Systemic Sclerosis in AdultsPhase 2OBINUSSNCT07842523
Obinutuzumab in Systemic Sclerosis
A Phase 2 study testing Obinutuzumab in people with Systemic Sclerosis in Adults, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of this study is to determine if obinutuzumab is effective in systemic sclerosis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis in Adults
- What is being tested?
- Obinutuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2026to Jun 2030
- Phase
- Phase 2
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
- Adult patient (>/= 18 years old),
- Patient with a diagnosis of SSc, as defined by the American College of Rheumatology / EULAR 2013 criteria,
- Patient with a diffuse SSc, as defined according to Leroy et al.
- Patient with a SSc disease duration of less than 8 years (defined as time from first non-Raynaud phenomenon manifestation) or with an active SSc disease, as defined by EUSTAR disease activity score,
- Patient with a modified Rodnan skin score (mRSS) > /= 10 and < /= 35 units at screening,
- Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception during the treatment period and up to 18 months after stopping it Women are considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient
Show all 11Show fewer
- Patient able to give written informed consent prior to participation in the study,
- Affiliation to a social security scheme (profit or being entitled).
- If patients receive mycophenolate or methotrexate for SSc, these need to be on stable dose as follows:
- Mycophenolate mofetil/sodium: stable dose for at least 2 months prior to randomisation Methotrexate: stable dose and route of administration for at least 2 months prior to randomisation
- Anti-fibrotic drugs such as nintedanib is permitted
Who cannot join
- Any B-cell depleting (e.g., anti-CD20, anti-CD19) or anti-plasma cell therapy such as, but not limited to, obinutuzumab, rituximab, ocrelizumab, ofatumumab, or bortezomib less than 9 months prior to screening or during screening. If anti-CD20 or anti-CD19 therapy has been received between 9 and 12 months prior to screening, the peripheral CD19+ B-cell count must be over 25 cells/μL
- Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
- Any biologic therapy (other than anti-CD20, anti-CD19, or anti-plasma cell) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening
- Inhibitors of Janus-associated kinase (JAK), Bruton's tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening
- Any live vaccine during the 28 days prior to screening or during screening
- High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions during the 28 days prior the screening
Show all 32Show fewer
- Active infection with SARS-CoV-2 or patients not fully vaccinated following national recommendations against SARS-CoV-2
- Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
- HIV infection: for participants with unknown HIV status, HIV testing will be performed locally at screening if required by local regulations.
- Active infection of any kind, excluding fungal infection of the nail beds. Any major episode of infection that also fulfills any of the following criteria:
- Requires hospitalization during the 8 weeks prior to screening or during screening
- Requires treatment with IV antibiotics (or anti-infectives) during the 8 weeks prior to screening or during screening
- Requires treatment with oral antibiotics (or anti-infectives) during the 2 weeks prior to screening or during screening
- Antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary.
- History of serious recurrent or chronic infection
- History of progressive multifocal leukoencephalopathy (PML)
- History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years (Participants with non-melanomatous carcinomas of the skin that have been treated or excised and have resolved are eligible).
- Major surgery requiring hospitalization during the 4 weeks prior to or during screening
- Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening
- Intolerance or contraindication to study therapies, including any of the following:
- History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
- Any of the following laboratory parameters:
- AST or ALT above 2.5 upper limit normal range
- Neutrophils <1.5x103/mL
- Positive hepatitis B surface antigen (HBsAg) Participants who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring until 12 months after the last dose of obinutuzumab or placebo.
- Positive hepatitis C serology Participants with positive hepatitis C antibody test result with no detectable hepatitis C virus (HCV) RNA for at least 6 months after completion of antiviral therapy are eligible but will require monthly HCV RNA monitoring until 12 months after the last dose of obinutuzumab or placebo.
- Hemoglobin below 7 g/dL
- Platelet count below 50,000/L
- Pregnant or breastfeeding woman, or woman who refuses to use an effective contraception during the study course;
- Protected adults (including individual under legal guardianship by court order or curatorship) or adults deprived of liberty;
- Patient participating in another investigational therapeutic study in the 3 months preceding inclusion;
- Patients treated with CAR-T cell immunotherapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Hôpital Cochin
Paris, Île-de-France Region, 75014
Benjamin CHAIGNE, MD, 01 58 41 41 17 ext. +33, benjamin.chaigne@aphp.fr
About this study
Official title: Safety and Efficacy of Obinutuzumab in Systemic Sclerosis: a Phase II, Randomized, Double-blinded Versus Placebo-controlled Trial"
The purpose of this study is to determine if obinutuzumab is effective in systemic sclerosis
Read the detailed description
Systemic sclerosis (SSc) is a rare systemic autoimmune connective tissue-disease characterized by fibrosis, inflammation, and vasculopathy. SSc is responsible for skin fibrosis that can either be limited or diffuse. The latter phenotype of the disease is commonly associated with visceral involvement and therefore similar to graft versus host disease (GvHD) reaction. It can be life threatening in case of pulmonary or cardiovascular involvement. Nonetheless SSc remains a severe disease responsible for important disability and a poor quality of life.
B cell depletion and anti CD20 antibody (rituximab) have proven safety and efficacy in treating diffuse SSc. Obinutuzumab is a new generation anti-CD20 antibody for which efficacy and safety should be evaluated in SSc.
The OBINUSS trial was thus designed to evaluate obinutuzumab safety and efficacy in SSc.
- Conditions
- Systemic Sclerosis in Adults
- Being tested
- Obinutuzumab, Placebo
- Keywords
- Systemic sclerosis, obinutuzumab
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObinutuzumabDrug
1000mg of i.v obinutuzumab at D1, D15 and D180
PlaceboDrug
1000mg of i.v placebo at D1, D15 and D180
| Study group | Role | What they receive |
|---|---|---|
| Obinutuzumab | Experimental | 1000mg of i.v obinutuzumab at D1, D15 and D180 Receives: Drug: Obinutuzumab |
| Placebo | Placebo comparator | 1000mg of i.v placebo at D1, D15 and D180 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the percentage of patients achieving a 20% CRISS improvement from baseline in at least 3 of the 5-core set second step leasures if the Revised CRISS at 360 days.
Measured: 360 days
Secondary outcomes (25)
Mortality up to 360 days
Measured: 360 days
Occurrence of Adverse Events up to 360 days
Measured: At 90, 180, 270 and 360 days
Occurrence of Severe Adverse Events up to 360 days
Measured: At 90, 180, 270 and 360 days
Occurrence of AE of specific interest previously mentioned
The number of adverse events, expressed according to the Common Terminology Criteria for Adverse Events (CTCAE): CTCAE toxicity grading system per patient-year at days 180 and 360 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hospitalization resulting either from the disease or from a complication due to the study treatment.
- Gammaglobulin and CD19 levels at 90, 180, 270 and 360 days
Measured: At 90, 180, 270 and 360 days
Proportion of patients who achieved CRISS20 of the revised CRISS
Measured: At days 180 and 270
Proportions of patients who achieved 30%, 40%, 50% ,60%, 70%, 80%, 90% and 100% improvement from baseline in at least 3 of the 5 core set measures of the revised CRISS
Measured: At days 180, 270 and 360
Change in the Combined Response Index in Diffuse Systemic Sclerosis (CRISS) score.These scales range from 0 (minimum) to 1(maximum) points. Higher score mean better outcome
Measured: At days 180, 270 and 360
Change in Physicians visual analogue scales over 18 months
These scales range from 0 (minimum) to ten (maximum) points and will be performed at day 0, at 6, 12, and 18 months. Higher score mean better outcome. Higher score mean worse outcome
Measured: At 18 months
Change in patients visual analogue scales over 18 month
These scales range from 0 (minimum) to ten (maximum) points and will be performed at day 0, at 6, 12, and 18 months. Higher score mean better outcome
Measured: At 18 months
Change in modified Rodnan skin score
Range from 0 (minimum) to 100% (maximum). Higher score mean better outcome
Measured: At 90, 180, 270 and 360 days
Proportion of patients with an improved modified Rodnan skin score.
Measured: At 90, 180, 270, 360 days
Absolute change from baseline in Forced Vital Capacity FVC
to look for a difference in Pulmonary function tests between patients treated with obinutuzumab and placebo, changes in forced vital capacity FVC and DLCO (% predicted and ml)
Measured: At days 180, 270, and days 360
Absolute change from baseline in DLCO
to look for a difference in Pulmonary function tests between patients treated with obinutuzumab and placebo, changes in forced vital capacity FVC and DLCO (% predicted and ml)
Measured: At day 180, 270 and day 360
Proportion of patients with an active disease according to the EUSTAR SSc activity score.
Measured: At 90, 180, 270 and 360 days.
Time to treatment failure.
Defined as the time to one of the following events (whichever occurs first) occurring over the 48 weeks: death, absolute decline in %-predicted FVC >/= 10 relative to baseline, >/= 25% increase in mRSS and an increase in mRSS of 5 points, initiation or dose change of MTX/MMF due to clinically significant deterioration.
Measured: Over the 48 weeks
Change in skin transcriptome.
According to Khanna et al. Arthritis Rheumatol. 2019 Dec 10;72(1):125-136
Measured: At 360 days
Analysis of the mouth opening trajectory
Measured: At days 0, 90, 180, 270 and 360
SF-36 scale
range from 0 (minimum) to 100 (maximum) points and will be performed at day 0, at 6, 12, and 18 months. Higher score mean better outcome
Measured: At day 0, 90, 180, 270 and day 360
EQ5D5L scale
comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a five-point scale, from 1 (no problems) to 5 (extreme problems), with higher scores reflecting worse health status. The overall EQ-5D-5L utility index is derived using the French country-specific value set, with higher utility scores reflecting better health status
Measured: At day 0, 90, 180, 270 and day 360
HAQ-DI scale
range from 0 (minimum) to 3 (maximum) points. Higher score mean worse outcome
Measured: At day 0, 90, 180, 270 and day 360.
SHAQ scale
range from 0 (minimum) to 3 (maximum) points. Higher score mean worse outcome
Measured: At day 0, 90, 180, 270 and day 360.
Saint Georges Respiratory Hospital Questionnaire (SGRH)
range from 0 (minimum) to one hundred (maximum) points. Higher score mean worse outcome
Measured: At day 0, 90, 180, 270 and day 360
King Brief's Interstitial Lung Disease questionnaire (KBILD)
range from 0 (minimum) to 100 (maximum) points. Higher score mean better outcome
Measured: At day 0, 90, 180, 270 and day 360
Scleroderma skin patients reported outcome (SSPRO)
range from 0 (minimum) to 108 (maximum) points. Higher score mean worse outcome
Measured: At day 0, 90, 180, 270 and day 360
PRO self-administered questionnaire (ScleroID)
range from 0 (minimum) to 10 (maximum) points. Higher score mean worse outcome
Measured: At day 0, 90, 180, 270 and day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2026
- Study startNov 2026 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Sclerosis in AdultsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Luc MOUTHON, MD / PhD, Study chair, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07842523
- Sponsor's protocol ID
- APHP230826
- Other IDs
- 2025-524003-68, 2025
- Acronym
- OBINUSS
- Status last verified
- Sep 2026
- First submitted
- 3 Aug 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No