Takayasu ArteritisTAKASIMNCT03192878
Infliximab Biosimilar in Takayasu's Arteritis
An observational study of Takayasu Arteritis, run by Ospedale San Raffaele at 1 site in Italy.
Trial summary
Takayasu arteritis (TA) is a chronic inflammatory disease affecting large and medium caliber arteries, particularly the aortic arch and its main branches. Clinical manifestations are caused by the marked thickening of the wall of the involved vessels, resulting in lumen narrowing and ischemia of the tributary… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Takayasu Arteritis
- What is being tested?
- Infliximab
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2017to Jul 2019
- Phase
- Observational
- 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
Study population: We anticipate to include about 30 patients with Takayasu's arteritis (TA). Specifically, the study will include: I) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, not previously treated with infliximab (the naive arm). II) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, already receiving treatment with originator infliximab (the switch arm).
Who may be able to join
- age> 18 years;
- negative pregnancy test;
- use of a reliable contraceptive method by all potentially fertile patients during the study and for the six months following the end of therapy;
- diagnosis of TA according to the Classification criteria of the American College of Rheumatology 1990;
- Multifocal vascular aortic and arterial involvement as evaluated by imaging examinations (angiography / angio-MRI / vascular ecocolordoppler / PET);
- failure to respond to corticosteroid therapy after 6-8 weeks of prednisone therapy at a dose of 1 mg / Kg per day, or impossibility to reduce the dose of prednisone to 0.5 mg / Kg within 3 months of initiation of therapy and to less than 0.2 mg / kg per day within 6 months of initiation of therapy (may also include patients who, despite receiving combination therapy with prednisone and cyclophosphamide, azathioprine, methotrexate, cyclosporin A, mycophenolate mofetil, leflunomide and rapamycin for at least 3 months, could not reduce the prednisone dose to 0.5 mg / Kg per day within 3 months of initiation of therapy, or to less than 0.2 mg / kg per day within 6 months of initiation of therapy);
- ongoing anti-TNF-alpha treatment with originator infliximab (inclusion criterion for the switch arm).
Who cannot join
- history of lymphoproliferative disease or solid neoplasm in the last 5 years, with the exception of successfully treated and completely resolved squamous cell skin carcinoma;
- history of uncontrolled diabetes, unstable cardiac ischaemia, congestive heart failure (NYHA class III and IV), active intestinal inflammatory disease, active peptic ulcer, recent stroke (within 3 months) and any other pathological conditions that, according to the treating physician, could expose the subject to the risk of adverse events;
- serological tests for hepatitis B or C indicating an active infection;
- history of HIV infection;
- chronic infection, or severe infections requiring hospitalization or intravenous antibiotic treatment within 30 days prior to inclusion in the study, or requiring treatment with oral antibiotics within 14 days prior to enrollment;
- ongoing pregnancy or lactation;
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- history of drug or alcohol abuse;
- Previous diagnosis or signs of demyelinating disease of the central nervous system;
- history of active tuberculosis, histoplasmosis or listeriosis;
- previous infection with M. tuberculosis (as documented by chest x-rays and / or positive quantiferon test), in which case patients will only be enrolled after initiating prophylactic therapy according to current guidelines.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Ospedale San Raffaele
Milan, MI, 20132
Elena M Baldissera, MD, +39022643 ext. 7254, baldissera.elena@hsr.it
Giulio Cavalli, MD, +39022643 ext. 4683, cavalli.giulio@hsr.it
About this study
Official title: A Prospective Observational Study of Infliximab Biosimilar in the Treatment of Takayasu's Arteritis Resistant to Corticosteroids and Conventional Immune-suppressive Treatments
Takayasu arteritis (TA) is a chronic inflammatory disease affecting large and medium caliber arteries, particularly the aortic arch and its main branches. Clinical manifestations are caused by the marked thickening of the wall of the involved vessels, resulting in lumen narrowing and ischemia of the tributary districts. Therapy is based on the use of corticosteroids, immunosuppressants, and biologic drugs including infliximab, a monoclonal antibody blocking tissue necrosis factor (TNF)-alpha. Biosimilar infliximab is commercially available and used in the treatment of various immune-mediated conditions. There are currently no data on the efficacy and safety of biosimilar infliximab in the treatment of TA.
The investigators propose this monocentric, observational, prospective, open label study to evaluate the efficacy and safety of biosimilar infliximab in the treatment of 30 patients with TA. Specifically, the study will include: I) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, not previously treated with infliximab; II) TA patients already receiving treatment with originator infliximab.
Read more
Biosimilar infliximab will be administered at dosages usually employed in the treatment of TA. Specifically, patients not previously treated with the originator drug will receive biosimilar infliximab intravenously at a dose of 5 mg/Kg at time 0, at week 2, at week 4; thereafter, treatment will be administered every 4-6 weeks at a dose of 5-10 mg/kg based on clinical judgement. In patients previously treated with the originator drug, biosimilar infliximab will be administered at the same dosages.
To evaluate the efficacy of therapy, changes in clinical manifestations, laboratory examinations, and imaging findings including angio-magnetic resonance imaging (MRI) of thoracic and abdominal vessels and total body PET/CT scan will be evaluate at time 0 as well as 6 and 12 months following treatment initiation. In order to evaluate the safety of the study treatment, the investigators will stringently evaluate possible side effects of treatment, including infusion reactions, changes in laboratory tests, infection, cancer, autoimmune manifestations, neurological and cardiovascular symptoms.
The total duration of follow up for each patient will be 52 weeks from enrolment.
- Conditions
- Takayasu Arteritis
- Being tested
- Infliximab
- Keywords
- infliximab, biosimilars, treatment
- Medical subject headings
- Takayasu Arteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
infliximab biosimilar
| Study group | Role | What they receive |
|---|---|---|
| Naive patients | Patients with corticosteroid- and/or traditional immunosuppressive drug-resistant Takayasu's arteritis with indication of initiating therapy with anti-TNF-alpha Receives: Drug: Infliximab | |
| Switch patients | Patients with Takayasu's arteritis already in therapy with infliximab originator (Remicade) in whom the originator therapy will be replaced with infliximab biosimilar therapy Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with active disease at month 6
Disease will be defined active when new vascular lesion(s) (aneurysms, stenoses or occlusions, new arterial-wall irregularities) will be detected in arteries (aorta, innominate, subclavian, axillary, common and internal carotid, vertebral, superior and inferior mesenteric, renal, common iliac, and celiac axis) by MRI angiography or when increased arterial glucose uptake will be detected by FDG-PET scanning. Disease will also be defined active if at least 2 of the following will be present: 1) new onset of carotodynia or pain over large vessels, 2) transient ischemic episodes not attributable to other factors, 3) new bruit or new asymmetry in pulses or blood pressure determination, 4) ischemic symptoms (including new-onset claudication), and 5) fever in absence of infection
Measured: 6 months of treatment
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at month 12
Measured: 12 months of treatment
Secondary outcomes (7)
Number of patients with active disease at month 12
Disease will be defined active when new vascular lesion(s) (aneurysms, stenoses or occlusions, new arterial-wall irregularities) will be detected in arteries (aorta, innominate, subclavian, axillary, common and internal carotid, vertebral, superior and inferior mesenteric, renal, common iliac, and celiac axis) by MRI angiography or when increased arterial glucose uptake will be detected by FDG-PET scanning. Disease will also be defined active if at least 2 of the following will be present: 1) new onset of carotodynia or pain over large vessels, 2) transient ischemic episodes not attributable to other factors, 3) new bruit or new asymmetry in pulses or blood pressure determination, 4) ischemic symptoms (including new-onset claudication), and 5) fever in absence of infection
Measured: 12 months of treatment
Impact of the treatment on quality of life as assessed by the HAQ questionnaire
We will evaluate the changes from baseline in the HAQ questionnaires at month 6
Measured: 6 months of treatment
Impact of the treatment on quality of life as assessed by the HAQ questionnaire
We will evaluate the changes from baseline in the HAQ questionnaires at month 12
Measured: 12 months of treatment
Impact of the treatment on quality of life as assessed by the SF36 questionnaire
We will evaluate the changes from baseline in the SF36 questionnaire at month 6
Measured: 6 months of treatment
Impact of the treatment on quality of life as assessed by the SF36 questionnaire
We will evaluate the changes from baseline in the SF36 questionnaire at month 12
Measured: 12 months of treatment
Changes in the serum levels of TNF-alpha and anti-infliximab antibodies before and upon treatment with biosimilar infliximab.
Levels of TNF-alpha and anti-infliximab antibodies will be determined by an immunoenzymatic assay and compared to reference ranges provided by the manufacturer. Serum levels of TNFα are expected to decrease upon treatment with biosimilar infliximab; generation of anti-infliximab antibodies may occur in some patients and may be associated with reduced treatment efficacy.
Measured: 6 months of treatment
Changes in the serum levels of TNF-alpha and anti-infliximab antibodies before and upon treatment with biosimilar infliximab.
Levels of TNF-alpha and anti-infliximab antibodies will be determined by an immunoenzymatic assay and compared to reference ranges provided by the manufacturer. Serum levels of TNFα are expected to decrease upon treatment with biosimilar infliximab; generation of anti-infliximab antibodies may occur in some patients and may be associated with reduced treatment efficacy.
Measured: 12 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start1 Mar 2017
- Primary completionFeb 2019 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Takayasu 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Dagna, Ospedale San Raffaele
- Investigators
- Lorenzo Dagna, MD, Principal investigator, IRCCS H San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03192878
- Sponsor's protocol ID
- TakaSim
- Acronym
- TAKASIM
- Status last verified
- Jun 2017
- First submitted
- 9 May 2017
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Observational Study of Infliximab Biosimilar in the Treatment of Takayasu's Arteritis Resistant to Corticosteroids and Conventional Immune-suppressive Treatments
- ClinicalTrials.gov ID
- NCT03192878
- Acronym / sponsor ID
- TAKASIM / TakaSim
- Conditions
- Takayasu Arteritis
- Keywords
- infliximab, biosimilars, treatment
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Ospedale San RaffaeleUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- Feb 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 20 Jun 2017 (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.
Takayasu arteritis (TA) is a chronic inflammatory disease affecting large and medium caliber arteries, particularly the aortic arch and its main branches. Clinical manifestations are caused by the marked thickening of the wall of the involved vessels, resulting in lumen narrowing and ischemia of the tributary districts. Therapy is based on the use of corticosteroids, immunosuppressants, and biologic drugs including infliximab, a monoclonal antibody blocking tissue necrosis factor (TNF)-alpha. Biosimilar infliximab is commercially available and used in the treatment of various immune-mediated conditions. There are currently no data on the efficacy and safety of biosimilar infliximab in the treatment of TA.
The investigators propose this monocentric, observational, prospective, open label study to evaluate the efficacy and safety of biosimilar infliximab in the treatment of 30 patients with TA. Specifically, the study will include: I) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, not previously treated with infliximab; II) TA patients already receiving treatment with originator infliximab.
Biosimilar infliximab will be administered at dosages usually employed in the treatment of TA. Specifically, patients not previously treated with the originator drug will receive biosimilar infliximab intravenously at a dose of 5 mg/Kg at time 0, at week 2, at week 4; thereafter, treatment will be administered every 4-6 weeks at a dose of 5-10 mg/kg based on clinical judgement. In patients previously treated with the originator drug, biosimilar infliximab will be administered at the same dosages.
To evaluate the efficacy of therapy, changes in clinical manifestations, laboratory examinations, and imaging findings including angio-magnetic resonance imaging (MRI) of thoracic and abdominal vessels and total body PET/CT scan will be evaluate at time 0 as well as 6 and 12 months following treatment initiation. In order to evaluate the safety of the study treatment, the investigators will stringently evaluate possible side effects of treatment, including infusion reactions, changes in laboratory tests, infection, cancer, autoimmune manifestations, neurological and cardiovascular symptoms.
The total duration of follow up for each patient will be 52 weeks from enrolment.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naive patients | – | Drug: InfliximabPatients with corticosteroid- and/or traditional immunosuppressive drug-resistant Takayasu's arteritis with indication of initiating therapy with anti-TNF-alpha |
| Switch patients | – | Drug: InfliximabPatients with Takayasu's arteritis already in therapy with infliximab originator (Remicade) in whom the originator therapy will be replaced with infliximab biosimilar therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We anticipate to include about 30 patients with Takayasu's arteritis (TA). Specifically, the study will include: I) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, not previously treated with infliximab (the naive arm). II) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, already receiving treatment with originator infliximab (the switch arm).
Key inclusion criteria (7 listed)
- age> 18 years;
- negative pregnancy test;
- use of a reliable contraceptive method by all potentially fertile patients during the study and for the six months following the end of therapy;
- diagnosis of TA according to the Classification criteria of the American College of Rheumatology 1990;
- Multifocal vascular aortic and arterial involvement as evaluated by imaging examinations (angiography / angio-MRI / vascular ecocolordoppler / PET);
Key exclusion criteria (10 listed)
- history of lymphoproliferative disease or solid neoplasm in the last 5 years, with the exception of successfully treated and completely resolved squamous cell skin carcinoma;
- history of uncontrolled diabetes, unstable cardiac ischaemia, congestive heart failure (NYHA class III and IV), active intestinal inflammatory disease, active peptic ulcer, recent stroke (within 3 months) and any other pathological conditions that, according to the treating physician, could expose the subject to the risk of adverse events;
- serological tests for hepatitis B or C indicating an active infection;
- history of HIV infection;
- chronic infection, or severe infections requiring hospitalization or intravenous antibiotic treatment within 30 days prior to inclusion in the study, or requiring treatment with oral antibiotics within 14 days prior to enrollment;
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 |
|---|---|---|
| Infliximabinfliximab biosimilar | Drug | Naive patients, Switch patients |
Primary outcome
Number of patients with active disease at month 6
Time frame: 6 months of treatment
Disease will be defined active when new vascular lesion(s) (aneurysms, stenoses or occlusions, new arterial-wall irregularities) will be detected in arteries (aorta, innominate, subclavian, axillary, common and internal carotid, vertebral, superior and inferior mesenteric, renal, common iliac, and celiac axis) by MRI angiography or when increased arterial glucose uptake will be detected by FDG-PET scanning. Disease will also be defined active if at least 2 of the following will be present: 1) new onset of carotodynia or pain over large vessels, 2) transient ischemic episodes not attributable to other factors, 3) new bruit or new asymmetry in pulses or blood pressure determination, 4) ischemic symptoms (including new-onset claudication), and 5) fever in absence of infection
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 12 months of treatment
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at month 12
7 secondary outcomes
Number of patients with active disease at month 12
Time frame: 12 months of treatment
Impact of the treatment on quality of life as assessed by the HAQ questionnaire
Time frame: 6 months of treatment
Impact of the treatment on quality of life as assessed by the HAQ questionnaire
Time frame: 12 months of treatment
Impact of the treatment on quality of life as assessed by the SF36 questionnaire
Time frame: 6 months of treatment
Impact of the treatment on quality of life as assessed by the SF36 questionnaire
Time frame: 12 months of treatment
Changes in the serum levels of TNF-alpha and anti-infliximab antibodies before and upon treatment with biosimilar infliximab.
Time frame: 6 months of treatment
Changes in the serum levels of TNF-alpha and anti-infliximab antibodies before and upon treatment with biosimilar infliximab.
Time frame: 12 months of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Individual participant dataSharing planned: Undecided
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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.
Lorenzo Dagna, MD principal investigator
IRCCS H San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Takayasu Arteritis, run by Ospedale San Raffaele at 1 site in Italy.
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 7 inclusion and 10 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 20 Jun 2017. 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 Italy. 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.
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 Elena M Baldissera, MD (+39022643 ext. 7254, baldissera.elena@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with active disease at month 6 (time frame: 6 months of treatment). 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 20 Jun 2017; AzTrials last refreshed its copy on 2 Nov 2026.