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Study of Salvage Therapy to Treat Patients With Granulomatosis With Polyangiitis (SATELITE)

Primary Purpose

Granulomatosis With Polyangiitis, Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Status

Not yet recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Rituximab

Tocilizumab

Abatacept

About this trial

This is an interventional treatment trial for Granulomatosis With Polyangiitis focused on measuring Granulomatosis with Polyangiitis, Anti-neutrophil cytoplasmic antibody, Salvage therapy, Standard of care therapy, Inadequate response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Newly diagnosed or relapsing granulomatosis with polyangiitis according to American College of Rheumatology criteria, EMA classification algorithm and/or the 2012 revised Chapel Hill Consensus Conference definition.
Aged 18 years or older
Active clinical manifestations attributable to GPA
An inadequate response to previous standard of care therapy including
1. Both a combination of glucocorticoids plus cyclophosphamide and a combination of glucocorticoids plus rituximab
2. Or an inadequate response to a combination of glucocorticoids plus rituximab and a contraindication to cyclophosphamide
An inadequate response to treatment defined as follows:
1. A progressive disease unresponsive to previous standard of care therapy after 12 weeks of treatment
2. Or a lack of response, defined as < 50% reduction in the disease activity score, after 12 weeks of treatment
3. Or a persistent active disease attributable to either a vasculitic or a granulomatous manifestation of GPA that requires the maintenance of corticosteroids ≥ 7.5 mg/day of equivalent prednisone after ≥ 12 weeks of treatment.
A stable dose of oral glucocorticoids of ≥ 7.5 mg/day of equivalent prednisone within the 4 weeks before enrollment. Pulses of methylprednisolone (1 to 3 pulses of 7.5 to 15 mg/kg each; ≤ 1000 mg) are allowed if necessary, according to severity before starting the experimental treatment.
A stable dose of conventional disease-modifying anti-rheumatic drugs (cDMARD) within 4 weeks before enrollment if the patient is currently treated with a cDMARD
Patients must have the ability to understand the requirements of the study, provide written informed consent prior to participation in the study (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)
Patients must have an affiliation with a mode of social security (profit or being entitled)

Exclusion Criteria:

An allergy or hypersensitivity to monoclonal antibodies or either of the study drugs (rituximab, abatacept or tocilizumab) or to their excipients
A previous treatment with a combination of rituximab plus a cDMARD, with abatacept, or with tocilizumab
A contraindication to a combination of rituximab plus a cDMARD, to abatacept, or to tocilizumab (including an ongoing infection; history of recent cancer <5 years before enrollment, except for cured non-melanoma skin cancer); pregnancy; and breastfeeding.
Patients with severe vasculitis manifestations that requires plasma exchange therapy including severe renal failure with a creatinine level ≥350 µmol/L or severe alveolar haemorrhage
Patients with vasculitis in remission
Patients with symptoms attributable to chronic and non-active GPA
Patients with severe cardiac failure defined as class IV in New York Heart Association
Patients with acute infections or chronic active infections (including HIV, HBV or HCV)
Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment
Pregnant women and lactation. All women with childbearing potential are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception from the date of consent through the end of the study, and for women who are taking abatacept through 14 weeks after the last treatment administration, for women who are taking tocilizumab through 3 months after the last treatment administration, for women who are taking rituximab in combination with methotrexate through 6 months after the last treatment administration, for women who are taking rituximab in combination with mycofenolate mofetil or with azathioprine through 3 months after the last treatment administration
Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol
Patients included in other investigational therapeutic study within the previous 3 months
Patients suspected not to be observant to the proposed treatments
Laboratory parameter exclusions
1. aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) > 5 times upper limit of normal
2. Platelet count <100.000/mm3
3. White blood cell count <2000/mm3

Sites / Locations

Hôpital de la Croix Saint Simon

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Rituximab + cDMARD

Tocilizumab

Abatacept

Arm Description

Rituximab will be administered at 375 mg/m²/week for four consecutive weeks. Maintenance rituximab at a fixed dose of 500 mg will be administered at week 24 and at week 52. The choice of the cDMARD will be left to the treating clinician and will include either methotrexate, azathioprine or mycophenolate mofetil, but the choice will be preferably methotrexate. Methotrexate will be administered orally or subcutaneously at 0.3 mg/kg/week, azathioprine orally at 2-3 mg/kg/d and mycophenolate mofetil orally at 2-3 g/d.

Tocilizumab will be administered subcutaneously every week at a fixed dose of 162 mg per week.

Abatacept will be administered subcutaneously every week at a fixed dose of 125 mg per week.

Outcomes

Primary Outcome Measures

Proportion of patients with a response or a remission

defined according to the EULAR recommendations. Remission is defined as the absence of disease activity attributable to active disease qualified by the need for ongoing stable maintenance immunosuppressive therapy. The term ''active disease'' is not restricted to vasculitis only, but also includes other inflammatory features like granulomatous inflammation. Response is defined as a 50% reduction of disease activity score and absence of new manifestations.

Secondary Outcome Measures

Proportion of patients with a response or a remission at week 26 and 52.

according to the EULAR recommendations

Physician's and patient's global assessment of disease activity

The difference between the physician's and patient's global assessment of disease activity between baseline and week 12 and between baseline and week 52 using a scale ranging from 0 to 100, with higher scores indicating more activity.

Patient-reported outcomes

The patient-reported outcomes (PRO) including the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire, a 29-item profile measure comprising six domains, with higher scores meaning more active disease, at week 12, 24, and 52 after randomization, and during the long-term follow-up.

Adverse events

The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at week 26 and 52 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions

Corticosteroids use

The area under the curve for corticosteroids at week 26 and 52

Vasculitis Damage Index

The Vasculitis Damage Index (VDI, scoring from 0 to 58, higher scores indicating more damage) at week 26 and 52

Health Assessment Questionnaire (HAQ)

ranging from 0 to 3, with higher scores indicating worse functional impairment

Short Form 36 (SF-36) Health questionnaire

scores range from 0 to 100 for each component, with lower scores indicating greater impairment of quality of life

ANCA titers

Evolution of ANCA titers in the treatment groups

Full Information

NCT ID

NCT04871191

First Posted

February 26, 2021

Last Updated

February 6, 2023

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

1. Study Identification

Unique Protocol Identification Number

NCT04871191

Brief Title

Study of Salvage Therapy to Treat Patients With Granulomatosis With Polyangiitis

Acronym

SATELITE

Official Title

Salvage Therapy for Patients With Inadequate Response to Standard of Care Therapy in Granulomatosis With Polyangiitis

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

March 2023 (Anticipated)

Primary Completion Date

September 2026 (Anticipated)

Study Completion Date

January 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to identify the most promising therapeutic strategy for patients with granulomatosis with polyangiitis and inadequate response to standard of care therapy. It will evaluate the efficacy to induce remission of three different salvage strategies including: a combination of rituximab with addition of a conventional disease-modifying antirheumatic drugs (either methotrexate, azathioprine or mycophenolate mofetil, but preferentially methotrexate); tocilizumab; or abatacept.

Detailed Description

Granulomatosis with polyangiitis (GPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Combination of glucocorticoids and either cyclophosphamide or rituximab is the standard of care for remission-induction of new-onset organ-threatening or life-threatening GPA. Few patients fail to respond to both cyclophosphamide and rituximab, but it is not uncommon for patients to have persistent disease activity resulting in inability to taper glucocorticoids, which is also considered refractory disease. The current recommendations for patients with GPA refractory to remission-induction therapy are to switch from cyclophosphamide to rituximab or from rituximab to cyclophosphamide. However, there are no recommendations for the management of patients with inadequate response after both treatments. Treatment with a biologic disease-modifying antirheumatic drugs (DMARD) or a combination of rituximab and a cDMARD are potential treatments options but have not been properly evaluated in such cases. Among biologic DMARD that have been evaluated in AAV, some have shown promising results, including tocilizumab and abatacept. Identifying the most promising therapeutic strategy for patients with GPA and inadequate response to standard of care therapy may improve management of GPA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Granulomatosis With Polyangiitis, Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Keywords

Granulomatosis with Polyangiitis, Anti-neutrophil cytoplasmic antibody, Salvage therapy, Standard of care therapy, Inadequate response

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Rituximab + cDMARD

Arm Type

Active Comparator

Arm Description

Arm Title

Tocilizumab

Arm Type

Experimental

Arm Description

Tocilizumab will be administered subcutaneously every week at a fixed dose of 162 mg per week.

Arm Title

Abatacept

Arm Type

Experimental

Arm Description

Abatacept will be administered subcutaneously every week at a fixed dose of 125 mg per week.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Mabthera

Intervention Description

375 mg/m²/week for four consecutive weeks (Week 0, 1, 2 and 3) Maintenance rituximab at a fixed dose of 500 mg will be administered at week 24 and at week 52.

Intervention Type

Drug

Intervention Name(s)

Tocilizumab

Other Intervention Name(s)

RoActemra

Intervention Description

Subcutaneous injection of 162 mg per week

Intervention Type

Drug

Intervention Name(s)

Abatacept

Other Intervention Name(s)

Orencia

Intervention Description

Subcutaneous injection of 125 mg per week

Primary Outcome Measure Information:

Title

Proportion of patients with a response or a remission

Description

Time Frame

week 12

Secondary Outcome Measure Information:

Title

Proportion of patients with a response or a remission at week 26 and 52.

Description

according to the EULAR recommendations

Time Frame

week 26 and 52

Title

Physician's and patient's global assessment of disease activity

Description

Time Frame

week 12 and 52

Title

Patient-reported outcomes

Description

Time Frame

week 12, 24 and 52

Title

Adverse events

Description

Time Frame

week 26 and 52

Title

Corticosteroids use

Description

The area under the curve for corticosteroids at week 26 and 52

Time Frame

week 26 and 52

Title

Vasculitis Damage Index

Description

The Vasculitis Damage Index (VDI, scoring from 0 to 58, higher scores indicating more damage) at week 26 and 52

Time Frame

week 26 and 52

Title

Health Assessment Questionnaire (HAQ)

Description

ranging from 0 to 3, with higher scores indicating worse functional impairment

Time Frame

week 26 and 52

Title

Short Form 36 (SF-36) Health questionnaire

Description

scores range from 0 to 100 for each component, with lower scores indicating greater impairment of quality of life

Time Frame

week 26 and 52

Title

ANCA titers

Description

Evolution of ANCA titers in the treatment groups

Time Frame

week 26 and 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Newly diagnosed or relapsing granulomatosis with polyangiitis according to American College of Rheumatology criteria, EMA classification algorithm and/or the 2012 revised Chapel Hill Consensus Conference definition. Aged 18 years or older Active clinical manifestations attributable to GPA An inadequate response to previous standard of care therapy including Both a combination of glucocorticoids plus cyclophosphamide and a combination of glucocorticoids plus rituximab Or an inadequate response to a combination of glucocorticoids plus rituximab and a contraindication to cyclophosphamide An inadequate response to treatment defined as follows: A progressive disease unresponsive to previous standard of care therapy after 12 weeks of treatment Or a lack of response, defined as < 50% reduction in the disease activity score, after 12 weeks of treatment Or a persistent active disease attributable to either a vasculitic or a granulomatous manifestation of GPA that requires the maintenance of corticosteroids ≥ 7.5 mg/day of equivalent prednisone after ≥ 12 weeks of treatment. A stable dose of oral glucocorticoids of ≥ 7.5 mg/day of equivalent prednisone within the 4 weeks before enrollment. Pulses of methylprednisolone (1 to 3 pulses of 7.5 to 15 mg/kg each; ≤ 1000 mg) are allowed if necessary, according to severity before starting the experimental treatment. A stable dose of conventional disease-modifying anti-rheumatic drugs (cDMARD) within 4 weeks before enrollment if the patient is currently treated with a cDMARD Patients must have the ability to understand the requirements of the study, provide written informed consent prior to participation in the study (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits) Patients must have an affiliation with a mode of social security (profit or being entitled) Exclusion Criteria: An allergy or hypersensitivity to monoclonal antibodies or either of the study drugs (rituximab, abatacept or tocilizumab) or to their excipients A previous treatment with a combination of rituximab plus a cDMARD, with abatacept, or with tocilizumab A contraindication to a combination of rituximab plus a cDMARD, to abatacept, or to tocilizumab (including an ongoing infection; history of recent cancer <5 years before enrollment, except for cured non-melanoma skin cancer); pregnancy; and breastfeeding. Patients with severe vasculitis manifestations that requires plasma exchange therapy including severe renal failure with a creatinine level ≥350 µmol/L or severe alveolar haemorrhage Patients with vasculitis in remission Patients with symptoms attributable to chronic and non-active GPA Patients with severe cardiac failure defined as class IV in New York Heart Association Patients with acute infections or chronic active infections (including HIV, HBV or HCV) Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment Pregnant women and lactation. All women with childbearing potential are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception from the date of consent through the end of the study, and for women who are taking abatacept through 14 weeks after the last treatment administration, for women who are taking tocilizumab through 3 months after the last treatment administration, for women who are taking rituximab in combination with methotrexate through 6 months after the last treatment administration, for women who are taking rituximab in combination with mycofenolate mofetil or with azathioprine through 3 months after the last treatment administration Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol Patients included in other investigational therapeutic study within the previous 3 months Patients suspected not to be observant to the proposed treatments Laboratory parameter exclusions aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) > 5 times upper limit of normal Platelet count <100.000/mm3 White blood cell count <2000/mm3

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jonathan London, MD

Phone

+33 1 44 64 16 02

jlondon@hopital-dcss.org

First Name & Middle Initial & Last Name or Official Title & Degree

Audrey Beclin-Clabaux

Phone

+331 58 41 33 82

audrey.clabaux@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benjamin Terrier, MD, PhD

Organizational Affiliation

AP-HP - Service médecine interne

Official's Role

Study Director

Facility Information:

Facility Name

Hôpital de la Croix Saint Simon

City

Paris

ZIP/Postal Code

75020

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jonathan London, MD

Phone

+ 33 1 44 64 16 02

jlondon@hopital-dcss.org

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27338776

Citation

Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalcindag N, Jayne DR, Mukhtyar C. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94. doi: 10.1136/annrheumdis-2016-209133. Epub 2016 Jun 23. Erratum In: Ann Rheum Dis. 2017 Aug;76(8):1480. Ann Rheum Dis. 2022 Jun;81(6):e109.

Results Reference

background

PubMed Identifier

20647199

Citation

Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.

Results Reference

background

PubMed Identifier

22021864

Citation

Holle JU, Dubrau C, Herlyn K, Heller M, Ambrosch P, Noelle B, Reinhold-Keller E, Gross WL. Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. Ann Rheum Dis. 2012 Mar;71(3):327-33. doi: 10.1136/ard.2011.153601. Epub 2011 Oct 21.

Results Reference

background

PubMed Identifier

17170053

Citation

Hellmich B, Flossmann O, Gross WL, Bacon P, Cohen-Tervaert JW, Guillevin L, Jayne D, Mahr A, Merkel PA, Raspe H, Scott DG, Witter J, Yazici H, Luqmani RA. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis. 2007 May;66(5):605-17. doi: 10.1136/ard.2006.062711. Epub 2006 Dec 14.

Results Reference

background

PubMed Identifier

28733791

Citation

Sakai R, Kondo T, Kurasawa T, Nishi E, Okuyama A, Chino K, Shibata A, Okada Y, Takei H, Nagasawa H, Amano K. Current clinical evidence of tocilizumab for the treatment of ANCA-associated vasculitis: a prospective case series for microscopic polyangiitis in a combination with corticosteroids and literature review. Clin Rheumatol. 2017 Oct;36(10):2383-2392. doi: 10.1007/s10067-017-3752-0. Epub 2017 Jul 21.

Results Reference

background

PubMed Identifier

25841802

Citation

Berti A, Cavalli G, Campochiaro C, Guglielmi B, Baldissera E, Cappio S, Sabbadini MG, Doglioni C, Dagna L. Interleukin-6 in ANCA-associated vasculitis: Rationale for successful treatment with tocilizumab. Semin Arthritis Rheum. 2015 Aug;45(1):48-54. doi: 10.1016/j.semarthrit.2015.02.002. Epub 2015 Feb 20.

Results Reference

background

PubMed Identifier

31320177

Citation

Berti A, Warner R, Johnson K, Cornec D, Schroeder DR, Kabat BF, Langford CA, Kallenberg CGM, Seo P, Spiera RF, St Clair EW, Fervenza FC, Stone JH, Monach PA, Specks U, Merkel PA; RAVE-ITN Research Group. The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis. J Autoimmun. 2019 Dec;105:102302. doi: 10.1016/j.jaut.2019.07.001. Epub 2019 Jul 15.

Results Reference

background

PubMed Identifier

24323392

Citation

Langford CA, Monach PA, Specks U, Seo P, Cuthbertson D, McAlear CA, Ytterberg SR, Hoffman GS, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener's). Ann Rheum Dis. 2014 Jul;73(7):1376-9. doi: 10.1136/annrheumdis-2013-204164. Epub 2013 Dec 9.

Results Reference

background

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Study of Salvage Therapy to Treat Patients With Granulomatosis With Polyangiitis

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