Systemic Lupus ErythematosusPhase 2NCT02962960
A Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab in Adult Type I Interferon Test High Systemic Lupus Erythematosus Subject With Active Skin Manifestations
A Phase 2 study testing Anifrolumab in people with Systemic Lupus Erythematosus, run by AstraZeneca at 14 sites in 4 countries.
Trial summary
This study will be conducted to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of anifrolumab given via the subcutaneous (SC) route of administration in adult Systemic Lupus Erythematosus (SLE) subjects with a type I Interferon (IFN) test high result and active skin manifestations while… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Anifrolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 14 sitesin 4 countries
- Study dates
- 14 Feb 2017to 17 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 through 70 years
- Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11 American College of Rheumatology (ACR) classification criteria with at least one being:
- Positive antinuclear antibody (ANA) or
- Elevated anti-dsDNA antibodies or
- anti-Smith (anti-Sm) antibodies
- Interferon high test result
Show all 12Show fewer
- Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10
- Currently receiving at least 1 of the following for treatment of SLE:
- Oral prednisone or equivalent of ≤40 mg/day for a minimum of 2 weeks prior to signing the Informed Consent Form (ICF) and with stable dose for at least 2 weeks prior to randomization
- Any of the following medications for at least 12 weeks prior to signing the ICF, and at a stable doses for at least 8 weeks prior to randomization: (i) Azathioprine ≤200 mg/day (ii) Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day
- Must not have signs of active or latent tuberculosis (TB).
- Must not be pregnant or breastfeeding.
Who cannot join
- Active severe or unstable neuropsychiatric SLE
- Active severe SLE-driven renal disease
- Any severe herpes infection at any time
- Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV infection.
- Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection
- Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing of the ICF
Show all 9Show fewer
- History of cancer, apart from:
- Squamous or basal cell carcinoma of the skin if successfully treated.
- Cervical cancer in situ if successfully treated
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
United States6 sites
Research Site
Charlotte, North Carolina, 28204
Research Site
Houston, Texas, 77034
Research Site
Memphis, Tennessee, 38119
Research Site
New York, New York, 10019
Research Site
Orlando, Florida, 32810
Research Site
Thousand Oaks, California, 91360
South Korea4 sites
Research Site
Anyang-si, 14068
Research Site
Busan, 49241
Research Site
Daegu, 41944
Research Site
Gwangju, 61469
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Characterizing the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab Following Subcutaneous Administration in Adult Systemic Lupus Erythematosus Subjects With Type I Interferon Test High Result and Active Skin Manifestations.
This study will be conducted to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of anifrolumab given via the subcutaneous (SC) route of administration in adult Systemic Lupus Erythematosus (SLE) subjects with a type I Interferon (IFN) test high result and active skin manifestations while receiving Standard of Care (SOC) treatment. In addition, the efficacy of anifrolumab on SLE skin manifestations will be characterized.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Anifrolumab, Placebo
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnifrolumabDrug
subcutaneous administration every 2 weeks from week 0 to week 50
PlaceboDrug
subcutaneous administration every two weeks from week 0 to week 50
| Study group | Role | What they receive |
|---|---|---|
| Anifrolumab - Lower dose | Experimental | 1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50 Receives: Drug: Anifrolumab |
| Placebo matching for lower dose of Anifrolumab | Placebo comparator | 1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50 Receives: Drug: Placebo |
| Anifrolumab - Higher dose | Experimental | 2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50 Receives: Drug: Anifrolumab |
| Placebo matching for higher dose of Anifrolumab | Placebo comparator | 2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Concentration of Anifrolumab in Serum After First Dose
Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.
Measured: Week 0
Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab
Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).
Measured: Week 12
21-gene Type 1 IFN Signature Score (Fold-change)
21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. Levels of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control.
Measured: Week 12
21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)
21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. For each individual participant and assessment, the level of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control, as the median of 100-(((baseline-Week 12)/baseline)*100) for the 21 genes. At a population level, the results are presented as mean the above.
Measured: Week 12
Secondary outcomes (15)
Number of Participants With Antidrug Antibody (ADA)
Post-baseline ADA incidence based on the number of participants with Antidrug antibody (ADA)
Measured: Baseline to Week 52
Number of Participants With Neutralizing Antibodies (nAb)
Incidence of detectable nAb in post-baseline ADA positive participants.
Measured: Baseline to Week 52
Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)
Number of participants with any AEs (Adverse events), any SAEs (serious adverse events), and any adverse events of special interest (AESI) are summarized. More details are reported in the Adverse Events section.
Measured: Baseline to Week 52
Change From Baseline for Vital Signs
Change from baseline for vital signs.
Measured: Baseline to Week 60
Change From Baseline for Physical Examination
Physical examination is reported as change from baseline in body weight.
Measured: Baseline to Week 60
Change From Baseline for 12-lead ECG
The 12-lead ECG measurements were assessed by the investigators, and reported as normal, abnormal (not clinically significant [NCS]), abnormal (clinically significant [CS]), or not done.
Measured: Baseline to Week 52
Value of Haemoglobin Blood Test to Detect Change From Baseline
Change from baseline in haemoglobin blood tests are reported.
Measured: Baseline to Week 60
Value of Haematology Blood Tests to Detect Change From Baseline
Change from baseline in haematology blood tests (leucocytes [particle concentration], platelets [particle concentration]) are reported.
Measured: Baseline to Week 60
Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline
Change from baseline in protein-creatinine ratio urinalysis tests are reported.
Measured: Baseline to Week 60
Value of Total Protein Urinalysis Test to Detect Change From Baseline
Change from baseline in total protein urinalysis tests are reported.
Measured: Baseline to Week 60
Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
Change from baseline in clinical chemistry blood tests (Alanine Aminotransferase, Aspartate Aminotransferase) are reported.
Measured: Baseline to Week 60
Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
Change from baseline in clinical creatinine chemistry blood tests (serum) are reported.
Measured: Baseline to Week 60
Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline
Change from baseline in the Erythrocyte Sedimentation Rate (ESR) inflammatory marker is reported.
Measured: Baseline to Week 60
Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline
Change from baseline in Anti-Double Stranded DNA IgG (anti-dsDNA) is reported.
Measured: Baseline to Week 60
Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.
Change from screening in Hepatitis B core antibody was monitored during the study for participants tested positive at screening.
Measured: Baseline to Week 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2016 (estimated)
- Study start14 Feb 2017
- Primary completion22 Jan 2018
- Study completion17 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02962960
- Sponsor's protocol ID
- D3461C00008
- Status last verified
- Dec 2022
- First submitted
- 23 Sep 2016
- Last updated
- 12 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bruce IN, Nami A, Schwetje E, Pierson ME, Rouse T, Chia YL, Kuruvilla D, Abreu G, Tummala R, Lindholm C. Pharmacokinetics, pharmacodynamics, and safety of subcutaneous anifrolumab in patients with systemic lupus erythematosus, active skin disease, and high type I interferon gene signature: a multicentre, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Rheumatol. 2021 Feb;3(2):e101-e110. doi: 10.1016/S2665-9913(20)30342-8. Epub 2020 Nov 20.
PubMed 38279367
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Characterizing the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab Following Subcutaneous Administration in Adult Systemic Lupus Erythematosus Subjects With Type I Interferon Test High Result and Active Skin Manifestations.
- ClinicalTrials.gov ID
- NCT02962960
- Acronym / sponsor ID
- D3461C00008
- Conditions
- Systemic Lupus Erythematosus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2017 (actual)
- Primary completion
- 22 Jan 2018 (actual)
- Study completion
- 17 Dec 2018 (actual)
- First posted
- 15 Nov 2016 (estimated)
- Results
- Posted 18 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be conducted to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of anifrolumab given via the subcutaneous (SC) route of administration in adult Systemic Lupus Erythematosus (SLE) subjects with a type I Interferon (IFN) test high result and active skin manifestations while receiving Standard of Care (SOC) treatment. In addition, the efficacy of anifrolumab on SLE skin manifestations will be characterized.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Anifrolumab - Lower dose | Experimental | Drug: Anifrolumab1ml, once every second week, one subcutaneous injection as added to stand of care, from week 0 to week 50 |
| Placebo matching for lower dose of Anifrolumab | Placebo comparator | Drug: Placebo1ml, once every second week, one subcutaneous injection added to stand of care, from week 0 to week 50 |
| Anifrolumab - Higher dose | Experimental | Drug: Anifrolumab2×1ml, once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50 |
| Placebo matching for higher dose of Anifrolumab | Placebo comparator | Drug: Placebo2×1ml , once every second week, two subcutaneous injections as added to stand of care, from week 0 to week 50 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age 18 through 70 years
- Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11 American College of Rheumatology (ACR) classification criteria with at least one being:
- Interferon high test result
- Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10
- Currently receiving at least 1 of the following for treatment of SLE:
Key exclusion criteria (9 listed)
- Active severe or unstable neuropsychiatric SLE
- Active severe SLE-driven renal disease
- Any severe herpes infection at any time
- Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV infection.
- Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anifrolumabsubcutaneous administration every 2 weeks from week 0 to week 50 | Drug | Anifrolumab - Higher dose, Anifrolumab - Lower dose |
| Placebosubcutaneous administration every two weeks from week 0 to week 50 | Drug | Placebo matching for higher dose of Anifrolumab, Placebo matching for lower dose of Anifrolumab |
Primary outcome
Maximum Concentration of Anifrolumab in Serum After First Dose
Time frame: Week 0
Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.
Steady-state Serum Trough (Predose) Concentration (Ctrough) of Anifrolumab
Time frame: Week 12
Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).
21-gene Type 1 IFN Signature Score (Fold-change)
Time frame: Week 12
21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. Levels of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control.
21-gene Type 1 IFN Neutralization Ratio (Percent Suppression of Fold Change)
Time frame: Week 12
21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. For each individual participant and assessment, the level of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control, as the median of 100-(((baseline-Week 12)/baseline)*100) for the 21 genes. At a population level, the results are presented as mean the above.
15 secondary outcomes
Number of Participants With Antidrug Antibody (ADA)
Time frame: Baseline to Week 52
Number of Participants With Neutralizing Antibodies (nAb)
Time frame: Baseline to Week 52
Number AEs (Adverse Events) and SAEs (Serious Adverse Events), Including Adverse Events of Special Interest (AESI)
Time frame: Baseline to Week 52
Change From Baseline for Vital Signs
Time frame: Baseline to Week 60
Change From Baseline for Physical Examination
Time frame: Baseline to Week 60
Change From Baseline for 12-lead ECG
Time frame: Baseline to Week 52
Value of Haemoglobin Blood Test to Detect Change From Baseline
Time frame: Baseline to Week 60
Value of Haematology Blood Tests to Detect Change From Baseline
Time frame: Baseline to Week 60
Value of Protein-creatinine Urinalysis Test to Detect Change From Baseline
Time frame: Baseline to Week 60
Value of Total Protein Urinalysis Test to Detect Change From Baseline
Time frame: Baseline to Week 60
Value of Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
Time frame: Baseline to Week 60
Value of Creatinine Clinical Chemistry Blood Tests to Detect Change From Baseline (Serum)
Time frame: Baseline to Week 60
Value of Inflammatory Marker Panel Blood Tests to Detect Change From Baseline
Time frame: Baseline to Week 60
Value of Autoantibody Blood Panel Blood Tests to Detect Change From Baseline
Time frame: Baseline to Week 60
Number of Participants With Positive Hepatitis B Core Antibody Post-baseline.
Time frame: Baseline to Week 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38279367Bruce IN, Nami A, Schwetje E, Pierson ME, Rouse T, Chia YL, Kuruvilla D, Abreu G, Tummala R, Lindholm C. Pharmacokinetics, pharmacodynamics, and safety of subcutaneous anifrolumab in patients with systemic lupus erythematosus, active skin disease, and high type I interferon gene signature: a multicentre, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Rheumatol. 2021 Feb;3(2):e101-e110. doi: 10.1016/S2665-9913(20)30342-8. Epub 2020 Nov 20.
- SAP redactedLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anifrolumab in people with Systemic Lupus Erythematosus, run by AstraZeneca at 14 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, South Korea, Hungary, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Concentration of Anifrolumab in Serum After First Dose (time frame: Week 0). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02962960, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2023.