Systemic SclerosisPhase 3DAISYNCT05925803
Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
A Phase 3 study testing Anifrolumab (blinded) and Anifrolumab (unblinded, open label) in people with Systemic Sclerosis and Scleroderma, run by AstraZeneca at 150 sites in 23 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic sclerosis. The target population for this study includes patients who meet the 2013 American College of Rheumatology/European League Against Rheumatism… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Sclerosis, Scleroderma
- What is being tested?
- Anifrolumab (blinded) and Anifrolumab (unblinded, open label)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 314 participants
- Where
- 150 sitesin 23 countries
- Study dates
- 8 Nov 2023to 5 Apr 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients from 18 to 70 years of age inclusive
- Systemic sclerosis according to 2013 ACR/EULAR classification criteria
- Limited or diffuse cutaneous subsets
- Systemic sclerosis disease duration within 6 years from first non-Raynaud's phenomenon manifestation at the time of signing the ICF
- Either HAQ-DI score ≥ 0.25 points or PtGA score ≥ 3 points
- mRSS > 10 with early disease or rapid progression as defined by the protocol
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- mRSS ≥ 15 with disease duration ≥ 18 months and active disease as defined by the protocol
- Stable background therapies can be used including hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, mycophenolate sodium, mycophenolic acid, oral glucocorticoids or tacrolimus
- Women of childbearing potential with a negative urine pregnancy test
- Uninvolved skin at injection sites
Who cannot join
- Anticentromere antibody seropositivity on central laboratory
- Severe cardiopulmonary disease as defined by the protocol
- History of systemic sclerosis renal crisis within past 12 months (estimated glomerular filtration rate(eGFR) < 45 mL/min/1.73m2)
- Overlap syndromes, systemic lupus erythematosus with anti-double-stranded deoxyribonucleic acid antibody seropositivity or anti-citrullinated protein antibodies-positive rheumatoid arthritis, or SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
- History of, or current, any other inflammatory diseases, eg, inflammatory bowel disease, skin disease, that, in the opinion of the investigator, could interfere with efficacy and safety assessments or require immunomodulatory therapy
- Evidence of moderately severe concurrent nervous system, renal, endocrine, hepatic (eg, underlying chronic liver disease [Child Pugh A, B, C hepatic impairment]), or gastrointestinal disease (eg, clinical signs of malabsorption or needing parenteral nutrition) not related to SSc, as determined by the investigator
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- Hematopoietic stem cell transplantation or solid organ/limb transplantation
- Any severe case of Herpes Zoster infection as defined by the protocol
- Known malignancy or a history of malignancy within 5 years, with exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
- Major surgery within 8 weeks prior to and/or during study enrollment
- Known active current or history of recurrent infections
- Any condition that, in the opinion of the investigator or AstraZeneca, would interfere with the efficacy or safety evaluation of the study intervention or put participant at safety risk
Trial locations and contacts
150 sites in 23 countries.
150 sites in 23 countries
United States26 sites
Research Site
Allen, Texas, 75013
Research Site
Ann Arbor, Michigan, 48109
Research Site
Aurora, Colorado, 80045
Research Site
Babylon, New York, 11702
Research Site
Baltimore, Maryland, 21224
Research Site
Boca Raton, Florida, 33486
Research Site
Chicago, Illinois, 60611
Research Site
Chula Vista, California, 91910
Research Site
Cincinnati, Ohio, 45219
Research Site
Fort Lauderdale, Florida, 33309
Research Site
Gainesville, Florida, 32603
Research Site
Houston, Texas, 77030
Research Site
Jacksonville, Florida, 32216
Research Site
Kansas City, Kansas, 66160
Research Site
Los Angeles, California, 90095
Research Site
Margate, Florida, 33063
Research Site
New Haven, Connecticut, 06519
Research Site
New Orleans, Louisiana, 70121
Research Site
New York, New York, 10032
Research Site
Orange, California, 92868
Research Site
Pittsburgh, Pennsylvania, 15213
Research Site
Rochester, Minnesota, 55905
Research Site
Scottsdale, Arizona, 85259
Research Site
South Miami, Florida, 33143
Research Site
Tamarac, Florida, 33321
Research Site
Washington D.C., District of Columbia, 20007
Japan14 sites
Research Site
Bunkyō City, 113-8603
Research Site
Fukuoka, 812-8582
Research Site
Iruma-Gun, 350-0495
Research Site
Kanazawa, 920-8641
Research Site
Maebashi, 371-8511
Research Site
Nagasaki, 852-8501
Research Site
Nagoya, 457-0866
Research Site
Sapporo, 060-8638
Research Site
Sendai, 980-8574
Research Site
Shinjuku-ku, 160-8582
Research Site
Suita-shi, 565-0871
Research Site
Takatsuki-shi, 569-8686
Research Site
Toyoake-shi, 470-1192
Research Site
Yokohama, 236-0004
India10 sites
Research Site
Ahmedabad, 380006
Research Site
Delhi, 110060
Research Site
Gurugram, 122001
Research Site
Hyderabad, 500082
Research Site
Kolkata, 700020
Research Site
Mumbai, 400053
Research Site
Mysuru, 570004
Research Site
New Delhi, 11029
Research Site
Pune, 411001
Research Site
Secunderabad, 500003
China9 sites
Research Site
Beijing, 100191
Research Site
Beijing, CN-100730
Research Site
Guangzhou, 510100
Research Site
Guangzhou, 510530
Research Site
Hangzhou, 310014
Research Site
Lanzhou, 730000
Research Site
Shanghai, 200032
Research Site
Shanghai, 201210
Research Site
Tianjin, 300050
Italy8 sites
Research Site
Ancona, 60126
Research Site
Brescia, 25123
Research Site
Cona, 44124
Research Site
Milan, 20122
Research Site
Padova, 35128
Research Site
Roma, 00128
Research Site
Roma, 00168
Research Site
Roma, 161
France7 sites
Research Site
Bordeaux, 33076
Research Site
Brest, 29609
Research Site
Paris, 75020
Research Site
Paris, 75679
Research Site
Rennes, 35033
Research Site
Strasbourg, 67098
Research Site
Toulouse, 31059
Spain7 sites
Research Site
A Coruña, 15006
Research Site
Barcelona, 08003
Research Site
Barcelona, 08041
Research Site
Madrid, 28041
Research Site
Málaga, 29009
Research Site
Valencia, 46017
Research Site
Valencia, 46026
Hungary6 sites
Research Site
Budapest, 1023
Research Site
Budapest, 1027
Research Site
Budapest, 1138
Research Site
Debrecen, 4032
Research Site
Pécs, 7632
Research Site
Szeged, 6725
Israel6 sites
Research Site
Afula, 18101
Research Site
Haifa, 31048
Research Site
Haifa, 31096
Research Site
Jerusalem, 00000
Research Site
Kfar Saba, 4428164
Research Site
Ramat Gan, 52621
Mexico6 sites
Research Site
Chihuahua City, 31000
Research Site
Guadalajara, 44158
Research Site
Guadalajara, 44650
Research Site
Mexico City, 06700
Research Site
San Luis Potosí City, 78213
Research Site
San Luis Potosí City, 78250
Poland6 sites
Research Site
Bydgoszcz, 85-168
Research Site
Krakow, 30-002
Research Site
Krakow, 30-105
Research Site
Lodz, 90-549
Research Site
Sosnowiec, 41-200
Research Site
Warsaw, 00-874
Turkey (Türkiye)6 sites
Research Site
Ankara, 06100
Research Site
Ankara, 06230
Research Site
Antalya, 07059
Research Site
Center, 23200
Research Site
Kazımkarabekir, 01230
Research Site
Kocaeli, 41380
Canada5 sites
Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Montreal, Quebec, H3T 1E2
Research Site
Montreal, Quebec, H4J 1C5
Research Site
Québec, Quebec, G1V 4K5
Research Site
Toronto, Ontario, M5T 3L9
Germany5 sites
Research Site
Freiburg im Breisgau, 79106
Research Site
Mainz, 55131
Research Site
Minden, 32429
Research Site
Münster, 48149
Research Site
Tübingen, 72076
South Korea5 sites
Research Site
Busan, 49241
Research Site
Seoul, 03080
Research Site
Seoul, 04401
Research Site
Seoul, 04763
Research Site
Seoul, 137-701
Vietnam5 sites
Research Site
Hà Nội, 100000
Research Site
Hanoi, 10000
Research Site
Ho Chi Minh City, 700000
Research Site
Ho Chi Minh City, 70000
Research Site
Hochiminh, 70000
Romania4 sites
Research Site
Bucharest, 011172
Research Site
Bucharest, 020475
Research Site
Cluj-Napoca, 400006
Research Site
Iași, 700661
United Kingdom4 sites
Research Site
Cannock, WS11 2XY
Research Site
Leeds, LS7 4SA
Research Site
London, NW3 2QG
Research Site
Sheffield, S10 2JF
Austria3 sites
Research Site
Graz, 8036
Research Site
Innsbruck, 6020
Research Site
Vienna, 1090
Malaysia3 sites
Research Site
Kuala Lumpur, 59100
Research Site
Kuching, 93586
Research Site
Seremban, 70300
South Africa2 sites
Research Site
Parktown, 2193
Research Site
Pretoria, 0083
About this study
Official title: A Multicenter, Randomized, Parallel-group, Double-blind,Two-arm Phase III Study to Evaluate the Safety and Efficacy of Anifrolumab Compared With Placebo in Male and Female Participants 18 to 70 Years of Age Inclusive With Systemic Sclerosis
The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic sclerosis. The target population for this study includes patients who meet the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification for systemic sclerosis, either limited or diffuse cutaneous subsets, with a disease duration of less than 6 years from first non-Raynaud's phenomenon symptom.
Read the detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, Phase III study to evaluate the efficacy and safety of anifrolumab in the treatment of adult participants with Systemic Sclerosis (SSc) who may be taking one or a combination of protocol-specified standard therapies. The use of one of the following standard immunosuppressant therapies is permitted at a stable dose, but not mandated: hydroxychloroquine, mycophenolate mofetil (MMF), mycophenolic acid or mycophenolate sodium (MPA/MPS), methotrexate, azathioprine, tacrolimus, and oral glucocorticoids. MMF or MPA/MPS, azathioprine, and methotrexate may be used in combination with hydroxychloroquine and/or low-dose oral glucocorticoids [≤ 10 mg/day].
Approximately 306 eligible participants will be randomized in a 1:1 ratio to receive either anifrolumab (or matching placebo) given subcutaneously once weekly for 52 weeks. The study will be stratified by the following factors:
- Interstitial lung disease (ILD) (yes, no) at Week 0 (Day1);
- MMF or MPA/MPS use (yes ,no) at Week 0 (Day 1); and
- Disease duration, defined as the time from the first non-Raynaud's symptom attributable to SSc (<18 months, ≥ 18 months) at Week 0 (Day 1)
Study treatment will be administered subcutaneously via an accessorized prefilled syringe by study staff or by the participant or carer, either in the clinic or at home, with most doses being administered at home. The study consists of 4 periods: a 6-week screening period, a 52-week, double-blind, placebo-controlled period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. There are a total of 16 study visits with most visits in the treatment period occurring every 8 to 12 weeks. The periods are described below:
- Screening Period: This may involve one or more visits to the study site.
- Double Blind Treatment Period: Treatment Period when participants will receive once weekly injections of anifrolumab or matching placebo. Participation will involve in-clinic study visits at Weeks 0 (Day 1), 1, 4, 8*, 16, 24, 36, 48 and 52. *The visit at Week 8 may be either by telephone or in person.
- Open Label Treatment Period: At Week 52, all participants will be given anifrolumab (subcutaneous) once weekly for 52 weeks (last dose at Week 103). Participation will involve in-clinic study visits at Weeks 52, 53*, 56, 64, 76. 88 and 104. *The visit at Week 53 may be either by telephone or in person.
- Safety Follow-up Period: All participants will return to the clinic for a 12-week post treatment visit. This will occur post Double Blind Treatment Period (Week 52 or Double Blind Period early discontinuation) or post Open Label Treatment Period (Week 104 or Open Label Period early discontinuation).
- Conditions
- Systemic Sclerosis, Scleroderma
- Being tested
- Anifrolumab (blinded), Placebo (blinded), Anifrolumab (unblinded, open label)
- Keywords
- Systemic Sclerosis (SSc), Scleroderma, Anifrolumab, Limited, Diffuse, Cutaneous, Interstitial lung disease (ILD), Autoimmune diseases, Immune system diseases, Immunosuppressants, Systemic Sclerosis interstitial lung disease (SSc- ILD)
- Medical subject headings
- Scleroderma, Systemic, Scleroderma, Diffuse, Lung Diseases, Interstitial, Autoimmune Diseases, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anifrolumab (blinded)Combination product
Also called Treatment arm (blinded)
Anifrolumab treatment delivered subcutaneously, once weekly for 52 weeks
Placebo (blinded)Drug
Also called Placebo arm (blinded)
matched placebo delivered subcutaneously, once weekly for 52 weeks
Anifrolumab (unblinded, open label)Combination product
Also called Treatment arm (not blinded)
At Week 52, all patients will receive Anifrolumab subcutaneously once weekly for 52 weeks
| Study group | Role | What they receive |
|---|---|---|
| Anifrolumab (subcutaneous weekly injection) | Experimental | Anifrolumab subcutaneous injection once weekly Receives: Combination Product: Anifrolumab (blinded); Combination Product: Anifrolumab (unblinded, open label) |
| matched placebo control (subcutaneous weekly injection) | Placebo comparator | matched placebo control subcutaneous injection once weekly Receives: Drug: Placebo (blinded) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants responding to treatment based on the Revised Composite Response Index in Systemic Sclerosis (CRISS-25)
Number of participants meeting all the criteria:
- Improvement in at least 2 components (≥5% increase for percent predicted Forced Vital Capacity (FVC) and/or≥25% decrease for Modified Rodnan Skin Score (mRSS), Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment (PtGA), Clinician Global Assessment (CGA)
- Worsening in no more than one component (≥5% decrease percent predicted FVC and/or≥25% increase for mRSS, HAQ-DI, PtGA, CGA)
- No significant SSc-related event as defined by:
New scleroderma renal crisis New decline in percent predicted FVC≥15% in established interstitial lung disease or new percent predicted FVC below 80% predicted New onset of left ventricular failure requiring treatment New onset of pulmonary arterial hypertension requiring treatment Gastrointestinal dysmotility requiring enteral or parenteral nutrition Digital ischemia with gangrene, amputation, or hospitalization requiring treatment
-Otherwise, a participant is a non-responder
Measured: at Week 52
Secondary outcomes (16)
Change from baseline in mRSS
Change from baseline in mRSS score. The mRSS scoring ranges from 0 (normal) to 51 (severe).
Measured: at Week 52
Number of patients with improvement in individual revised Composite Response Index in Systemic Sclerosis (CRISS-25)
Number of participants who have improvements in the following improvement components, evaluated separately:
- ≥ 5% increase in percent predicted Forced Vital Capacity (FVC)
- ≥ 25% decrease in mRSS
- ≥ 25% decrease in HAQ-DI
- ≥25% decrease in PtGA
- ≥25% decrease in CGA
Measured: at Week 52
Change from baseline in chest computed tomography imaging
Change from baseline in quantitative interstitial lung disease score
Measured: at Week 52
Change from baseline in Scleroderma Skin Patient Reported Outcome
Change from baseline in the Scleroderma Skin Patient Reported Outcome scores
Measured: at Week 52
Change from baseline in FVC
- Change from baseline in FVC (ml) in patients with interstitial lung disease
- Change from baseline in FVC (ml) in all patients
Measured: at Week 52
Change from baseline in percent predicted FVC
- Change from baseline in percent predicted FVC in patients with interstitial lung disease
- Change from baseline in percent predicted FVC in all patient
Measured: at Week 52
Anifrolumab pharmacokinetic parameters in serum
Anifrolumab serum concentrations will be summarised using descriptive statistics at each visit. Due to sparse pharmacokinetic sampling, the pharmacokinetic assessment will be primarily based on observed serum trough concentrations (Ctrough)
Measured: Weeks 4, 16, 24, 36, 52, 56, 76, and 104 to follow-up (max 116 weeks)
Anifrolumab pharmacodynamics via changes in type I IFN 21-gene signature generated from blood
Type I Interferon inducible gene signature will be assessed by a 21-gene assay in whole blood. The suppression of the type I IFN 21-gene signature will be showed as a percent of baseline through study completion, during both the double-blind treatment and open label periods.
Measured: Double-blind treatment period: pre-dose (Day 1) Weeks 4, 16, 24, 52; open-label period: weeks 56, 76 and 104
Prevalence of anti-drug antibodies to Anifrolumab
Anti-drug antibodies and titer determination in anti-drug antibody positive participants. The presence of neutralizing anti-drug antibodies will also be tested in all anti-drug positive samples.
Measured: Weeks 4, 16, 24, 36, 52, 56, 76, and 104 to follow-up (max 116 weeks)
Incidence of adverse events
Adverse events (non-serious, serious, and adverse event of special interest (AESI)) are assessed as variables of safety and tolerability of anifrolumab.
The AESIs are non-opportunistic serious infections, opportunistic infections, malignancy, herpes zoster, Tuberculosis (TB) (including latent TB), injection site reactions, and major adverse cardiac events.
Measured: From screening to follow-up (max 126 weeks)
Incidence of abnormal vital signs
Change from baseline of pulse rate, blood pressure, respiration rate, and body temperature will be assessed by visit and treatment group including participants with treatment-emergent changes.
Measured: From screening to follow-up (max 126 weeks)
Incidence of abnormal laboratory parameters
Changes from baseline in haematology, clinical chemistry and lipid variables will be assessed by visit and treatment including participants with treatment-emergent changes.
Measured: From screening to follow-up (max 126 weeks)
Incidence of abnormal ECG findings
Observed values of heart rate, QRS duration, PR interval, RR interval and QT interval will be summarised by visit and treatment group including participants with clinically significant abnormal results.
Measured: From screening to end of treatment visit (max 110 weeks)
Incidence of abnormal physical exam findings
Changes from baseline in weight (kilograms) will be assessed by visit and treatment and medically significant changes from the screening physical examination will be recorded as adverse events.
Measured: From screening to follow-up (max 126 weeks)
Number of subjects with suicidal ideation and behavior and suicide attempts via Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is used to assess suicidal ideation, behavior, and suicide on a graded scale from 1 to 5. 1 indicates as low suicidal and 5 as high suicidal behavior.
Measured: From screening to follow-up (max 126 weeks)
Total score of Personal Health Questionnaire Depression Scale-8 (PHQD-8)
PHQ-8 is an 8-item self-report scale, all items are rated on a score of 0-3, for a total range of 0-24. PHQD-8 assesses symptoms of depression over the previous 2 weeks. Higher scores indicate more depressive symptoms.
Measured: From screening to follow-up (max 126 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2023
- Study start8 Nov 2023
- Primary completion6 Jan 2027 (estimated)
- Study completion5 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- Model description
- Subjects will be randomized in a 1:1 ratio to either anifrolumab or matching placebo for 52 weeks (double blind treatment period). At Week 52, all patients will be treated with Anifrolumab for 52 weeks (open label treatment period).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 314 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05925803
- Sponsor's protocol ID
- D3460C00002
- Other IDs
- 2023-505976-31, 2023
- Acronym
- DAISY
- Status last verified
- Sep 2026
- First submitted
- 2 Jun 2023
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AstraZeneca disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AstraZeneca group of companies sponsored clinical trials are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Lescoat A, Lecureur V, Gudjonsson JE, Khanna D. Systemic sclerosis: pathogenic mechanisms and their implications for treatment. Semin Immunopathol. 2025 Nov 11;47(1):39. doi: 10.1007/s00281-025-01065-6.
PubMed 41217519
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Parallel-group, Double-blind,Two-arm Phase III Study to Evaluate the Safety and Efficacy of Anifrolumab Compared With Placebo in Male and Female Participants 18 to 70 Years of Age Inclusive With Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT05925803
- Acronym / sponsor ID
- DAISY / D3460C00002
- Conditions
- Systemic Sclerosis, Scleroderma
- Keywords
- Systemic Sclerosis (SSc), Scleroderma, Anifrolumab, Limited, Diffuse, Cutaneous, Interstitial lung disease (ILD), Autoimmune diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 314 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2023 (actual)
- Primary completion
- 6 Jan 2027 (estimated)
- Study completion
- 5 Apr 2028 (estimated)
- First posted
- 29 Jun 2023 (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.
The purpose of this study is to evaluate the efficacy and safety of treatment with subcutaneous anifrolumab versus placebo in adult participants with systemic sclerosis. The target population for this study includes patients who meet the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification for systemic sclerosis, either limited or diffuse cutaneous subsets, with a disease duration of less than 6 years from first non-Raynaud's phenomenon symptom.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, Phase III study to evaluate the efficacy and safety of anifrolumab in the treatment of adult participants with Systemic Sclerosis (SSc) who may be taking one or a combination of protocol-specified standard therapies. The use of one of the following standard immunosuppressant therapies is permitted at a stable dose, but not mandated: hydroxychloroquine, mycophenolate mofetil (MMF), mycophenolic acid or mycophenolate sodium (MPA/MPS), methotrexate, azathioprine, tacrolimus, and oral glucocorticoids. MMF or MPA/MPS, azathioprine, and methotrexate may be used in combination with hydroxychloroquine and/or low-dose oral glucocorticoids [≤ 10 mg/day].
Approximately 306 eligible participants will be randomized in a 1:1 ratio to receive either anifrolumab (or matching placebo) given subcutaneously once weekly for 52 weeks. The study will be stratified by the following factors:
- Interstitial lung disease (ILD) (yes, no) at Week 0 (Day1);
- MMF or MPA/MPS use (yes ,no) at Week 0 (Day 1); and
- Disease duration, defined as the time from the first non-Raynaud's symptom attributable to SSc (<18 months, ≥ 18 months) at Week 0 (Day 1)
Study treatment will be administered subcutaneously via an accessorized prefilled syringe by study staff or by the participant or carer, either in the clinic or at home, with most doses being administered at home. The study consists of 4 periods: a 6-week screening period, a 52-week, double-blind, placebo-controlled period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. There are a total of 16 study visits with most visits in the treatment period occurring every 8 to 12 weeks. The periods are described below:
- Screening Period: This may involve one or more visits to the study site.
- Double Blind Treatment Period: Treatment Period when participants will receive once weekly injections of anifrolumab or matching placebo. Participation will involve in-clinic study visits at Weeks 0 (Day 1), 1, 4, 8*, 16, 24, 36, 48 and 52. *The visit at Week 8 may be either by telephone or in person.
- Open Label Treatment Period: At Week 52, all participants will be given anifrolumab (subcutaneous) once weekly for 52 weeks (last dose at Week 103). Participation will involve in-clinic study visits at Weeks 52, 53*, 56, 64, 76. 88 and 104. *The visit at Week 53 may be either by telephone or in person.
- Safety Follow-up Period: All participants will return to the clinic for a 12-week post treatment visit. This will occur post Double Blind Treatment Period (Week 52 or Double Blind Period early discontinuation) or post Open Label Treatment Period (Week 104 or Open Label Period early discontinuation).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized in a 1:1 ratio to either anifrolumab or matching placebo for 52 weeks (double blind treatment period). At Week 52, all patients will be treated with Anifrolumab for 52 weeks (open label treatment period).
| Arm | Type | Receives |
|---|---|---|
| Anifrolumab (subcutaneous weekly injection) | Experimental | Combination Product: Anifrolumab (blinded), Combination Product: Anifrolumab (unblinded, open label)Anifrolumab subcutaneous injection once weekly |
| matched placebo control (subcutaneous weekly injection) | Placebo comparator | Drug: Placebo (blinded)matched placebo control subcutaneous injection once weekly |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult patients from 18 to 70 years of age inclusive
- Systemic sclerosis according to 2013 ACR/EULAR classification criteria
- Limited or diffuse cutaneous subsets
- Systemic sclerosis disease duration within 6 years from first non-Raynaud's phenomenon manifestation at the time of signing the ICF
- Either HAQ-DI score ≥ 0.25 points or PtGA score ≥ 3 points
Key exclusion criteria (12 listed)
- Anticentromere antibody seropositivity on central laboratory
- Severe cardiopulmonary disease as defined by the protocol
- History of systemic sclerosis renal crisis within past 12 months (estimated glomerular filtration rate(eGFR) < 45 mL/min/1.73m2)
- Overlap syndromes, systemic lupus erythematosus with anti-double-stranded deoxyribonucleic acid antibody seropositivity or anti-citrullinated protein antibodies-positive rheumatoid arthritis, or SSc mimics (eg, scleromyxedema, eosinophilic fasciitis)
- History of, or current, any other inflammatory diseases, eg, inflammatory bowel disease, skin disease, that, in the opinion of the investigator, could interfere with efficacy and safety assessments or require immunomodulatory therapy
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 |
|---|---|---|
| Anifrolumab (blinded)Also: Treatment arm (blinded)Anifrolumab treatment delivered subcutaneously, once weekly for 52 weeks | Combination product | Anifrolumab (subcutaneous weekly injection) |
| Placebo (blinded)Also: Placebo arm (blinded)matched placebo delivered subcutaneously, once weekly for 52 weeks | Drug | matched placebo control (subcutaneous weekly injection) |
| Anifrolumab (unblinded, open label)Also: Treatment arm (not blinded)At Week 52, all patients will receive Anifrolumab subcutaneously once weekly for 52 weeks | Combination product | Anifrolumab (subcutaneous weekly injection) |
Primary outcome
Number of participants responding to treatment based on the Revised Composite Response Index in Systemic Sclerosis (CRISS-25)
Time frame: at Week 52
Number of participants meeting all the criteria: * Improvement in at least 2 components (≥5% increase for percent predicted Forced Vital Capacity (FVC) and/or≥25% decrease for Modified Rodnan Skin Score (mRSS), Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment (PtGA), Clinician Global Assessment (CGA) * Worsening in no more than one component (≥5% decrease percent predicted FVC and/or≥25% increase for mRSS, HAQ-DI, PtGA, CGA) * No significant SSc-related event as defined by: New scleroderma renal crisis New decline in percent predicted FVC≥15% in established interstitial lung disease or new percent predicted FVC below 80% predicted New onset of left ventricular failure requiring treatment New onset of pulmonary arterial hypertension requiring treatment Gastrointestinal dysmotility requiring enteral or parenteral nutrition Digital ischemia with gangrene, amputation, or hospitalization requiring treatment -Otherwise, a participant is a non-responder
16 secondary outcomes
Change from baseline in mRSS
Time frame: at Week 52
Number of patients with improvement in individual revised Composite Response Index in Systemic Sclerosis (CRISS-25)
Time frame: at Week 52
Change from baseline in chest computed tomography imaging
Time frame: at Week 52
Change from baseline in Scleroderma Skin Patient Reported Outcome
Time frame: at Week 52
Change from baseline in FVC
Time frame: at Week 52
Change from baseline in percent predicted FVC
Time frame: at Week 52
Anifrolumab pharmacokinetic parameters in serum
Time frame: Weeks 4, 16, 24, 36, 52, 56, 76, and 104 to follow-up (max 116 weeks)
Anifrolumab pharmacodynamics via changes in type I IFN 21-gene signature generated from blood
Time frame: Double-blind treatment period: pre-dose (Day 1) Weeks 4, 16, 24, 52; open-label period: weeks 56, 76 and 104
Prevalence of anti-drug antibodies to Anifrolumab
Time frame: Weeks 4, 16, 24, 36, 52, 56, 76, and 104 to follow-up (max 116 weeks)
Incidence of adverse events
Time frame: From screening to follow-up (max 126 weeks)
Incidence of abnormal vital signs
Time frame: From screening to follow-up (max 126 weeks)
Incidence of abnormal laboratory parameters
Time frame: From screening to follow-up (max 126 weeks)
Incidence of abnormal ECG findings
Time frame: From screening to end of treatment visit (max 110 weeks)
Incidence of abnormal physical exam findings
Time frame: From screening to follow-up (max 126 weeks)
Number of subjects with suicidal ideation and behavior and suicide attempts via Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: From screening to follow-up (max 126 weeks)
Total score of Personal Health Questionnaire Depression Scale-8 (PHQD-8)
Time frame: From screening to follow-up (max 126 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Derived from this study: PubMed 41217519Lescoat A, Lecureur V, Gudjonsson JE, Khanna D. Systemic sclerosis: pathogenic mechanisms and their implications for treatment. Semin Immunopathol. 2025 Nov 11;47(1):39. doi: 10.1007/s00281-025-01065-6.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AstraZeneca disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AstraZeneca group of companies sponsored clinical trials are accepting requests for IPD, but this does not mean all requests will be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
150 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anifrolumab (blinded) and Anifrolumab (unblinded, open label) in people with Systemic Sclerosis and Scleroderma, run by AstraZeneca at 150 sites in 23 countries.
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 10 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 150 sites in United States, Japan, India, China, Italy and 18 more countries. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants responding to treatment based on the Revised Composite Response Index in Systemic Sclerosis (CRISS-25) (time frame: at Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05925803, which also lists 1 linked publication.
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 30 Sep 2026.