E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
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E.1.1.1 | Medical condition in easily understood language |
Lupus, an autoimmune disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the pharmacokinetics and pharmacodynamics of anifrolumab. |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the safety and tolerability anifrolumab
2. To characterize the immunogenicity of anifrolumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18 through 70 years
2. Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11 ACR classification criteria with at least one being:
-Positive antinuclear antibody (ANA) or
-Elevated anti-dsDNA antibodies or
-anti-Smith (anti-Sm) antibodies
3. Interferon high test result
4. CLASI activity score ≥ 10
5. 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 ICFand with stable dosefor 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
6. Must not have signs of active or latent TB.
7. Must not be pregnant or breastfeeding
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E.4 | Principal exclusion criteria |
1. Active severe or unstable neuropsychiatric SLE
2. Active severe SLE-driven renal disease
3. Any severe herpes infection at any time
4. HBV, HCV, or HIV infection.
5. Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection
6. Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing of the ICF
7. History of cancer, apart from:
- Squamous or basal cell carcinoma of the skin if successfully treated
- Cervical cancer in situ if successfully treated
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E.5 End points |
E.5.1 | Primary end point(s) |
• Anifrolumab concentration and PK parameters, e.g., maximum concentration (Cmax) after first IP dose and trough concentration (Ctrough) after subsequent dosing. Additional PK parameters may be determined where appropriate.
• 21-gene type I IFN signature score and neutralization ratio (relative to baseline)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Safety and tolerability variables including:
• Adverse events (AEs) and serious adverse events (SAEs)
• Adverse events of special interest (AESIs) including herpes zoster, influenza, opportunistic infections, tuberculosis (TB), malignancies, non-SLE related vasculitis, anaphylaxis, and major adverse cardiovascular events (MACE)
• Laboratory variables
• Physical examinations
• Vital signs
• ECG
Immunogenicity as assessed by measurement of anti-drug antibodies (ADA).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Sponsor will be unblinded after all patients complete week 12 visit. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Hungary |
Korea, Republic of |
Poland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |