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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Proof of Concept (POC) Phase 2 Primary Objective:
To demonstrate a superior effect of BOS161721 at the chosen dose compared with placebo for response on the SRI-4. |
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E.2.2 | Secondary objectives of the trial |
POC Phase 2 Secondary Objectives:
To demonstrate a superior effect of BOS161721 at the chosen dose compared with placebo for response on clinical indicators of SLE activity, in adult patients with moderately to severely active SLE on limited background standard of care treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women, ages 18 to 70 years, inclusive 2. Patients must be mentally capable of giving consent and there must be evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study 3. Patients must have SLE as defined by meeting 4 of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE (with at least 1 clinical and 1 immunologic criterion OR Lupus nephritis as the sole clinical criterion in the presence of antinuclear antibodies [ANA] or anti- double-stranded deoxyribonucleic acid [dsDNA] antibodies), either sequentially or simultaneously 4. At screening, patients must have at least 1 of the following: a. Elevated ANA ≥ 1:80 via immunofluorescent assay at the central laboratory b. Positive anti-dsDNA or anti-Smith (Sm) above the normal level as determined by the central laboratory 5. At screening, the total SLEDAI-2K score must be ≥ 8, including points from at least 1 of the following clinical components: a. Arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, and vasculitis Note: Points from lupus headache and organic brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K scores at screening and Day 0. 6. A clinical SLEDAI-2K score of ≥ 6 at screening at Day 0. Clinical SLEDAI-2K score is defined as follows: a. Contains points from arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, or vasculitis b. Excludes parameters which require central laboratory results: hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia, and leukopenia Note: Points from lupus headache and organic brain syndrome will also be excluded from qualifying total and clinical SLEDAI-2K scores at screening and Day 0. 7. Patients must have at least 1 qualifying A or 2Bs from the following manifestations of SLE, as defined by the BILAG criteria as modified for use in this study, which must be confirmed by the central data reviewer: a. BILAG A or B score in the mucocutaneous body system. If a BILAG B score is due to BILAG number 6, mild skin eruption, the CLASI activity score including erythema and scale/hypertrophy must be ≥ 3 excluding points from mucosal ulcers and alopecia. b. BILAG A or B score in the musculoskeletal body system due to active polyarthritis as defined in the protocol Section 4.4 Note: Hips, shoulders, back, neck, and temporomandibular joints do not count towards the total number of joints with active synovitis. If only one “B” and no “A” score is present in the mucocutaneous body system or in the musculoskeletal body system due to arthritis, then at least 1 “B” must be present in at least 1 other body system for a total of 2 “B” BILAG body system scores. 8. Patients must be currently receiving at least 1 of the following: a. Administration for a minimum of 12 weeks, and a stable dose for at least 56 days (8 weeks prior to Day 0) of the following permitted steroid-sparing agents: i. Azathioprine (AZA), mycophenolate mofetil or mycophenolic acid, chloroquine, hydroxychloroquine, or methotrexate (MTX) b. If AZA, myocophenolate mofetil, mycophenolic acid, hydroxychloroquine, or MTX were discontinued prior to screening, the washout period must be ≥ 12 weeks. c. Corticosteroids (prednisone or prednisone-equivalent) at a stable dose of up to 30 mg/day for at least 6 weeks prior to Day 0 (see APPENDIX 3) i. For patients whose only SLE treatment is CSs, the stable CS dose must be ≥ 10 mg/day for at least 6 weeks prior to Day 0 and no more than 30 mg/day at the time of randomization. ii. Topical steroids may be used, but the dose must be stable for at least 6 weeks 9. Women of childbearing potential: a. Must have a negative serum pregnancy test at screening. Urine pregnancy test must be negative prior to first dose b. Must not be breastfeeding c. Must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of study drug BOS161721 plus 30 days (duration of ovulatory cycle) for a total of 36 weeks after treatment completion 10. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of BOS161721 plus 90 days (duration of sperm turnover) for a total of 44 weeks after treatment completion 11. Patients must demonstrate willingness and ability to comply with the scheduled study visits, treatment plans, laboratory tests, and other procedures |
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E.4 | Principal exclusion criteria |
1. Drug-induced SLE, rather than “idiopathic” SLE 2. Other systemic autoimmune disease a. RA-Lupus overlap and secondary Sjögren syndrome are allowed 3. Any major surgery within 6 weeks of study drug administration, (Day 0), or any elective surgery planned during the course of the study 4. Any history or risk for TB, specifically those with: a. Current clinical, radiographic, or laboratory evidence of active TB b. History of active TB c. Latent TB defined as positive QuantiFERON-TB Gold In-Tube (QFT-G) or other diagnostic test in the absence of clinical manifestations. Latent TB is not excluded if the patient has documented completion of adequate course of prophylactic treatment with regimen recommended by local health authority guideline, or the patient has started treatment with isoniazid, or other regimen recommended by local health authority guidelines for at least 1 month before Day 0 and continues to receive the prophylactic treatment during study until the treatment course is completed 5. Active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria, with the exception of mononeuritis multiplex and polyneuropathy, which are allowed 6. Severe proliferative lupus nephritis, which requires or may require induction treatment with cytotoxic agents or high dose CS 7. Concomitant illness that, in the opinion of the investigator,or the sponsor or their designee is likely to require additional systemic glucocorticosteroid therapy during the study, is exclusionary a. However, treatment for asthma with inhalational CS therapy is allowed 8. Use or planned use of concomitant medication outside of standard of baseline treatment for SLE from Day -1 or for any time during the study 9. Active and clinically significant infection within 60 days prior to first dose of study drug. Clinically significant is defined as requiring systemic parenteral antibiotics or hospitalization 10. A history of opportunistic infection, or a history of recurrent or severe disseminated herpes zoster or disseminated herpes simplex within the last 3 years 11. Chronic viral hepatitis including hepatitis B and hepatitis C unless patient received curative treatment for HCV and has a documented negative viral load, known human immunodeficiency virus, or acquired immunodeficiency syndrome (AIDS)-related illness 12. Cryptosporidium in the stool sample at screening 13. White blood cells (WBC) < 1,200/mm3 (1.2 × 109/L) at screening 14. Absolute neutrophil count (ANC) < 500/mm3 at screening 15. CD4+ count < 150/μL at screening 16. Platelets < 50,000/mm3 (50 × 109/L) or < 35,000/ mm3 (35 × 109/L) if related to SLE, at screening 17. Hemoglobin < 8 g/dL or < 7 g/dL at screening if related to SLE 18. Proteinuria > 3.0 g/day (3000 mg/day) at screening or equivalent level of proteinuria as assessed by protein/creatinine ratio (3 mg/mg or 339 mg/mmol) 19. Serum creatinine > 2.0 mg/dL at screening or creatinine clearance (CrCL) < 40 ml/minute based on Cockcroft-Gault calculation 20. Serum alanine aminotransferase and/or serum aspartate aminotransferase > 2 × the upper limit of normal at screening, unless explicitly related to lupus based on the investigator’s judgment 21. Creatinine kinase > 3.0 × ULN at screening unless related to lupus myositis 22. Total bilirubin > 1.5 × ULN at screening 23. Any other laboratory test results that, in the opinion of the Investigator or the sponsor or sponsor’s designee, might place a patient at unacceptable risk for participating in this study 24. History of allergic or anaphylactic reaction to any therapeutic or diagnostic mAb or molecules made of components of mAbs 25. History substance and/or alcohol abuse, or dependence within the past 1 year 26. History of cancer within the last 5 years 27. Any other severe acute or chronic medical or psychiatric condition that would make the patient inappropriate for entry into this study 28. Investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the investigator, or patients who are employees of the sponsor or directly involved in the conduct of the trial 29. Currently participating in, or who have participated in other interventional clinical study within 30 days or 5 half-lives of baseline, whichever is longer 30. Recent (within the past 12 months) or active suicidal ideation or behavior based on patient responding “yes” to question 3, 4, or 5 on the C-SSRS 31. Current or pending incarceration 32. Current or pending compulsory detainment for treatment of either a psychiatric or physical (eg, infectious disease) illness 33.Currently taking a total daily dose of > 30 mg morphine or morphine equivalent (see APPENDIX 7) 34.Body mass index (BMI) ≥ 40.0 |
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E.5 End points |
E.5.1 | Primary end point(s) |
POC Phase 2 Primary (Efficacy) Endpoints:
The proportion of patients with a SRI-4 response at Day 210. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints for evaluation of POC primary endpoints are listed in the endpoint description above. |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints • The proportion of patients with: - SRI-4 response at each visit - SRI-5 and SRI-6 response at each visit (Section 6.3.4.2) - a sustained reduction from baseline of oral corticosteroid (CS) (≤ 107.5 mg/day and ≤< Day 0 dose) between Day 120150 and Day 210 - new or recurrent BILAG A flares (≥ 1 qualifying BILAG A or > 1 1 qualifying BILAG B) flares relative to baseline through Day 210 - PGA worsening - a BICLA response - a CLASI response - medication failures • Results and changes from baseline in: - CLASI - Total number of swollen joints,and tender joints, and active joints (swelling and tenderness in the same joint) in the ACR-28 joint count - SLEDAI-2K - SLICC/ACR damage index • Time to medication failure • Group mean percent reduction in corticosteroid administration from baseline Day 0 dose through Day 210 in patients receiving ≥ 7.5 mg/day prednisone equivalent at Day 0 • Duration of longest SRI-4 response • Time to first SRI-4 response • Time to first BILAG A flare (≥ 1 new or recurrent BILAG A or > 1 new or recurrent BILAG B) flare comparedrelative to baseline through Day 210 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints for evaluation of POC secondary endpoints are listed in the endpoint description above. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Argentina |
Colombia |
Mexico |
Peru |
Philippines |
United States |
Poland |
Bulgaria |
Romania |
Georgia |
Hungary |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of trial will be when last patient completes the safety follow-up visit at Day 270. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |