Study to Evaluate Safety and Effectiveness of Anifrolumab Compared with Placebo in Male and Female Participants 18 to 70 Years of Age suffering from Systemic Sclerosis
- Conditions
- Health Condition 1: M340- Progressive systemic sclerosis
- Registration Number
- CTRI/2024/01/061867
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Demographic Characteristics
1Participant must be 18 to 70 years of age inclusive, at the time of signing the ICF.
2 Body weight = 145.0 kg (= 319.7 lb).
Disease Characteristics
3Participants with a confirmed classification of SSc according to 2013 ACR/EULAR classification criteria.
4 Limited or diffuse cutaneous subsets, as classified by Leroy and Medsger (Leroy and Medsger 2001).
5SSc disease duration = 6 years from first non-Raynaud’s phenomenon manifestation.
66 Either HAQ-DI score = 0.25 points or PtGA score = 3 points at Screening.
7mRSS > 10 at Screening with at least one of the following:
a Disease duration < 18 months
b Diagnosis of lung involvement (ILD) by chest CT confirmed by central reading assessment (no minimum) either via historical CT or CT performed during Screening
8If disease duration = 18 months and no confirmed ILD, mRSS must be = 15 AND active disease at Screening with at least one of the following:
a CRP = 6 mg/L (0.6 mg/dL) that is unrelated to other conditions (e.g., infection) or ESR = 28mm/hr or platelet count = 330 ×109 /L (330000/µL)
b New skin involvement or skin progression by mRSS = 3 units compared with the most recent assessment performed within the previous 6 months of signing the ICF
c Presence of at least one tendon friction rub documented in medical records within the previous 3 months of Screening and at Screening
9Participants may use one of the following standard immunosuppressant therapies at a stable dose prior to randomization (dose should be expected to remain stable throughout the course of the study) a,b
a Hydroxychloroquine (= 400 mg/day), methotrexate (= 25 mg/week), azathioprine (= 200 mg/day) at a stable dose for = 3 months prior to randomization
b MMF (= 3 g/day) or MPA (= 2.16 g/day) administered for = 6 months and at a stable dose for = 3 months prior to randomization
c Oral glucocorticoids (= 10 mg/day of prednisone or equivalent) at a stable dose for = 2 weeks prior to randomization
d Tacrolimus (= 0.2 mg/kg/day) administered for = 3 months prior to randomization; where local practice guidelines mandate or in case of safety concerns, monitoring of serum tacrolimus concentration may be performed at the discretion of investigator, with an aim of keeping a stable tacrolimus concentration targeting 5-10 ng/mL
MMF or MPA, azathioprine, methotrexate, and tacrolimus may be used in combination with hydroxychloroquine and/or low-dose oral glucocorticoids (= 10 mg/day)
Combinations of MMF or MPA, azathioprine, methotrexate, or tacrolimus with each other or with other conventional immunosuppressants are not permitted
10Uninvolved or mildly thickened skin (i.e., mRSS score of < 1) at one of the following possible injection-site locations:
A Anterior thigh
B Upper arm
C Abdomen
Sex and Contraceptive/Barrier Requirements
11Contraceptive use by females or males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a Female participants:
b Negative serum ß-hCG test at Screening (females of childbearing potential only).
c Women of childbearing potential must have a negative urine pregnancy test at randomization (Day 1), prior to administration of study intervention.
d F
1.Significant pulmonary hypertension defined by:
a. Previous clinical or echocardiographic evidence of right sided HF
b. History of right heart catheterization showing a cardiac index = 2 L/min/m²
c. PAH requiring parenteral therapy with epoprostenol/treprostinil or combination of oral & inhaled therapy
d. Class III or higher PAH
2.Anticentromere antibody seropositivity
3.History of SSc renal crisis within 12 months prior to signing the ICF or eGFR < 45 mL/min.
4.Overlap syndromes, SLE with anti-dsDNA antibody seropositivity or ACPA positive rheumatoid arthritis, or SSc mimics
5.History of, or current, any other inflammatory diseases, e.g.IBD, skin disease, that could interfere with efficacy & safety assessments or require immunomodulatory therapy.
6.History of any non-SSc disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF.
7.Pulmonary disease with FVC = 50% of predicted; or DLCO Hb = 45% of predicted (historical DLCO from up to 3 months prior to signing the ICF may be used); or Airway obstruction (pre-bronchodilator FEV1/FVC < 0.7)
8.Severe pulmonary disease
9.CVD with significant arrhythmia, CHF (NYHA Class II-IV), unstable angina, uncontrolled HT, cor pulmonale, symptomatic pericardial effusion, or cardiac abnormality such as LVEF < 50% at Screening.
10.History of thrombotic event within 12 months prior to signing the ICF.
11.Chest CT scan at Screening which shows:
(a)Evidence of current active infection or previous TB; or
(b)Evidence of malignancy; or
(c)Clinically significant non-SSc-related abnormalities.
12.History or evidence of suicidal ideation (severity of 4 or 5) within the past 6 months; or any suicidal behavior within past 12 months or recurrent suicidal behavior in the lifetime of the participant by C-SSRS at Screening or at baseline.
13.Moderately severe concurrent nervous system, renal, endocrine, hepatic, or gastrointestinal disease not related to SSc.
14.Other disease or conditions that may interfere with testing procedures or trial participation or may put the participant at risk.
15.Major surgery within 8 weeks prior to signing ICF or elective major surgery planned during the study period.
16.Hematopoietic stem cell transplantation or solid organ/limb transplantation.
17.Blood transfusion within 4 weeks prior to signing the ICF.
18.History of recurrent infection requiring hospitalization and IV antibiotics.
19.Any live or attenuated vaccine within 8 weeks prior to signing the ICF.
20.Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV infection.
21.Active HBV or HCV infection for:
a.HBsAg; or
b.HBcAb and HBV DNA or
c.HCV RNA.
22.Any severe case of HZ infection at any time prior to Week 0 (Day 1)
23.Any active CMV or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF.
24.Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years prior to signing the ICF.
25.Any of the following:
a.Clinically significant chronic infection within 8 weeks prior to signing the ICF
b.Any infectio
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method