| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active Systemic Lupus Erythematosus |
|
| E.1.1.1 | Medical condition in easily understood language |
| Active Systemic Lupus Erythematosus |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| 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 |
|
| 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 |
| To evaluate the efficacy of AMG 570 at week 24 as measured by the Systemic Lupus Erythematosus Responder Index (SRI-4) in subjects with SLE with inadequate response to SOC therapy |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of AMG 570 with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy (key secondary).
- To evaluate the effect of AMG 570 on the efficacy response after 52 weeks of treatment (key secondary).
- To evaluate the effect of AMG 570 on additional SLE efficacy endpoints.
- To describe the effect of treatment with AMG 570 using patient reported outcome.
- To characterize the safety of AMG 570.
- To characterize the pharmacokinetics (PK) of AMG 570. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
- Age ≥ 18 years to ≤ 75 years at visit 1.
- Fulfills classification criteria for SLE according to the SLICC criteria or by at least 4 of the 11 criteria of the 1997 modification of the ACR classification criteria for SLE, with at least 1 of the following being present at screening: Antinuclear antibody ≥ 1:80; or Elevated anti-dsDNA antibodies by the Farr assay.
- SLEDAI-2K score ≥ 6 points with "Clinical" SLEDAI-2K score ≥ 4 points. The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures. For a subject whose clinical SLEDAI-2K score requires any of the following components, the subject must meet the following additional criteria:
o Arthritis: If a subject qualifies for the study by scoring for arthritis on the SLEDAI-2K form, they must have ≥3 swollen and/or tender joints in the hands or wrists, and the distribution should not involve the ankles, elbows, shoulders, or hips.
o Alopecia: Subjects scoring for alopecia on the SLEDAI-2K should have patchy hair loss without scarring; subjects should neither have alopecia areata nor androgenic alopecia.
o Oral ulcers: Subjects scoring for oral ulcers on the SLEDAI-2K should have physician documented location and appearance.
o Rash: To contribute to the minimally required clinical SLEDAI-2K score, rash must have been present for a minimum of 1 week, must cover at least 5% of the body surface area if discoid and 10% of the body surface area if any other type of lupus rash. Rash must have physician documented location and appearance.
- Must be taking at least 1 but not more than 2 of the following SLE treatments: mycophenolate mofetil, azathioprine, methotrexate, hydroxychloroquine, chloroquine, dapsone, or quinacrine. Treatment should be taken for ≥12 weeks prior to screening and must be a stable dose for ≥ 8 weeks prior to screening. Patients cannot be taking two immunosuppresants (ie, mycophenolate mofetil, azathioprine, or methotrexate) simultaneously.
- For subjects taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable ≥ 4 weeks prior to screening. |
|
| E.4 | Principal exclusion criteria |
- History of lupus nephritis requiring induction therapy within 1 year or active lupus nephritis (defined as any of the following: clean catch, spot urine protein creatinine ratio > 3000 mg/g at screening or active urinary sediment attributable to SLE).
- History of CNS lupus within 1 year prior to screening or active CNS lupus including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.
- Currently present or within 1 year prior to screening a diagnosis of any inflammatory joint or skin disease other than SLE (confirmed accurate by the PI) which would interfere with SLE disease assessment based on investigator judgement.
- History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 6 months prior to screening.
- Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1.
- Known history of active tuberculosis.
- Positive test for tuberculosis during screening defined as either positive or indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative (PPD) (≥ 5 mm of induration at 48 to 72 hours after test is placed).
- Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B DNA polymerase chain reaction [PCR] test) or detectable hepatitis C virus RNA by PCR (screening is generally done by hepatitis C antibody [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is positive). A history of hepatitis B vaccination without history of hepatitis B is allowed.
- Known history of HIV or positive serology for HIV antibodies at screening.
- Presence of 1 or more significant concurrent medical conditions per investigator judgment, including but not limited to the following:
o poorly controlled diabetes or hypertension (ie, systolic blood pressure > 170 mmHg and/or diastolic blood pressure > 100 mmHg)
o symptomatic heart failure (New York Heart Association class III or IV)
o myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization
o severe chronic pulmonary disease (eg, requiring oxygen therapy)
o multiple sclerosis or any other demyelinating disease
o major chronic inflammatory disease or connective tissue disease other than SLE (eg, RA, mixed connective tissue disease [MCTD], antiphospholipid antibody syndrome)
- Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent ≤ 6 months prior to day 1 OR oral calcineurin inhibitors (eg, cyclosporine, tacrolimus, sirolimus, voclosporin) ≤ 4 weeks prior to day 1.
- Currently receiving or had treatment with a JAK inhibitor or oral, targeted investigational agent (eg, Bruton’s tyrosine kinase inhibitor) < 3 months or 5 half-lives (whichever is longer) prior to day 1.
- Prior treatment with an immune checkpoint inhibitor (eg, PD-1 inhibitor, PD-L1 inhibitor, CTLA-4 inhibitor).
- Current or previous treatment for SLE with a biologic agent as follows: rituximab < 6 months prior to day 1 and undetectable B cell count; belimumab or anifrolumab < 6 months prior to day 1; abatacept < 6 months prior to day 1; or any other biologics < 5 half-lives prior to day 1.
- Subjects who have received intra-articular or systemic corticosteroid injections within 6 weeks prior to day 1.
- Currently receiving treatment in another investigational device or drug study.
- Ending a treatment or another investigation device or drug study(ies) less than 5 have-lives from the last dose of the investigational drug or 42 calendar days (whichever is longer) at day 1.
- Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 16 weeks after the last dose of investigational product.
- Female subjects of childbearing potential or female partners of male subjects unwilling to use 1 highly effective method of contraception during treatment and for an additional 16 weeks after the last dose of investigational product.
- Female subjects of childbearing potential with a positive pregnancy test (assessed by a serum pregnancy test at screening and a urine pregnancy test at baseline).
- Subject has known sensitivity to any of the products to be administered during dosing.
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator’s knowledge. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| - SRI-4 response at week 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- SRI-4 at week 52 with reduction of OCS to ≤ 7.5 mg/day by week 44 and sustained through week 52 in subjects with a baseline OCS dose ≥ 10 mg/day (key secondary).
- SRI-4 response at week 52 (key secondary).
- Tender and swollen joint count ≥ 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with ≥ 6 tender and ≥ 6 swollen joints at baseline.
- Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) activity score ≥ 50% improvement from baseline at week 12, 24, 36, and 52 in subjects with a CLASI score ≥ 10 at baseline.
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score and change from baseline at week 12, 24, 36, 44, and 52.
- Medical Outcomes Short Form 36 version 2 Questionnaire (SF36v2) score and change from baseline at week 12, 24, 36, 44, and 52.
- Modified Lupus QoL score and change from baseline at week 12, 24, 36, 44, and 52.
- Patient Global Assessment (PtGA) score and change from baseline at week 12, 24, 36, 44, and 52.
- Adverse events, Serious adverse events and Significant changes in laboratory values and vital signs. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Weeks 52 and 44
- Week 52
- Weeks 12, 24, 36 and 52
- Weeks 12, 24, 36 and 52
- Weeks 12, 24, 36, 44 and 52
- Weeks 12, 24, 36, 44 and 52
- Weeks 12, 24, 36, 44 and 52
- Weeks 12, 24, 36, 44 and 52
- Duration of the study |
|
| 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 |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| 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 |
| Australia |
| Austria |
| Bulgaria |
| Canada |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Italy |
| Japan |
| Korea, Republic of |
| Mexico |
| Poland |
| Portugal |
| Russian Federation |
| Switzerland |
| United Kingdom |
| United States |
|
| 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
|
End of Study: LVLS
Primary Completion: The primary completion date is defined as the date when the last subject is assessed or receives an intervention for the final collection of data for the primary endpoint(s), for the purposes of conducting the primary analysis, whether the study concluded as planned in the protocol or was terminated early. |
|
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | 16 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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