Clinical trial NCT04931563: Anifrolumab Asian PhIII Efficacy Study for Systemic Lupus Erythematosus (SLE)
Official title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Anifrolumab in Asian Participants With Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Active Systemic Lupus Erythematosus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-06-18
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in Asian participants with active systemic lupus erythematosus (SLE).

Detailed description: This is a Phase III, multicenter, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of an intravenous treatment regimen of 300 mg anifrolumab versus placebo in participants with moderate to severe, autoantibody positive SLE while receiving SOC treatment. The study will be performed in participants aged 18 to 70 years of age.

Participants with a confirmed diagnosis of moderate to severe active SLE and are currently receiving SOC comprising of oral corticosteroids (OCSs) and/or antimalarial, and/or immunosuppressants, either alone or any combination of them, for a required duration of treatment at a stable dose, as described in the inclusion criteria shall be included. Participants must have eligible scores for SLEDAI-2K, BILAG-2004, and PGA as confirmed by the DACRT.

Eligible participants will be randomised in a 1:1 ratio to receive either a fixed intravenous dose of 300 mg anifrolumab plus SOC or placebo plus SOC every 4 weeks (Q4W) for a total of 13 doses (Week 0 to Week 48), with the primary endpoint evaluated at the Week 52 visit.

Eligibility criteria: Key inclusion criteria:

1. Aged 18 to 70 years.
2. Body weight ≥ 40 kg.
3. Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks.
4. Must be receiving at least one of the following SOC regimens at screening:

   1. oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for \> 2 weeks;
   2. Immunosuppressant(s) with or without OCS and must be stable for ≥ 8 weeks;
   3. Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.
5. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.
6. SLEDAI-2K score ≥ 6 points at screening and "Clinical" SLEDAI-2K score ≥4 points at both screening and Day1(randomisation), and BILAG with at least 1 level A organ system or 2 level B organ system, and PGA score ≥ 1.0 at screening.
7. Chest imaging shows no clinically significant abnormalities (unless due to SLE).
8. No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.
9. All participants should use effective contraception methods as protocol requests.
10. Any negative SARS-CoV-2 RT-PCR test result at screening and no known or suspected COVID-19 infection or exposure within 2 weeks prior to screening and between screening and randomisation visits.

Key exclusion criteria:

1. History or current diagnose of clinically significant non-SLE related vasculitis, severe or unstable neuropsychiatric SLE, active severe SLE-driven renal disease, catastrophic anti-phospholipid syndrome, inflammatory joint or skin disease other than SLE, non-SLE disease that has required treatment of certain dosage of corticosteroid.
2. History or evidence of suicidal ideation or suicidal behavior.
3. History or current diagnose of MTCD or overlap syndrome, unless overlap with RA or MTCD which has developed into SLE.
4. History of recurrent infection requiring hospitalization and IV antibiotics, or opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization, or clinically significant chronic infection within 3 months, or recent infection still under treatment.
5. History of immunodeficient condition, HIV positive included.
6. Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable, or hepatitis C antibody positive.
7. History of severe case of herpes zoster.
8. Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeks before screening.
9. Acute COVID-19 infection or history of severe COVID-19.
10. History of cancer, apart from cured squamous or basal cell carcinoma and cervical cancer in situ.
11. Female participants with abnormal pap smear results.
12. Prior receipt of anifrolumab ,or any commercially available Janus kinase (JAK) inhibitor ≤ 12 weeks or Bruton's tyrosine kinase (BTK) inhibitor ≤ 24weeks prior to signing the ICF; any investigational medicinal product(small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater.
13. Known history of allergy to any component of the IP formulation or protein related products.
14. Receipt of any of the following:

    1. Intramuscular or IV glucocorticosteroids within 6 weeks;
    2. Any live or attenuated vaccine within 8 weeks;
    3. Any restricted medication listed in protocol;
    4. Blood transfusion within 4 weeks. 15 Regular use of \> 1 NSAID within 2 weeks or receipt of fluctuating doses of a NSAID within 2 weeks.

16. Certain laboratory test results requirements. 17. Concurrent enrolment in another clinical study. 18. History or current alcohol, drug or chemical abuse within 1 year. 19. Major surgery within 8 weeks or planned elective major surgery.

Primary outcomes:
measure: Difference in proportion of participants who are responders between anifrolumab and placebo
timeFrame: Week 52
Secondary outcomes:
measure: The proportion of participants who achieve SRI(4) response at week 52
timeFrame: Week 52
measure: The proportion of participants who achieve an oral corticosteroid (OCS) dose ≤7.5 mg/day at Week 40, which is maintained through Week 52 in the subgroup of those with baseline OCS ≥10 mg/day
timeFrame: Week 52
measure: Annualized flare rate
timeFrame: Week 52
Other outcomes:
Locations:
city: Baoding
country: China
facility: Research Site
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Binzhou
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chuangchun
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guilin
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hengyang
country: China
facility: Research Site
city: Jieyang
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jining
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Nan Chong
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanyang
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shengyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Xinxiang
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zaozhuang City
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Iloilo
country: Philippines
facility: Research Site
city: Lipa City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Tao-Yuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
Study officials:
References: