Antisynthetase Syndrome (ASS)Phase 3CATR-PATNCT03770663
Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease
A Phase 3 study testing Cyclophosphamide and azathioprine and Tacrolimus in people with Antisynthetase Syndrome (ASS) and Interstitial Lung Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
"Antisynthetase syndrome (ASS) is one of the most severe inflammatory myopathy (IM), due to pulmonary involvement (interstitial lung disease, ILD). Until now, the most commonly used immunosuppresive therapy in Europe is Cyclophosphamide followed by different immunosuppressive drugs as maintenance therapy, including… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antisynthetase Syndrome (ASS), Interstitial Lung Disease
- What is being tested?
- Cyclophosphamide and azathioprine and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteFrance
- Study dates
- 5 Feb 2021to 2 Jan 2024
- Phase
- Phase 3
- 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
- Age ≥ 18
- Signed informed consent
- Affiliation to the Social security system
- Diagnosis of ASS: positive test for any of the 5 anti-tRNA synthetase antibodies routinely tested (ELISA, Luminex or Linear-dot), including anti-Jo-1, anti-PL7, anti-PL12, anti-EJ and anti-OJ.
- Diagnosis of ILD-related ASS: interstitial lung disease on HRCT.
- Moderate to severe ILD on PFT : FVC < 80% and or cDLCO < 70%
Show all 9Show fewer
- beta-HCG test negative or negative uterine echography (for women of child bearing potential)
- Women of childbearing potential must have an oral contraception (macroprogestatifs) during all the duration of study treatment and 12 months after the last dose of study treatment
- Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of study treatment and 6 months after the last dose of study treatment
Who cannot join
- Pregnancy and/or breast feeding
- Others contraindications to the treatments, including hypersensitivity to the drug (including excipient and active compounds), medical contraception contraindications, severe renal failure, severe hepatic insufficiency and severe psychiatric disorders. Specific contraindications are listed for each experimental medication in Table 6 (according to updated Summary of product characteristics, see Appendix 8)
- Fever or active bacterial infection (ie. septicemia, pneumopathy, pyelonephritis, acute prostatitis …), or parasitic infection (ie. Anguillulosis …),or fungal infection (ie. Invasive pulmonary aspergillosis …), or viral infection (HIV seropositivity, Active Tuberculosis, active B/C viral hepatitis, CMV, active EBV…)
- Active neoplasm
- Previous inefficacy of Cyclophosphamide, Azathioprine or Tacrolimus, not related to adhesion problems.
- Previous use of 3 daily IV steroids < 3 months before patient's enrollment.
Show all 15Show fewer
- ASS-related ILD worsening or relapse under Prednisone > 0.5 mg/kg/day
- Previous use of Cyclophosphamide, Azathioprine or Tacrolimus in the last 6 months.
- Severe ASS requiring ICU (respiratory disease, myocarditis), plasma exchange or IV-Ig.
- Positivity of auto-antibodies associated to Systemic Sclerosis (anti-Telomerase, anti-Centromères, anti-Polymerase III).
- Patients with QTc > 450 msec
- Patients with history of long QT syndrome (including familial) or ventricular arrhythmias
- Concomitant use of drugs prolonging QT / QTc (list of treatments in annex)
- Hypokalemia
- Patients with pulmonary hypertension detected on echocardiography during the screening/selection visit (systolic pulmonary artery pressure (PAP) was 37-50 mmHg, and/or tricuspid regurgitation velocity 2.8-3.4 ms-1) are excluded.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hôpital Universitaire Pitié Salpêtrière
Paris, 75013
Olivier BENVENISTE, MD, olivier.benveniste@aphp.fr
About this study
Official title: Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease : Multicentric Randomized Phase III Trial
"Antisynthetase syndrome (ASS) is one of the most severe inflammatory myopathy (IM), due to pulmonary involvement (interstitial lung disease, ILD). Until now, the most commonly used immunosuppresive therapy in Europe is Cyclophosphamide followed by different immunosuppressive drugs as maintenance therapy, including Azathioprine (and so called " European Strategy "). In the USA however, the first-line immunosuppressive treatment is Tacrolimus (so called " American Strategy "). None of these two different strategies has ever been studied prospectively, and there is no clear comparison of short and long-term treatment efficacy and tolerance. Thus, there are yet no evidences helping the clinicians in the therapeutic management of patients with ASS-related ILD.
The aim of this study is therefore to compare both strategies as first line treatments or in relapsing patients : CATR.PAT study is a 52 weeks, randomized, comparative, controlled, open-labeled, phase III, therapeutic clinical trial, comparing two treatment strategies."
Read the detailed description
"During the study period, according to randomization into two groups (n=38 patients, respectively), patients will receive either:
- Group 1 \& 2 : 3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses of oral Prednisone, started at 1 mg/kg/day from D4 to M12
In association with :
- Group 1 : European Standard of care : 6 IV pulses of Cyclophosphamide (1000 mg) followed from M5 to M12 by oral Azathioprine (2 mg/kg/day), with a maximum of 150 mg/d)
- Group 2 : American Strategy Tacrolimus is given orally from M0 to M12 (started at the initial dose of 2x2mg/d). Tacrolimus doses are regularly adapted to its serum concentration to reach 5-15 ng/ml."
- Being tested
- Cyclophosphamide and azathioprine, Tacrolimus
- Medical subject headings
- Antisynthetase syndrome, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide and azathioprineDrug
European strategy 6 IV pulses of Cyclophosphamide (1000mg) followed from M5 to M12 by oral Azathioprine (2mg/kg/day), with a maximum of 150mg/day
TacrolimusDrug
American strategy Tacrolimus given orally from M0 to M12 (started at the initial dose of 2x2mg/day). Tacrolimus doses are regularly adapted to its serum concentration to reach 5-15ng/mL.
| Study group | Role | What they receive |
|---|---|---|
| European strategy | Experimental | 3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses of oral Prednisone, started at 1 mg/kg/day from D4 to M12
In association with:
6 IV pulses of Cyclophosphamide (1000mg) followed from M5 to M12 by oral Azathioprine (2mg/kg/day), with a maximum of 150mg/day Receives: Drug: Cyclophosphamide and azathioprine |
| American strategy | Experimental | 3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses of oral Prednisone, started at 1 mg/kg/day from D4 to M12
In association with:
Tacrolimus given orally from M0 to M12 (started at the initial dose of 2x2mg/day). Tacrolimus doses are regularly adapted to its serum concentration to reach 5-15ng/mL. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Compare the efficacy of Cyclophosphamide and Azathioprine vs Tacrolimus in patients with ASS related-ILD Time from the initiation of treatment to the first event related to ASS related-ILD (progression free survival)
Measured: From baseline to 12 months
Secondary outcomes (9)
Variation of the six minute walk tests
Compare Global variation of the M0 and M12-six minute walk tests (distance in meter, differential of saturation in %)
Measured: at baseline, 3 months, 6 months, 9 months and 12 months
Forced Vital Capacity (FVC)
Compare Global variation of M0 and M12-FVC (both absolute and %)
Measured: at baseline, 3 months, 6 months, 9 months and 12 months
Diffusing Lung Carbon Monoxyde Capacity (cDLCO)
Compare Global variation of M0 and M12 cDLCO (both absolute and %)
Measured: at baseline, 3 months, 6 months, 9 months and 12 months
Rate of pulmonary improvement
Lung improvement is defined (in the absence of any other pulmonary disease) by 3A. Improvement of at least 20% of the dyspnea visual scale score (1-10) 3B. and/or improvement of pulmonary function tests: increase of the baseline FVC by 10% (% patient predicted value or absolute value) or of the baseline cDLCO by 15% (% patient predicted value or absolute).
3C. and/or improvement of ILD on HRCT-scan (-5% involvement of the lung parenchyma evaluated by the extension score and -10% of the coarseness score of fibrosis): see Appendix 3' 3D. and/or improvement of PaO2 > 10 mmHg (FiO2=21%), without hyperventilation at any test
Measured: at baseline, 3 months, 6 months, 9 months and 12 months
Time to extra-pulmonary improvement
Evaluated as follow :
4A. improvement of the muscle involvement assessed by muscle manual testing (MMT/150, see Appendix 5) at each visit, is defined by an increased score > 20% 4B. biological improvement of the muscle involvement, assessed by creatine kinase levels performed at every visit, is defined by a decreased of baseline creatin kinase > 50% (IU/ml) 4C. improvement of the joint involvement, assessed by the ACR score at every visit is defined by a decrease > 20% of baseline number of swelling and painful joints.
Measured: at each visits
Rate of extra-pulmonary improvement
Extra-pulmonary improvement (muscle and joint involvements) is evaluated as follows :
5A. improvement of the muscle involvement, assessed by MMT/150 muscle testing at baseline and M12, is defined by an increased score > 20% 5B. improvement of the joint involvement, assessed by the ACR score at each visit is define by a decrease > 20% of baseline number of swelling and painful joints.
Measured: at baseline and 12 months
Treatments tolerance
6A. any serious adverse event attributable to any experimental medication, which requires hospitalization, is recorded at any time 6B. side effects are declared by the patients, recorded and reported by the investigators at every visit 6C. the number of patients switching of experimental treatment is recorded 6D. the cumulative dose (mg/kg) of steroids will be compared at the end of the study
Measured: At every visit
Treatment Efficacy
6A. any serious adverse event attributable to any experimental medication, which requires hospitalization, is recorded at any time 6B. side effects are declared by the patients, recorded and reported by the investigators at every visit 6C. the number of patients switching of experimental treatment is recorded 6D. the cumulative dose (mg/kg) of steroids will be compared at the end of the study
Measured: at every visit
Quality of Life with SF-36 scale
Measured: Baseline, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start5 Feb 2021
- Primary completion2 Jan 2024 (estimated)
- Study completion2 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antisynthetase Syndrome (ASS)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03770663
- Sponsor's protocol ID
- P140217
- Other IDs
- 2016-002921-12, 2016
- Acronym
- CATR-PAT
- Status last verified
- Feb 2021
- First submitted
- 7 Dec 2018
- Last updated
- 9 Feb 2021
- 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 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease : Multicentric Randomized Phase III Trial
- ClinicalTrials.gov ID
- NCT03770663
- Acronym / sponsor ID
- CATR-PAT / P140217
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 5 Feb 2021 (actual)
- Primary completion
- 2 Jan 2024 (estimated)
- Study completion
- 2 Jan 2024 (estimated)
- First posted
- 10 Dec 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.
"Antisynthetase syndrome (ASS) is one of the most severe inflammatory myopathy (IM), due to pulmonary involvement (interstitial lung disease, ILD). Until now, the most commonly used immunosuppresive therapy in Europe is Cyclophosphamide followed by different immunosuppressive drugs as maintenance therapy, including Azathioprine (and so called " European Strategy "). In the USA however, the first-line immunosuppressive treatment is Tacrolimus (so called " American Strategy "). None of these two different strategies has ever been studied prospectively, and there is no clear comparison of short and long-term treatment efficacy and tolerance. Thus, there are yet no evidences helping the clinicians in the therapeutic management of patients with ASS-related ILD.
The aim of this study is therefore to compare both strategies as first line treatments or in relapsing patients : CATR.PAT study is a 52 weeks, randomized, comparative, controlled, open-labeled, phase III, therapeutic clinical trial, comparing two treatment strategies."
Detailed description
"During the study period, according to randomization into two groups (n=38 patients, respectively), patients will receive either:
- Group 1 \& 2 : 3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses of oral Prednisone, started at 1 mg/kg/day from D4 to M12
In association with :
- Group 1 : European Standard of care : 6 IV pulses of Cyclophosphamide (1000 mg) followed from M5 to M12 by oral Azathioprine (2 mg/kg/day), with a maximum of 150 mg/d)
- Group 2 : American Strategy Tacrolimus is given orally from M0 to M12 (started at the initial dose of 2x2mg/d). Tacrolimus doses are regularly adapted to its serum concentration to reach 5-15 ng/ml."
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| European strategy | Experimental | Drug: Cyclophosphamide and azathioprine3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses of oral Prednisone, started at 1 mg/kg/day from D4 to M12 In association with: 6 IV pulses of Cyclophosphamide (1000mg) followed from M5 to M12 by oral Azathioprine (2mg/kg/day), with a maximum of 150mg/day |
| American strategy | Experimental | Drug: Tacrolimus3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses of oral Prednisone, started at 1 mg/kg/day from D4 to M12 In association with: Tacrolimus given orally from M0 to M12 (started at the initial dose of 2x2mg/day). Tacrolimus doses are regularly adapted to its serum concentration to reach 5-15ng/mL. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18
- Signed informed consent
- Affiliation to the Social security system
- Diagnosis of ASS: positive test for any of the 5 anti-tRNA synthetase antibodies routinely tested (ELISA, Luminex or Linear-dot), including anti-Jo-1, anti-PL7, anti-PL12, anti-EJ and anti-OJ.
- Diagnosis of ILD-related ASS: interstitial lung disease on HRCT.
Key exclusion criteria (15 listed)
- Pregnancy and/or breast feeding
- Others contraindications to the treatments, including hypersensitivity to the drug (including excipient and active compounds), medical contraception contraindications, severe renal failure, severe hepatic insufficiency and severe psychiatric disorders. Specific contraindications are listed for each experimental medication in Table 6 (according to updated Summary of product characteristics, see Appendix 8)
- Fever or active bacterial infection (ie. septicemia, pneumopathy, pyelonephritis, acute prostatitis …), or parasitic infection (ie. Anguillulosis …),or fungal infection (ie. Invasive pulmonary aspergillosis …), or viral infection (HIV seropositivity, Active Tuberculosis, active B/C viral hepatitis, CMV, active EBV…)
- Active neoplasm
- Previous inefficacy of Cyclophosphamide, Azathioprine or Tacrolimus, not related to adhesion problems.
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 |
|---|---|---|
| Cyclophosphamide and azathioprineEuropean strategy 6 IV pulses of Cyclophosphamide (1000mg) followed from M5 to M12 by oral Azathioprine (2mg/kg/day), with a maximum of 150mg/day | Drug | European strategy |
| TacrolimusAmerican strategy Tacrolimus given orally from M0 to M12 (started at the initial dose of 2x2mg/day). Tacrolimus doses are regularly adapted to its serum concentration to reach 5-15ng/mL. | Drug | American strategy |
Primary outcome
Progression free survival
Time frame: From baseline to 12 months
Compare the efficacy of Cyclophosphamide and Azathioprine vs Tacrolimus in patients with ASS related-ILD Time from the initiation of treatment to the first event related to ASS related-ILD (progression free survival)
9 secondary outcomes
Variation of the six minute walk tests
Time frame: at baseline, 3 months, 6 months, 9 months and 12 months
Forced Vital Capacity (FVC)
Time frame: at baseline, 3 months, 6 months, 9 months and 12 months
Diffusing Lung Carbon Monoxyde Capacity (cDLCO)
Time frame: at baseline, 3 months, 6 months, 9 months and 12 months
Rate of pulmonary improvement
Time frame: at baseline, 3 months, 6 months, 9 months and 12 months
Time to extra-pulmonary improvement
Time frame: at each visits
Rate of extra-pulmonary improvement
Time frame: at baseline and 12 months
Treatments tolerance
Time frame: At every visit
Treatment Efficacy
Time frame: at every visit
Quality of Life with SF-36 scale
Time frame: Baseline, 6 months, 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide and azathioprine and Tacrolimus in people with Antisynthetase Syndrome (ASS) and Interstitial Lung Disease, run by Assistance Publique - Hôpitaux de Paris 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 9 inclusion and 15 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 9 Feb 2021. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Olivier BENVENISTE, MD (+33 (0)1 42 16 10 88, olivier.benveniste@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: From baseline to 12 months). 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 9 Feb 2021.