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Model description
- optimal Simon two-stage design
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Chugai
- Responsible party
- Sponsor
- Investigators
- Emmanuel Heron, MD, Principal investigator, Centre Hospitalier National d'Ophtalmologie des Quinze-Vints
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04239196
- Sponsor's protocol ID
- P17-03
- Other IDs
- 2019-001145-40, 2019
- Acronym
- TOCIAION
- Status last verified
- Mar 2022
- First submitted
- 19 Nov 2019
- Last updated
- 18 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Phase II Randomized Non-comparative Study of SC Tocilizumab Associated With IV Pulse Steroid Versus IV Pulse Steroid Alone for the Treatment of Acute Anterior Ischemic Optic Neuropathy Associated With Giant Cell Arteritis
- ClinicalTrials.gov ID
- NCT04239196
- Acronym / sponsor ID
- TOCIAION / P17-03
- Conditions
- Giant Cell Arteritis, Optic Ischaemic Neuropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Centre Hospitalier National d'Ophtalmologie des Quinze-VingtsUniversity, hospital or other
- Collaborators
- Roche Chugai
- Study start
- 10 Sep 2020 (actual)
- Primary completion
- 9 Nov 2020 (actual)
- Study completion
- 10 Dec 2022 (estimated)
- First posted
- 23 Jan 2020 (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.
AION is the main cause of blindness in patients with GCA. High dose steroid is the reference treatment of this condition, but medical unmet need remains. Subcutaneous tocilizumab, a targeted biotherapy, recently received marketing authorization for the treatment of GCA, but only demonstrated at yet that it can allow steroid dose sparing. The aim of this study is to assess the benefit of tocilizumab and IV steroids combination or IV steroids alone, in the treatment of AION due to GCA.
Detailed description
Tocilizumab will be proposed to eligible patients as an emergency treatment, in addition to the standard high-dose steroid treatment. Each patient will receive the reference treatment, i.e. one pulse of high dose intravenous methylprednisolone per day during 3 days, followed by 1 mg/kg/day oral prednisone, and low dose aspirin. Depending on the randomization, each patient will receive the reference treatment only, or will received in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week), the first tocilizumab injection being delivered on the same day than the first steroid IV pulse. Study visits will take place at 4, 8 and 13 weeks. The primary endpoint will be the ocular improvement at W8, defined as an increase of at least two lines of visual acuity on the ETRS chart. For each patient, the duration of participation will by of 3 months. The study duration is expected to be 15 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- optimal Simon two-stage design
| Arm | Type | Receives |
|---|---|---|
| tocilizumab and IV steroids combination | Experimental | Drug: tocilizumab and IV steroids combinationEvery patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. Patients will receive in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week). |
| IV steroids combination alone | Other | Other: IV steroids combination aloneEvery patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age of 50 years or older
- Social insurance
- Diagnosis of AION, characterized by sudden and painless loss of vision, of less than one week, accompanied by pallid swelling of the optic disc
- Sudden permanent visual loss due to AION, of less than one week
- Diagnosis of GCA based on the 1st (age ≥ 50 years) and the 3rd (Diagnosis of AION) criteria and at least one among the following :
Key exclusion criteria (16 listed)
- Other ocular involvements related to GCA (central retinal artery occlusion, posterior ischemic optic neuropathy, transient ocular manifestations, occipital stroke), if not associated with AION
- Biological targeting therapy within 3 months preceding the study
- Evidence of active infection
- History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin or solid tumors treated with curative therapy and disease-free for at least 5 years
- History of recurrent infections, diverticulitis or intestinal ulceration and ASAT/ALAT > 5 * upper limit of normal, according to the Summary of Product Characteristics of tocilizumab
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 |
|---|---|---|
| tocilizumab and IV steroids combinationEvery patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. Patients will receive in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week). | Drug | tocilizumab and IV steroids combination |
| IV steroids combination aloneEvery patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. | Other | IV steroids combination alone |
Primary outcome
ocular change
Time frame: Week 8
The primary endpoint will be the ocular change at Week 8. This change will be defined as the increase of at least two lines of visual acuity on the ETDRS chart.
10 secondary outcomes
Decrease of vision
Time frame: Week 8
Occurrence of a visual improvement
Time frame: Week 4 and Week 13
Change in Mean Deviation
Time frame: weeks 4, 8, and 13
Changes in angio-OCT
Time frame: Week 0 and Week 4
improvement of other manifestations of GCA
Time frame: weeks 4, 8, and 13
biological improvement
Time frame: weeks 4, 8, and 13
recurrence of AION
Time frame: week 13
recurrence of GCA
Time frame: Week 13
first recurrence of GCA
Time frame: weeks 1, 2, 3, 4, 8 and 13
Immunological biomarkers
Time frame: weeks 0,4 and 13
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2022.
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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.
Emmanuel Heron, MD principal investigator
Centre Hospitalier National d'Ophtalmologie des Quinze-Vints
10 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 tocilizumab and IV steroids combination and IV steroids combination alone in people with Giant Cell Arteritis and Optic Ischaemic Neuropathy, run by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts at 10 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 9 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 18 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tania RILCY (+33 140021126, trilcy@15-20.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ocular change (time frame: Week 8). 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 18 Mar 2022.