Anifrolumab Early Access Program - AMANA

Exclusion Criteria

• 1. Discontinued anifrolumab or placebo, for any reason including an AE, before completing Year 3 of the treatment period for study 09 or study 1145.
• 2. Major medical event, such as cerebrovascular accident (CVA), myocardial infarction (MI), malignancy, opportunistic infection, suicide attempt, or that, in the opinion of the Treating Physician, would interfere with patient safety.
• 3. Any other condition that, in the opinion of the Treating Physician, would interfere with patient safety.
• 4. Active severe or unstable neuropsychiatric SLE where, in the opinion of the Treating Physician, protocol-specified standard therapy is insufficient and utilisation of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.
• 5. Active severe SLE-driven renal disease where, in the opinion of the Treating. Physician or delegate, protocol-specified standard therapy is insufficient and utilisation of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.
• 6. Is receiving any of the following medications:
• a. Azathioprine > 200 mg/day
• b. Mycophenolate mofetil > 2 g/day or mycophenolic acid > 1.44 g/day
• c. Oral, subcutaneous (SC), or intramuscular (IM) methotrexate > 25 mg/week
• d. Oral prednisone > 40 mg/day (or prednisone equivalent – see Appendix E1)
• e. Mizoribine > 150 mg/day
• f. Biologics eg, belimumab, rituximab
• 7. Received any of the following:
• a. Live or attenuated vaccine within 8 weeks before signing the ICF. Note: administration of inactivated vaccines is acceptable – the Sponsor recommends that Treating Physicians ensure all patients are up to date on required vaccinations, including influenza (inactivated/recombinant) before EAP entry.
• b. Restricted medications listed in Appendix D if the washout period is not met.
• 8. Received any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives (whichever is greater) before signing the ICF (see Appendix D).
• 9. Received any commercially available biologic agent within 5 half-lives before signing ICF (see Appendix D).
• 10. Received B-cell-depleting therapy (including, but not limited to: ocrelizumab, ofatumumab, atacicept, obinutuzumab, rituximab) within 26 weeks before signing the ICF; within 40 weeks for atacicept (see Appendix D) or if therapy was administered 26 weeks or more ago (40 weeks for atacicept), absolute B-cell count should not be less than the lower limit of normal (LLN) or baseline (whichever is lower) before receipt of B-cell-depleting therapy.
• 11. Positive hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• 12. Known history of allergy or reaction to any component of anifrolumab or history of anaphylaxis to any human gamma globulin therapy.
• 13. COVID-19: Any history of severe COVID-19 infection (e.g. requiring hospitalisation, intensive care unit (ICU) care or assisted ventilation) or any prior COVID-19 infection with unresolved sequelae. Any acute COVID-19 infection (laboratory confirmed or suspected based on clinical symptoms) within the last 3 months prior to screening.
• Population B:
• Inclusion criteria:
• 1. Patients who have:
• a. Completed study D3461C0009 safety follow-up period (Week 164), and more than 12 weeks since Week 164 (safety follow-up visit 2);
• OR
• b. Completed safety follow-up period in phase 2 study CD1145;
• OR
• c. Not previously taken part in any anifrolumab clinical study and have attempted the standard therapeutic options at the maximum tolerated dose (see inclusion criterion 2);
• AND
• i. Are not eligible for enrollment in an anifrolumab clinical study,
• AND
• ii. Have moderate to severe SLE (no lupus nephritis or severe CNS lupus)
• 2. Attempted standard therapies, such as an antimalarial, therapeutic doses of oral corticosteroids, minimum of 2 immunosuppressants and biologics (belimumab or rituximab, if available in their country) from the following therapeutic options at the maximum tolerated dose:
• a. Azathioprine ≤ 200 mg/day
• b. Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine)
• c. Mycophenolate mofetil ≤ 2 g/day or mycophenolic acid ≤ 1.44 g/day
• d. Oral, SC, or IM methotrexate ≤ 25 mg/week
• e. Mizoribine ≤ 150 mg/day (Japan only)
• f. Oral prednisone or equivalent (see Appendix E1) ≤ 40 mg/day
• g. Biologics (eg, belimumab, rituximab).
• 3. Provided written informed consent before any program-related procedures are performed.
• 4. Adequate peripheral venous access.
• 5. Females of childbearing potential must use two effective methods of avoiding pregnancy, only one of which is a barrier method, from screening until 12 weeks after final dose of anifrolumab, unless the patient is surgically sterile (eg, bilateral oophorectomy or complete hysterectomy), has a sterile male partner, is at least 1-year postmenopausal, or practises sustained abstinence consistent with the patient’s customary lifestyle. Postmenopausal is defined as at least 1 year since last menses and the patient has an elevated FSH level greater than the local laboratory value of postmenopausal at screening – as detailed in Section 5.4.3.
• 6. All males (sterilised or non-sterilised) who are sexually active must use a condom (with spermicide where commercially available) from Day 1 (first dose of anifrolumab) until at least 12 weeks after receiving the final dose of anifrolumab. It is strongly recommended that the female partner of a male patient also uses an effective method of contraception (see Section 5.4.3) (other than a barrier method) throughout this period. Male patients must not donate sperm while taking part in the EAP and for 12 weeks after their last dose of anifrolumab – see Section 5.4.3 for further details.
• 7. Females with an intact cervix must have a documented normal Pap smear without documented malignancy (eg, no signs of CIN grade III, CIS or AIS) within 2 years of entering this EAP and receiving anifrolumab. Any abnormal Pap smear result documented within 2 years before receiving anifrolumb must be repeated to confirm patient eligibility.
• 8. COVID-19: Any negative PCR test result (central laboratory) at screening and no known or suspected COVID-19 exposure within 2 weeks prior to screening. If there is a known or suspected exposure, a patient must be negative upon retest obtained after 2 weeks and must remain asymptomatic for inclusion in the program. Note: Patients positive at screening may be re-screened after 3 months provided there has been no development of severe COVID-19 disease or sequalae.
• Exclusion criteria:
• 1. Discontinued anifrolumab or placebo before completing Year 3 of the treatment period for study D3461C0009 or study CD1145.
• 2. Major medical event, such as CVA, MI, malignancy, opportunistic infection, suicide attempt, or that, in the opinion of the Treating Physician, would interfere with patient safety.
• 3. Any condition that, in the opinion of the Treating Physician, would interfere with patient safety.
• 4. Active severe or unstable neuropsychiatric SLE where, in the opinion of the Treating Physician, protocol-specified standard therapy is insufficient and utilisation of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.
• 5. Active severe SLE-driven renal disease where, in the opinion of the Treating Physician or delegate, protocol-specified standard therapy is insufficient and utilisation of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.
• 6. Is receiving any of the following medications:
• a. Azathioprine > 200 mg/day
• b. Mycophenolate mofetil > 2 g/day or mycophenolic acid > 1.44 g/day
• c. Oral, SC, or IM methotrexate > 25 mg/week
• d. Oral prednisone > 40 mg/day (or prednisone equivalent – see Appendix E1)
• e. Mizoribine > 150 mg/day
• f. Biologics eg, belimumab, rituximab
• 7. Received any of the following:
• a. Live or attenuated vaccine within 8 weeks before signing the ICF. Note: administration of inactivated vaccines is acceptable – the Sponsor recommends that Treating Physicians ensure all patients are up to date on required vaccinations, including influenza (inactivated/recombinant) before EAP entry.
• b. Restricted medications listed in Appendix D if the washout period is not met.
• 8. Received any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives (whichever is greater) before signing the ICF (see Appendix D).
• 9. Received any commercially available biologic agent within 5 half-lives before signing ICF (see Appendix D).
• 10. Received B-cell-depleting therapy (including, but not limited to: ocrelizumab, ofatumumab, atacicept, obinutuzumab, rituximab) within 26 weeks before signing the ICF; within 40 weeks for atacicept (see Appendix D) or if therapy was administered 26 weeks or more ago (40 weeks for atacicept), absolute B-cell count should not be less than the LLN or baseline (whichever is lower) before receipt of B-cell-depleting therapy.
• 11. Positive hepatitis B, hepatitis C or HIV.
• 12. Known history of allergy or reaction to any component of anifrolumab or history of anaphylaxis to any human gamma globulin therapy.
• 13. COVID-19: Any history of severe COVID-19 infection (e.g. requiring hospitalisation, ICU care or assisted ventilation) or any prior COVID-19 infection with unresolved sequelae. Any acute COVID-19 infection (laboratory confirmed or suspected based on clinical symptoms) within the last 3 months prior to screening.