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Safety and efficacy of obinutuzumab in patients with active diffuse systemic sclerosis: a randomized, double-blind, placebo-controlled trial

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The trial focuses on patients with newly diagnosed or active diffuse Systemic sclerosis, a rare disease that causes the skin and internal organs to become thick and stiff. The study drug is obinutuzumab, given by an IV infusion, and it is being compared with a matching placebo. The medication is intended to reduce the scarring (fibrosis) that affects the skin and the lungs.

The purpose of the study is to see whether the drug can lower skin and lung scarring as measured by a score called the CRISS after about one year. Participants receive the assigned treatment at the start and then have regular clinic visits for safety checks and to assess how the disease is changing.

Over the following 360 days, patients have periodic evaluations that include simple questionnaires about health and breathing, as well as routine blood tests and imaging to watch for side effects. The trial records any serious problems that occur and tracks overall survival during the study period.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomisation and assignment to treatment

    After you join the study, you will be randomly assigned to receive either gazyvaro (obinutuzumab) or a placebo (saline solution). the assignment is done by the study staff and you will not know which one you receive.

  2. Step 2

    Baseline assessments (day 0)

    On the first day of the trial you will undergo a series of examinations to record your current condition, including skin evaluation, lung function tests, and quality‑of‑life questionnaires.

    These baseline measurements are used to compare later results.

  3. Step 3

    First medication infusion

    You will receive a single intravenous infusion of 1000 mg obinutuzumab (the active ingredient of gazyvaro) or an equivalent volume of placebo (0.9 % saline).

    The infusion is given through a vein and takes several minutes under medical supervision.

  4. Step 4

    Follow‑up visit and assessment (day 90)

    Approximately three months after the first infusion you will return for a follow‑up visit.

    The same set of skin, lung, and questionnaire assessments performed at baseline will be repeated.

    Any side effects or adverse events that occurred since the last visit will be recorded.

  5. Step 5

    Second medication infusion (if scheduled) and day 180 assessment

    Around six months after randomisation you may receive another infusion of the same dose, depending on the study protocol.

    On day 180 you will again undergo skin and lung evaluations and complete quality‑of‑life questionnaires.

    The study team will evaluate improvement using the revised criss score.

  6. Step 6

    Third medication infusion (if scheduled) and day 270 assessment

    Approximately nine months after randomisation another infusion may be administered.

    On day 270 you will repeat the clinical assessments and questionnaires.

    Safety monitoring continues throughout this period.

  7. Step 7

    Final medication infusion (if scheduled) and day 360 assessment

    At one year (day 360) a final infusion may be given, followed by the last set of assessments.

    The primary outcome is measured by the percentage of patients who achieve at least a 20 % improvement in the revised criss score.

    Additional data on skin, lung, and quality of life will be collected, and all adverse events up to this point will be documented.

Who can join the trial?

10 criteria

  • Be at least 18 years old (an adult).
  • Have a diagnosis of systemic sclerosis (SSc) that meets the official 2013 criteria from the American College of Rheumatology and EULAR.
  • Have the diffuse form of SSc, meaning skin thickening is widespread, as defined by specific medical guidelines.
  • Have had SSc for less than 8 years since the first symptom that is not Raynaud’s phenomenon, or show active disease according to the EUSTAR disease‑activity score.
  • Have a modified Rodnan skin score (mRSS) between 10 and 35 units at screening – this test measures how thick the skin is on different body areas.
  • May be taking an anti‑fibrotic medication (a drug that helps reduce scarring in the lungs), such as nintedanib.
  • Women who could become pregnant must have a negative pregnancy test and use reliable birth control during the study and for 18 months after it ends.
  • Be able to read and sign a written consent form agreeing to take part in the study.
  • Be enrolled in a social security system (through employment or other entitlement).
  • If you are already using mycophenolate or methotrexate for SSc, the dose must have been stable (unchanged) for at least 2 months before randomisation.

Who cannot join the trial?

26 criteria

  • No recent B‑cell depleting or anti‑plasma cell therapy: You cannot have taken drugs that lower B‑cells (such as obinutuzumab, rituximab, ocrelizumab, ofatumumab, bortezomib) within the last 9 months. If you had such a drug 9‑12 months ago, a blood test for CD19+ B‑cells must show more than 25 cells per microliter.
  • No recent use of strong immune‑suppressing medicines: You must not have taken cyclophosphamide, tacrolimus, cyclosporine, or voclosporin in the two months before screening.
  • No recent other biologic medicines: Biologic drugs that are not B‑cell depleting (for example belimumab, ustekinumab, anifrolumab, secukinumab, atacicept) cannot be used within two months before screening.
  • No recent JAK, BTK, or TYK2 inhibitor drugs or experimental agents: Medications such as baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, fenebrutinib, or any other investigational drug must not have been taken in the two months before screening.
  • No live vaccines recently: You cannot have received a live vaccine (for example certain flu or yellow‑fever vaccines) within 28 days before screening.
  • No high risk of serious bleeding or recent need for plasma exchange, IV immune‑globulin, or blood transfusion: Any condition that could cause major bleeding or required these treatments in the four weeks before screening excludes you.
  • No active COVID‑19 infection and must be fully vaccinated: If you have a current SARS‑CoV‑2 infection or are not fully vaccinated according to your country’s recommendations, you cannot join.
  • No uncontrolled serious medical illness: Any significant disease that is not well‑controlled and could interfere with the study will exclude you.
  • No HIV infection: Participants who are known to have HIV, or whose HIV status is unknown and will be tested, are excluded.
  • No active infection (except nail‑bed fungus): Any ongoing infection that required a hospital stay in the past 8 weeks, IV antibiotics in the past 8 weeks, or oral antibiotics in the past 2 weeks will exclude you.
  • No history of serious recurrent or chronic infection: Past repeated or long‑lasting serious infections are not allowed.
  • No history of progressive multifocal leukoencephalopathy (PML): PML is a rare, serious brain infection caused by the JC virus.
  • No recent cancer: You cannot have had any solid tumor, blood cancer, or carcinoma in situ within the past 5 years, except for non‑melanoma skin cancers that have been completely removed.
  • No major surgery with hospital stay recently: Any major operation that required hospitalization within the four weeks before screening excludes you.
  • No current or recent alcohol or drug misuse: Use of alcohol or drugs in a harmful way now, or within the past 12 months, disqualifies you.
  • No severe allergy to study drugs: If you have had a serious allergic (anaphylactic) reaction to monoclonal antibodies or to any ingredient of the study infusion, you cannot participate.
  • Blood test limits: You are excluded if any of the following are found:
    • AST or ALT (liver enzymes) more than 2.5 times the normal upper limit.
    • Neutrophil count (a type of white blood cell) below 1.5 × 10³ per microliter.
    • Positive hepatitis B surface antigen (active hepatitis B infection).
    • Positive hepatitis C antibody with detectable hepatitis C virus (active hepatitis C infection).
    • Hemoglobin (oxygen‑carrying protein) below 7 g/dL.
    • Platelet count (cells that help blood clot) below 50,000 per microliter.
    • Pregnancy, breastfeeding, or no effective contraception: Women who are pregnant, nursing, or not using reliable birth control during the study cannot take part.
    • Protected or incarcerated adults: Individuals under legal guardianship or who are in prison are excluded.
    • No participation in another experimental drug study recently: You must not have been in another investigational therapeutic trial within the three months before screening.
    • No prior CAR‑T cell therapy: CAR‑T is a specialized cellular treatment used for certain cancers; having received it excludes you.
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Investigated drugs

Gazyvaro (obinutuzumab) is an intravenous medicine that contains a special type of protein called a monoclonal antibody. This antibody attaches to a target on certain immune cells, helping to calm an over‑active immune system. In people with systemic sclerosis, the drug is being tested to see if it can reduce the thickening and scarring (fibrosis) of the skin and lungs. Participants in the trial receive this treatment to find out whether it can improve these symptoms compared with not receiving the active drug.

What is already known about the treatment

Obinutuzumab - It is given by intravenous infusion as a sterile solution for infusion; it is an approved medicine for certain blood cancers and is now being studied in clinical trials for systemic sclerosis. The drug works by attaching to the CD20 protein on B‑cells, which triggers the immune system to destroy these cells and reduces abnormal immune activity. It belongs to the class of anti‑CD20 monoclonal antibodies and is considered an immunosuppressive therapy. The current trial aims to see if it can lower skin and lung scarring in patients with diffuse systemic sclerosis.

Investigated diseases

Diffuse systemic sclerosis - Diffuse systemic sclerosis is a chronic autoimmune condition that causes hardening and thickening of the skin over large areas of the body. The disease often begins with swelling of the fingers and hands and can spread to the arms, trunk, and legs. Over time, excess collagen builds up in the skin and internal organs, leading to reduced flexibility and function. The lungs, kidneys, heart, and gastrointestinal tract may become involved as fibrosis progresses. Symptoms may gradually worsen, affecting daily activities and quality of life.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2025-524003-68-00Protocol codeAPHP230826Estimated enrolment74 patientsSponsorAssistance Publique Hopitaux De Paris

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