Anifrolumab Asian PhIII Efficacy Study for Systemic Lupus Erythematosus (SLE)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04931563
• Collaborator: (none)
• Enrollment: 328
• Locations: 66
• Arms: 2
• Anticipated Duration (Months): 33
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Active Systemic Lupus Erythematosus	Biological: Anifrolumab; Drug: placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 328 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: double blind
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 13, 2021
• Anticipated Primary Completion Date: Jun 13, 2024
• Anticipated Study Completion Date: Jun 13, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo Placebo will be administered via controlled IV infusion pump into a peripheral vein over a minimum of 30 minutes Q4W from Week 0 to Week 48. Each dose must be at least 14 days apart.	Drug: placebo; Intravenous infusion (IV)
Active Comparator: anifrolumab Anifrolumab will be administered via controlled IV infusion pump into a peripheral vein over a minimum of 30 minutes Q4W from Week 0 to Week 48. Each dose must be at least 14 days apart.	Biological: Anifrolumab; Intravenous infusion (IV)

Outcome Measures

Primary Outcome Measures

1. Difference in proportion of participants who are responders between anifrolumab and placebo [Week 52]

   Composite endpoint (BICLA),a composite binary endpoint defined by meeting all of the following criteria: Reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, where worsening is defined as ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K No worsening from baseline in participants' lupus disease activity, where worsening is defined as an increase of ≥0.30 points on a 3-point PGA visual analogue scale (VAS) No discontinuation of investigational product No use of restricted medications beyond the protocol allowed threshold a before assessment

Secondary Outcome Measures

1. The proportion of participants who achieve Systemic Lupus Erythematosus Responder Index of ≥4 (SRI(4)) response [Week 52]

   SRI(4) response defined by meeting all of the following criteria: Reduction from baseline of ≥ 4 points in the SLEDAI-2K; No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items compared to baseline; No worsening from baseline in the participants' lupus disease activity defined by an increase ≥0.30 points on a 3-point PGA VAS; No discontinuation of investigational product No use of restricted medications beyond the protocol allowed threshold a before assessment

2. 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 [Week 52]

   Maintained OCS reduction defined by meeting all of the following criteria: Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 No discontinuation of investigational product No use of restricted medications beyond the protocol allowed threshold a before assessment

3. The proportion of participants with a ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score at Week 12 in the sub-group of those with baseline CLASI activity score ≥10 [Week 12]

   50% reduction in CLASI activity score compared to baseline defined by meeting all of the following criteria: Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline No discontinuation of investigational product No use of restricted medications beyond the protocol allowed threshold a before assessment

4. Annualized flare rate [Week 52]

   Annualised flare rate with flare defined as either 1 or more new BILAG-2004 A or 2 or more new BILAG-2004 B items compared to the previous visit

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

5. oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks;

6. Immunosuppressant(s) with or without OCS: antimalarials, AZA, MMF, MTX, mizoribine permitted; stable for ≥ 8 weeks; maximum dose required;

7. Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.

8. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.

9. 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.

10. Chest imaging shows no clinically significant abnormalities (unless due to SLE).

11. No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.

12. All participants should use effective contraception methods as protocol requests.

13. 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. Women participants with abnormal pap smear results.

12. Prior receipt of anifrolumab ,or any commercially available biologic agent, or protein kinase inhibitor or any investigational product within 5 half-lives, including B cell-depleting therapy, belimumab, JAK or BTK inhibitor.

13. Known history of allergy to any component of the IP formulation or protein related products.

14. Receipt of any of the following:

15. Intramuscular or IV glucocorticosteroids within 6 weeks;

16. Any live or attenuated vaccine within 8 weeks;

17. Any restricted medication listed in protocol;

18. 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.

19. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Baoding		China	071000
2	Research Site	Baotou		China	014010
3	Research Site	Beijing		China	100034
4	Research Site	Beijing		China	100144
5	Research Site	Beijing		China	100730
6	Research Site	Beijing		China
7	Research Site	Changchun		China	130033
8	Research Site	Changchun		China
9	Research Site	Changsha		China	410008
10	Research Site	Changsha		China	430033
11	Research Site	Changzhi		China	46000
12	Research Site	Chongqing		China	400038
13	Research Site	Chuangchun		China	130012
14	Research Site	Guangzhou		China	510080
15	Research Site	Guangzhou		China	510260
16	Research Site	Guilin		China	541001
17	Research Site	Jieyang		China	522000
18	Research Site	Jinan		China	250012
19	Research Site	Jining		China	272011
20	Research Site	Kunming		China	650032
21	Research Site	Luoyang		China	471003
22	Research Site	Nan Chong		China	637000
23	Research Site	Nanchang		China	330006
24	Research Site	Nanjing		China	210008
25	Research Site	Shanghai		China	200025
26	Research Site	Shengyang		China	110004
27	Research Site	Shenyang		China	110001
28	Research Site	Shenzhen		China	518020
29	Research Site	Suzhou		China	215006
30	Research Site	Tianjin		China	300052
31	Research Site	Urumqi		China	831118
32	Research Site	Wuhan		China	430022
33	Research Site	Wuhan		China	430030
34	Research Site	Xi'an		China	710061
35	Research Site	Xiamen		China	361003
36	Research Site	Zhengzhou		China	450052
37	Research Site	Hong Kong		Hong Kong	00000
38	Research Site	Hong Kong		Hong Kong
39	Research Site	Shatin		Hong Kong	00000
40	Research Site	Gwangju		Korea, Republic of	501-757
41	Research Site	Jung-gu		Korea, Republic of	41944
42	Research Site	Seoul		Korea, Republic of	03080
43	Research Site	Seoul		Korea, Republic of	04763
44	Research Site	Seoul		Korea, Republic of	143-729
45	Research Site	Seoul		Korea, Republic of	6591
46	Research Site	Suwon-si		Korea, Republic of	16499
47	Research Site	Davao City		Philippines	PH-8000
48	Research Site	Davao		Philippines	8000
49	Research Site	Iloilo City		Philippines	5000
50	Research Site	Lipa City		Philippines	4217
51	Research Site	Manila		Philippines	1000
52	Research Site	Manila		Philippines	1000
53	Research Site	Quezon City		Philippines	1112
54	Research Site	Kaohsiung		Taiwan	81362
55	Research Site	Kaohsiung		Taiwan	833
56	Research Site	Taichung City		Taiwan	402
57	Research Site	Taichung		Taiwan	40447
58	Research Site	Taichung		Taiwan	40705
59	Research Site	Taipei City		Taiwan	114
60	Research Site	Taipei		Taiwan	100
61	Research Site	Taipei		Taiwan	112
62	Research Site	Tao-Yuan		Taiwan	333
63	Research Site	Bangkok		Thailand	10400
64	Research Site	Bangkok		Thailand	10700
65	Research Site	Hat Yai		Thailand	90110
66	Research Site	Muang		Thailand	50200

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04931563
• Other Study ID Numbers: D3468C00003
• First Posted: Jun 18, 2021
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic

Study Results

No Results Posted as of Aug 1, 2022