Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified March 2026 by AstraZeneca
Sponsor
AstraZeneca
Information Provided by (Responsible Party)
AstraZeneca
Clinicaltrials.gov Identifier
NCT05925803
Other Study ID Numbers:
D3460C00002
First Submitted
June 1, 2023
First Posted
June 28, 2023
Last Update Posted
April 19, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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).

Condition or DiseaseIntervention/Treatment
Systemic SclerosisScleroderma
Combination Product: Anifrolumab (blinded)Drug: Placebo (blinded)

Study Design

Study TypeInterventional
Actual Enrollment314 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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
Study Start DateNovember 7, 2023
Actual Primary Completion Date7mos 3w from now
Actual Study Completion Date1yr 10mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Anifrolumab (subcutaneous weekly injection)
Anifrolumab subcutaneous injection once weekly
Combination Product: Anifrolumab (blinded)
Anifrolumab treatment delivered subcutaneously, once weekly for 52 weeks
matched placebo control (subcutaneous weekly injection)
matched placebo control subcutaneous injection once weekly
Drug: Placebo (blinded)
matched placebo delivered subcutaneously, once weekly for 52 weeks

Outcome Measures

Primary Outcome Measures
  1. 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 (&ge;5% increase for percent predicted Forced Vital Capacity (FVC) and/or&ge;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 (&ge;5% decrease percent predicted FVC and/or&ge;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&ge;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
Secondary Outcome Measures
  1. Change from baseline in mRSS
    Change from baseline in mRSS score. The mRSS scoring ranges from 0 (normal) to 51 (severe).
  2. 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: * &ge; 5% increase in percent predicted Forced Vital Capacity (FVC) * &ge; 25% decrease in mRSS * &ge; 25% decrease in HAQ-DI * &ge;25% decrease in PtGA * &ge;25% decrease in CGA
  3. Change from baseline in chest computed tomography imaging
    Change from baseline in quantitative interstitial lung disease score
  4. Change from baseline in Scleroderma Skin Patient Reported Outcome
    Change from baseline in the Scleroderma Skin Patient Reported Outcome scores
  5. Change from baseline in FVC
    1. Change from baseline in FVC (ml) in patients with interstitial lung disease 2. Change from baseline in FVC (ml) in all patients
  6. Change from baseline in percent predicted FVC
    1. Change from baseline in percent predicted FVC in patients with interstitial lung disease 2. Change from baseline in percent predicted FVC in all patient
  7. 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)
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Adult patients from 18 to 70 years of age inclusive 2. Systemic sclerosis according to 2013 ACR/EULAR classification criteria 3. Limited or diffuse cutaneous subsets 4. Systemic sclerosis disease duration within 6 years from first non-Raynaud's phenomenon manifestation at the time of signing the ICF 5. Either HAQ-DI score ≥ 0.25 points or PtGA score ≥ 3 points 6. mRSS \> 10 with early disease or rapid progression as defined by the protocol 7. mRSS ≥ 15 with disease duration ≥ 18 months and active disease as defined by the protocol 8. Stable background therapies can be used including hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, mycophenolate sodium, mycophenolic acid, oral glucocorticoids or tacrolimus 9. Women of childbearing potential with a negative urine pregnancy test 10. Uninvolved skin at injection sites Key
Exclusion Criteria
1. Anticentromere antibody seropositivity on central laboratory 2. Severe cardiopulmonary disease as defined by the protocol 3. History of systemic sclerosis renal crisis within past 12 months (estimated glomerular filtration rate(eGFR) \< 45 mL/min/1.73m2) 4. 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) 5. 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 6. 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 7. Hematopoietic stem cell transplantation or solid organ/limb transplantation 8. Any severe case of Herpes Zoster infection as defined by the protocol 9. 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 10. Major surgery within 8 weeks prior to and/or during study enrollment 11. Known active current or history of recurrent infections 12. 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

Contacts and Locations

Sponsors and CollaboratorsAstraZeneca
Locations
Research Site | Scottsdale Arizona, United States, 85259Research Site | Chula Vista California, United States, 91910Research Site | Los Angeles California, United States, 90095Research Site | Orange California, United States, 92868Research Site | Aurora Colorado, United States, 80045Research Site | New Haven Connecticut, United States, 06519Research Site | Washington D.C. District of Columbia, United States, 20007Research Site | Boca Raton Florida, United States, 33486Research Site | Fort Lauderdale Florida, United States, 33309Research Site | Gainesville Florida, United States, 32603Research Site | Jacksonville Florida, United States, 32216Research Site | Margate Florida, United States, 33063Research Site | South Miami Florida, United States, 33143Research Site | Tamarac Florida, United States, 33321Research Site | Chicago Illinois, United States, 60611Research Site | Kansas City Kansas, United States, 66160Research Site | New Orleans Louisiana, United States, 70121Research Site | Baltimore Maryland, United States, 21224Research Site | Ann Arbor Michigan, United States, 48109Research Site | Rochester Minnesota, United States, 55905Research Site | Babylon New York, United States, 11702Research Site | New York New York, United States, 10032Research Site | Cincinnati Ohio, United States, 45219Research Site | Pittsburgh Pennsylvania, United States, 15213Research Site | Allen Texas, United States, 75013Research Site | Houston Texas, United States, 77030Research Site | Graz , Austria, 8036Research Site | Innsbruck , Austria, 6020Research Site | Vienna , Austria, 1090Research Site | Ghent , Belgium, B-9000Research Site | Leuven , Belgium, 3000Research Site | Calgary Alberta, Canada, T2N 4Z6Research Site | Toronto Ontario, Canada, M5T 3L9Research Site | Montreal Quebec, Canada, H3T 1E2Research Site | Montreal Quebec, Canada, H4J 1C5Research Site | Québec , Canada, G1V 3M7Research Site | Beijing , China, 100191Research Site | Beijing , China, CN-100730Research Site | Guangzhou , China, 510100Research Site | Guangzhou , China, 510530Research Site | Hangzhou , China, 310014Research Site | Lanzhou , China, 730000Research Site | Shanghai , China, 200032Research Site | Shanghai , China, 201210Research Site | Tianjin , China, 300050Research Site | Bordeaux , France, 33076Research Site | Brest , France, 29609Research Site | Paris , France, 75020Research Site | Paris , France, 75679Research Site | Rennes , France, 35033Research Site | Strasbourg , France, 67098Research Site | Toulouse , France, 31059Research Site | Freiburg im Breisgau , Germany, 79106Research Site | Mainz , Germany, 55131Research Site | Minden , Germany, 32429Research Site | Münster , Germany, 48149Research Site | Tübingen , Germany, 72076Research Site | Budapest , Hungary, 1023Research Site | Budapest , Hungary, 1027Research Site | Budapest , Hungary, 1138Research Site | Debrecen , Hungary, 4032Research Site | Pécs , Hungary, 7632Research Site | Szeged , Hungary, 6725Research Site | Ahmedabad , India, 380006Research Site | Delhi , India, 110060Research Site | Gurugram , India, 122001Research Site | Hyderabad , India, 500082Research Site | Kolkata , India, 700020Research Site | Mumbai , India, 400053Research Site | Mysuru , India, 570004Research Site | New Delhi , India, 11029Research Site | Pune , India, 411001Research Site | Secunderabad , India, 500003Research Site | Afula , Israel, 18101Research Site | Haifa , Israel, 31048Research Site | Haifa , Israel, 31096Research Site | Jerusalem , Israel, 00000Research Site | Kfar Saba , Israel, 4428164Research Site | Ramat Gan , Israel, 52621Research Site | Ancona , Italy, 60126Research Site | Brescia , Italy, 25123Research Site | Cona , Italy, 44124Research Site | Milan , Italy, 20122Research Site | Padova , Italy, 35128Research Site | Roma , Italy, 00128Research Site | Roma , Italy, 00168Research Site | Roma , Italy, 161Research Site | Bunkyō City , Japan, 113-8603Research Site | Fukuoka , Japan, 812-8582Research Site | Iruma-Gun , Japan, 350-0495Research Site | Kanazawa , Japan, 920-8641Research Site | Maebashi , Japan, 371-8511Research Site | Nagasaki , Japan, 852-8501Research Site | Nagoya , Japan, 457-0866Research Site | Sapporo , Japan, 060-8638Research Site | Sendai , Japan, 980-8574Research Site | Shinjuku-ku , Japan, 160-8582Research Site | Shinjuku-ku , Japan, 162-8666Research Site | Suita-shi , Japan, 565-0871Research Site | Takatsuki-shi , Japan, 569-8686Research Site | Toyoake-shi , Japan, 470-1192Research Site | Yokohama , Japan, 236-0004Research Site | Kuala Lumpur , Malaysia, 59100Research Site | Kuching , Malaysia, 93586Research Site | Seremban , Malaysia, 70300Research Site | Chihuahua City , Mexico, 31000Research Site | Guadalajara , Mexico, 44158Research Site | Guadalajara , Mexico, 44650Research Site | Mexico City , Mexico, 06700Research Site | San Luis Potosí City , Mexico, 78213Research Site | San Luis Potosí City , Mexico, 78250Research Site | Groningen , Netherlands, 9713 GZResearch Site | Bydgoszcz , Poland, 85-168Research Site | Krakow , Poland, 30-002Research Site | Krakow , Poland, 30-721Research Site | Lodz , Poland, 90-549Research Site | Sosnowiec , Poland, 41-200Research Site | Warsaw , Poland, 00-874Research Site | Bucharest , Romania, 011172Research Site | Bucharest , Romania, 020475Research Site | Cluj-Napoca , Romania, 400006Research Site | Iași , Romania, 700661Research Site | Parktown , South Africa, 2193Research Site | Pretoria , South Africa, Research Site | Busan , South Korea, 49241Research Site | Seoul , South Korea, 03080Research Site | Seoul , South Korea, 04401Research Site | Seoul , South Korea, 04763Research Site | Seoul , South Korea, 137-701Research Site | A Coruña , Spain, 15006Research Site | Barcelona , Spain, 08003Research Site | Barcelona , Spain, 08041Research Site | Madrid , Spain, 28041Research Site | Málaga , Spain, 29009Research Site | Valencia , Spain, 46017Research Site | Valencia , Spain, 46026Research Site | Ankara , Turkey (Türkiye), 06100Research Site | Ankara , Turkey (Türkiye), 06230Research Site | Antalya , Turkey (Türkiye), 07059Research Site | Center , Turkey (Türkiye), 23200Research Site | Kazımkarabekir , Turkey (Türkiye), 01230Research Site | Kocaeli , Turkey (Türkiye), 41380Research Site | Cannock , United Kingdom, WS11 2XYResearch Site | Leeds , United 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