Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus

Amgen

Status and phase: Terminated; Phase 2

Conditions: Active Systemic Lupus Erythematosus

Treatments: Drug: Placebo; Drug: Efavaleukin Alfa; Other: Standard of Care

Study type: Interventional

Funder types: Industry

Identifiers

NCT04680637

20200234

Details and patient eligibility

About

The primary objective is to evaluate the efficacy and safety of efavaleukin alfa in subjects with active systemic lupus erythematosus.

Enrollment: 168 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Participant is aged between 18 and 75.
• Fulfills classification criteria for systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE with antinuclear antibody ≥ 1:80 by immunofluorescence on Hep-2 cells being present at screening.
• Hybrid SLEDAI score ≥ 6 points with a "Clinical" hSLEDAI score ≥ 4 points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine or immunologic parameters.
• British-Isles Lupus Assessment Group (BILAG) index score (BILAG 2004) of ≥ 1 A item or ≥ 2 B items.
• Must be taking ≥ 1 of the following SLE treatments (or regional equivalent): hydroxychloroquine, chloroquine, quinacrine, mycophenolate mofetil, azathioprine, methotrexate, dapsone, or oral calcineurin inhibitors, or OCS. A participant may enter the study on OCS alone (prednisone ≥ 10 mg/day or equivalent) only if the participant has previously documented trial of anti-malarial or immunosuppressant treatment for SLE. Participants must be on a stable dose for ≥ 8 weeks prior to screening for all antimalarials and immunosuppressants, with the exception of OCS doses which must be stable for ≥ 2 weeks prior to screening.
• For participants taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit and for ≥ 2 weeks prior to screening visit.
• Stability of SLE treatments: OCS and other immunosuppressants/immunomodulator agents and doses must be stable since screening visit.
• Disease activity: active disease as indicated by clinical hSLEDAI score ≥ 4 must be observed (clinical hSLEDAI score is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results including urine and immunologic parameters).

Exclusion criteria

• Lupus nephritis if any of the following are present: urine protein creatinine ratio ≥ 2000 mg/g (or equivalent) at screening, OR requiring induction therapy currently or within 1 year prior to screening, OR histological evidence (if available) of diffuse proliferative glomerulonephritis within 12 weeks prior to screening.

• Active CNS lupus within 1 year prior to screening 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 chronic inflammatory disease other than SLE (eg, rheumatoid arthritis) which would interfere with SLE disease assessment.

• History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 4 months prior to screening.

• Active infection (including chronic or localized infections) for which anti-infectives are indicated currently or within 4 weeks prior to screening visit OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to screening visit.

• Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.

• Positive test for tuberculosis during creening defined as: either a 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 (HBsAg); or positive for hepatitis B core antibody (HBcAb). A history of hepatitis B vaccination without history of hepatitis B infection (ie, positive hepatitis B surface antibody (HBsAb), negative HBsAg and negative HBcAb) is allowed.

• Positive for hepatitis C antibody.

• Known history of HIV or positive HIV test at screening.

• Presence of 1 or more significant concurrent medical conditions, including but not limited to the following:

  • poorly controlled diabetes (hemoglobin A1C > 7) 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 screening
  • severe chronic pulmonary disease requiring oxygen therapy
  • multiple sclerosis or any other demyelinating disease

• Any history of malignancy with the following exceptions:

• resolved non-melanoma skin cancers > 5 years prior to screening

• resolved cervical carcinoma > 5 years prior to screening

• resolved breast ductal carcinoma in situ > 5 years of screening

• Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent within 6 months prior to screening or sirolimus within 4 weeks prior screening.

• Currently receiving or had treatment with a Janus kinase (JAK) inhibitor within 3 months or less than 5 drug half-lives (whichever is longer) prior to screening.

• Currently receiving or had treatment with an immune checkpoint inhibitor (eg, programmed death 1 [PD-1] inhibitor, programmed death ligand 1 [PD-L1] inhibitor, cytotoxic T-lymphocyte associated protein 4 [CTLA-4] inhibitor).

Note: Abatacept is not considered a CTLA-4 inhibitor and is referred to below.

• Currently receiving or had treatment within 12 months prior to screening with T-cell depleting agents (eg, antithymocyte globulin, Campath).
• Currently receiving of had treatment with an interleukin 2 (IL-2) based therapy (eg, Proleukin).
• Current or previous treatment with a biologic agent with immunosuppressive/immunomodulatory activity as follows: rituximab within 6 months prior to screening; abatacept and belimumab within the past 3 months prior to screening; other biologics within < 5 drug half lives prior to screening.
• Participants who have received intraarticular, intralesional, or intramuscular corticosteroids within 2 weeks prior to screening or intravenous corticosteroids within 6 weeks prior to screening.
• Participants who have received live vaccines within 5 weeks prior to screening, or plan to receive live vaccines during the treatment period and up to 6 weeks after the end of treatment period in the study.
• Currently receiving treatment in another investigational device or drug study.
• Ending a treatment with an investigational drug or investigational device less than 3 months or 5 half-lives from the last dose of the investigational drug (whichever is longer) at screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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168 participants in 4 patient groups, including a placebo group

Placebo + Standard of Care

Placebo Comparator group

Treatment:

Other: Standard of Care

Drug: Placebo

Efavaleukin Alfa Dose Level One + Standard of Care

Experimental group

Treatment:

Other: Standard of Care

Drug: Efavaleukin Alfa

Efavaleukin Alfa Dose Level Two + Standard of Care

Experimental group

Treatment:

Other: Standard of Care

Drug: Efavaleukin Alfa

Efavaleukin Alfa Dose Level Three + Standard of Care

Experimental group

Treatment:

Other: Standard of Care

Drug: Efavaleukin Alfa