An Efficacy and Safety Study of Intravenous Anifrolumab to Treat Systemic Lupus Erythematosus in Pediatric Participants (SLE)
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| ClinicalTrials.gov Identifier: NCT05835310 |
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Recruitment Status :
Recruiting
First Posted : April 28, 2023
Last Update Posted : April 29, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Systemic Lupus Erythematosus | Biological: Anifrolumab Drug: Placebo | Phase 3 |
This study aims to characterize the pharmacokinetics, pharmacodynamics, efficacy, and safety of Anifrolumab solution for infusion compared with placebo solution for infusion in pediatric participants with severe active systemic lupus erythematosus who are on background standard of care therapy.
The study duration for a participant will be approximately 120 weeks, which includes:
- Screening period of up to 30 days.
- Part A consists of a four-week, double-blind, placebo-controlled, randomised, pharmacokinetic period.
- Part B is a double-blind, placebo-controlled, randomised, safety/efficacy period lasting 48 weeks (for rollover participants from Part A) or 52 weeks (for de novo participants).
- Part C is a 52-week open-label extension period.
- Part D is a 12-week, safety follow-up period.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 100 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of IV Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Moderate to Severe Active Systemic Lupus Erythematosus (SLE) While on Background Standard of Care Therapy |
| Actual Study Start Date : | March 14, 2024 |
| Estimated Primary Completion Date : | July 25, 2029 |
| Estimated Study Completion Date : | January 15, 2030 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Anifrolumab
Randomized participants will receive a single dose of Anifrolumab via IV infusion every 4 weeks
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Biological: Anifrolumab
Participants will receive a single dose of Anifrolumab via IV infusion.
Other Name: (MEDI-546) |
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Placebo Comparator: Placebo
Randomized participants will receive matching placebo via IV infusion
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Drug: Placebo
Participants will receive matching placebo via IV infusion |
- Part A - Maximum observed serum (peak) drug concentration (Cmax) [ Time Frame: Up to Day 29 ]The PK will be characterised and the dose of Anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
- Part A - Area under the serum concentration curve (AUC) [ Time Frame: Up to Day 29 ]The PK will be characterised and the dose of Anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
- Part A - Minimum observed serum concentration (Cmin) [ Time Frame: Up to Day 29 ]Evaluation of Cmin following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.
- Part A - Maximum observed serum (peak) concentration at steady-state (Css, max) [ Time Frame: Up to Day 29 ]Evaluation of Css, max following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.
- Part A - Area under the serum concentration-time curve at steady-state (AUCss) [ Time Frame: Up to Day 29 ]Evaluation of AUCss following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.
- Part A - Average serum concentration at steady-state (Css, avg) [ Time Frame: Up to Day 29 ]Evaluation of Css, avg following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.
- Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no) [ Time Frame: At Week 52 ]
BICLA response is defined as:
- Reduction of all baseline British Isles Lupus Assessment Group BILAG-2004 A to B/C/D and B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG- 2004 B.
- No worsening from baseline in SLEDAI-2K, defined as an increase from baseline of > 0 points.
- No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a PGA 3-point visual analogue scale (VAS).
- Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no) [ Time Frame: At Week 52 ]
SRI-4 response is defined as:
- ≥ 4-point reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score.
- No new organ systems affected as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG-2004 B items compared to baseline.
- No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a PGA 3-point VAS.
- Part B - Time to first flare in pediatric participants with moderate to severe active SLE [ Time Frame: Through Week 52 ]Time to first flare, where flare is defined as either ≥ 1 new BILAG-2004 A, or ≥ 2 new BILAG-2004 B items compared with the previous visit.
- Part - B Change from baseline through Week 52 in Anifrolumab serum concentration [ Time Frame: Baseline, Week 52 ]The PK of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
- Part - B Change from baseline through Week 52 in antidrug antibody (ADA) [ Time Frame: Baseline, Week 52 ]The immunogenicity of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
- Part - B Change from baseline through Week 52 in anti-dsDNA antibodies [ Time Frame: Baseline, Week 52 ]The PD of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
- Part - B Change from baseline through Week 52 in complement components and CH50 [ Time Frame: Baseline, Week 52 ]The PD of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
- Number of participants who are Pediatric Rheumatology International Trials Organization/American College of Rheumatology (PRINTO/ACR) childhood-onset systemic lupus erythematosus (cSLE) responders (yes/no) [ Time Frame: At Week 52 ]
PRINTO/ACR cSLE responders are defined as participants with at least 50% improvement in 2 of 5 core set outcome measures and no more than one of the remaining worsening more than 30%, where the core set measures are:
- ParentGA 21-circle VAS
- PGA 3-point VAS
- SLEDAI-2K
- PedsQL Generic Core (Physical Functioning Domain)
- Proteinuria
- Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose [ Time Frame: Baseline, Week 52 ]The efficacy of Anifrolumab vs placebo on OCS background dose in pediatric participants with moderate to severe active SLE will be characterized.
- All parts - Number of participants reporting suicidal ideation and/or suicidal behavior as per Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: From Week 0 until the follow-up visit (12 weeks post-last dose) ]The safety and tolerability of Anifrolumab in pediatric participants with moderate to severe active SLE will be assessed.
- All parts - Number of participants with adverse events [ Time Frame: From Week 0 until the follow-up visit (12 weeks post-last dose) ]The safety and tolerability of Anifrolumab in pediatric participants with moderate to severe active SLE will be assessed.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 5 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Participant's parent/caregiver/legally authorized representative and participant (if required per local country regulation) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Informed assent is to be provided by the participant per local country regulation.
- Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria.
- Participant should meet all of following tuberculosis (TB) criteria:
A. No signs or symptoms of active TB B. No medical history or past physical examinations suggestive of active TB C. No recent contact with a person with active TB or if there has been such contact, referral to a TB specialist for evaluation and initiation of treatment for latent TB, if warranted, prior to the first administration of study intervention in accordance with local SoC D. No history of latent TB without documented completion of treatment prior to initial screening visit
- Female participants of childbearing potential must have a negative pregnancy test at Screening.
- Female participants of childbearing and non-childbearing potential and male participants must adhere to the contraception methods.
- At screening, negative SARS-CoV-2 RT-PCR or antigen test result and no known or suspected COVID-19 infection or exposure between screening and randomization visits.
Exclusion Criteria:
- Known diagnosis of a monogenic form of SLE.
- History of, or current diagnosis of, clinically significant non-SLE-related vasculitides.
- History or evidence of suicidal ideation.
- History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.
- Any positive result on Screening for human immunodeficiency virus.
- Active hepatitis B surface antigen OR hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) or any severe case of Herpes Zoster infection.
- Any clinical cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF.
- History of severe COVID-19 infection requiring hospitalization, intensive care unit care, or assisted ventilation or any prior COVID-19 infection with unresolved sequelae. Any mild/asymptomatic COVID-19 infection (laboratory confirmed or suspected based on clinical symptoms).
- Prior use of Anifrolumab.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05835310
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
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| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT05835310 |
| Other Study ID Numbers: |
D3461C00030 |
| First Posted: | April 28, 2023 Key Record Dates |
| Last Update Posted: | April 29, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. |
| Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Systemic Lupus Erythematosus SLE Monoclonal Antibody Anifrolumab |
Parallel-group treatment Pediatric participants Standard of care therapy Intravenous |
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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |