Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04058028
Recruitment Status : Not yet recruiting
First Posted : August 15, 2019
Last Update Posted : September 12, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The purpose of this study is to determine if AMG 570 could be a useful therapeutic agent in the current treatment landscape where subjects with systemic lupus erythematosus (SLE) have ongoing disease activity despite treatment with standard of care therapies.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus (SLE) Drug: AMG 570 Drug: Placebo for AMG 570 Phase 2

Detailed Description:
This is a Bayesian adaptive phase 2, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Subjects will be enrolled and randomized to receive one of 3 doses of AMG 570 or placebo. The randomization starts as 1:1:1:1 and then could be adapted at IA based on the clinical efficacy (Response Adaptive Randomization [RAR]) for allocating more subjects to more efficacious doses and fewer subjects to less efficacious doses. Randomization will be stratified by geographic region (North America + Western Europe vs ROW) and screening SLEDAI-2K score (greater than or equal to 10 or less than 10).

Study duration for a single subject will be 52 weeks(treatment period) plus the screening period and safety follow-up period. Study treatment will be administered Q2W with the final dose at week 50. Subjects will complete a 16-week follow-up period after the final assessment visit. The follow-up period will consist of 4 visits.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Dose Ranging Study to Evaluate the Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE) With Inadequate Response to Standard of Care (SOC) Therapy
Estimated Study Start Date : October 8, 2019
Estimated Primary Completion Date : November 28, 2021
Estimated Study Completion Date : October 9, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arm Intervention/treatment
Experimental: AMG 570, Dose A
Investigational product solution in vial
Drug: AMG 570
AMG 570 will be presented in 5 mL glass vial

Experimental: AMG 570, Dose B
Investigational product solution in vial
Drug: AMG 570
AMG 570 will be presented in 5 mL glass vial

Experimental: AMG 570, Dose C
Investigational product solution in vial
Drug: AMG 570
AMG 570 will be presented in 5 mL glass vial

Placebo Comparator: Placebo for AMG 570
Placebo Investigational product solution in vial
Drug: Placebo for AMG 570
Placebo for AMG 570 will be presented in 5 mL glass vial




Primary Outcome Measures :
  1. Per cent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 24. [ Time Frame: Week 24 ]
    The SRI-4 is a composite endpoint that requires a greater than or equal to 4-point decrease in the SLE Disease Activity Index 2000 (SLEDAI-2K), an absence of worsening in the British Isles Lupus Assessment Group (BILAG) instrument, and an absence of worsening in the Physician's Global Assessment of Disease Activity.


Secondary Outcome Measures :
  1. Per cent of patients with an improvement in tender and swollen join count greater than or equal to 50% amongst those with greater than or equal to 6 tender and greater than or equal to 6 swollen joints at baseline [ Time Frame: Week 12, 24, 36, 52 ]
    A 28-joint count will be used to evaluate the effect of AMG 570 on additional SLE efficacy endpoints.

  2. Per cent of patients who achieve a greater than or equal to 50% improvement from baseline in the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) activity score amongst those with a CLASI score greater than or equal to 10 at baseline. [ Time Frame: Week 12, 24, 36, 52 ]
    To evaluate the effect of AMG 570 on additional SLE efficacy endpoints

  3. Subject incidence of Adverse Events [ Time Frame: 52 weeks ]
    To characterize the safety of AMG 570

  4. Subject incidence of Serious adverse events [ Time Frame: 52 weeks ]
    To characterize the safety of AMG 570

  5. Number of Subjects with significant changes in laboratory values [ Time Frame: 52 weeks ]
    To characterize the safety of AMG 570

  6. Number of Subjects with significant changes in vital signs [ Time Frame: 52 weeks ]
    To characterize the safety of AMG 570

  7. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
    To describe the effect of treatment with AMG 570 using patient reported outcomes

  8. Medical Outcomes Short Form 36 version 2 Questionnaire (SF36v2) score change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
    To describe the effect of treatment with AMG 570 using patient reported outcomes

  9. Modified Lupus QoL score and change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
    To describe the effect of treatment with AMG 570 using patient reported outcomes

  10. Patient Global Assessment (PtGA) score change from baseline [ Time Frame: week 12, 24, 36, 44 and 52 ]
    This is an 11-point NRS with 0 indicating lowest disease and 10 highest disease activity.

  11. Serum AMG 570 trough concentrations [ Time Frame: 52 Weeks ]
    To characterize the pharmacokinetics (PK) of AMG 570

  12. AMG 570 terminal elimination half-life, if possible [ Time Frame: 52 weeks ]
    To characterize the pharmacokinetics (PK) of AMG 570

  13. SRI-4 at week 52 with reduction of OCS to less than or equal to 7.5 mg/day by week 44 and sustained through week 52 [ Time Frame: week 52 ]
    To evaluate the efficacy of AMG 570 with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.

  14. Per cent of patients achieving Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at week 52 [ Time Frame: Week 52 ]
    The SRI-4 is a composite endpoint that requires a greater than or equal to 4-point decrease in the SLE Disease Activity Index 2000 (SLEDAI-2K), an absence of worsening in the British Isles Lupus Assessment Group (BILAG) instrument, and an absence of worsening in the Physician's Global Assessment of Disease Activity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

Inclusion Criteria Screening Visit 1:

  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
  • Age greater than or equal to 18 years to less than or equal 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 greater than or equal to 1:80; or
  • Elevated anti-dsDNA antibodies by the Farr assay. Note: Classification criteria and disease severity requirements to be reviewed by Central Review team at screening
  • SLEDAI-2K score greater than or equal to 6 points with "Clinical" SLEDAI-2K score greater than or equal to 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:
  • Arthritis: If a subject qualifies for the study by scoring for arthritis on the SLEDAI-2K form, they must have greater than or equal to 3 swollen and/or tender joints in the hands or wrists, and the distribution should not involve the ankles, elbows, shoulders, or hips.
  • 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.
  • Oral ulcers: Subjects scoring for oral ulcers on the SLEDAI-2K should have physician documented location and appearance.
  • 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.

Note: Subjects must meet requirements for clinical SLEDAI-2K at V1 and V2 visits.

• 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 greater than or equal to12 weeks prior to screening and must be a stable dose for greater than or equal to 8 weeks prior to screening. Patients cannot be taking two immunosuppresants (ie, mycophenolate mofetil, azathioprine, or methotrexate) simultaneously.

Note: Serum drug levels will be drawn at the initial screening visit. Each subject screened must have detectable levels of relevant immunomodulators/immunosuppressants (mycophenolate mofetil, azathioprine, methotrexate, hydroxychloroquine, chloroquine, or dapsone).

• For subjects taking OCS, dose must be less than or equal to 20 mg/day of prednisone or OCS equivalent, and the dose must be stable greater than or equal to 4 weeks prior to screening;

Inclusion Criteria Screening Visit 2:

Subjects will undergo a second screening visit a minimum of 21 calendar days and not more than 35 calendar days following screening visit 1. Subjects may proceed to screening visit 2 even if serological elements (eg, drug levels) from screening visit 1 are not yet available. Screening visit 2 will assess the following:

  • For SLE treatments including immunomodulators, immunosuppressives, and/or OCS, doses must be stable (relative to V1), and subjects must be compliant per patient history.
  • Disease activity must be stable as indicated by clinical SLEDAI-2K score greater than or equal to 4 (clinical SLEDAI-2K score is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures).

Key Exclusion Criteria:

Disease Related:

  • History of lupus nephritis requiring induction therapy within 1 year or active lupus nephritis.
  • History of CNS lupus within 1 year prior to screening or active CNS lupus.

Other Medical Conditions:

  • 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 greater than 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 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) (greater than or equal to 5 mm of induration at 48 to 72 hours after test is placed).
  • A positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative QuantiFERON ® -TB or T-Spot test and negative chest X-ray.
  • 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:
  • Poorly controlled diabetes or hypertension
  • Symptomatic heart failure (New York Heart Association class III or IV)
  • Myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization
  • Severe chronic pulmonary disease (eg, requiring oxygen therapy)
  • Multiple sclerosis or any other demyelinating disease
  • Major chronic inflammatory disease or connective tissue disease other than SLE (eg, RA, mixed connective tissue disease [MCTD], antiphospholipid antibody syndrome)
  • Any history of malignancy with the following exceptions:
  • Resolved non-melanoma skin cancers greater than 5 years prior to screening
  • Resolved cervical carcinoma greater than 5 years prior to screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04058028


Contacts
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen

Additional Information:
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04058028     History of Changes
Other Study ID Numbers: 20170588
First Posted: August 15, 2019    Key Record Dates
Last Update Posted: September 12, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: http://www.amgen.com/datasharing

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Standard of Care therapies
Oral Corticosteroids
Inmunosuppressants
Inmunodulators
Systemic Lupus Erythematosus
B cell Activating Factor (BAFF)
Inducible T cell costimulator ligand (ICOSL)
Additional relevant MeSH terms:
Layout table for MeSH terms
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases