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

JRCT ID: jRCT2041210076

Registered date:01/10/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Active Systemic Lupus Erythematosus
• Date of first enrollment: 06/05/2021
• Target sample size: 320
• Countries of recruitment: United States,Japan,Korea, Republic of,Japan,Poland,Japan,Turkey,Japan,Greece,,Japan,Spain,Japan,Austria,Japan,Bulgaria,Japan,Chile,Japan,Colombia,Japan,France,Japan,Hong Kong,Japan,Italy,Japan,Mexico,Japan,Russian Federation,Japan,Switzerland,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

Placebo Comparator: Placebo + Standard of Care
Interventions: Drug: Placebo
Other: Standard of Care
Experimental: Efavaleukin Alfa Dose Level One + Standard of Care
Interventions: Drug: Efavaleukin Alfa
Other: Standard of Care
Experimental: Efavaleukin Alfa Dose Level Two + Standard of Care
Interventions: Drug: Efavaleukin Alfa
Other: Standard of Care
Experimental: Efavaleukin Alfa Dose Level Three + Standard of Care
Interventions: Drug: Efavaleukin Alfa
Other: Standard of Care

Outcome(s)

Primary Outcome

1. Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 52 [ Time Frame: Week 52 ]
SRI-4 response is defined as a greater than or equal to 4-point decrease in the hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score and no new British Isles Lupus Assessment Group (BILAG) 2004 A domain score and no greater than 1 new BILAG 2004 B scores compared with baseline; and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) VAS (scale 0 to 3).

Secondary Outcome

1. Percent of Participants Achieving a British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 24 and Week 52 [ Time Frame: Week 24 and Week 52 ]
BICLA response is defined as at least 1 gradation of improvement in baseline British Isles Lupus Assessment Group (BILAG) domain scores in all body systems with moderate or severe disease activity at entry (eg, all A [severe disease] domain scores falling to B [moderate], C [mild], or D [no activity], and all B domain scores falling to C or D); no new BILAG 2004 A domain score and no greater than 1 new BILAG 2004 B domain scores compared with baseline; less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3); and no initiation of non-protocol treatment.
2. Percent of Participants Achieving a Lupus Low Disease Activity State (LLDAS) Response at Week 52 [ Time Frame: Week 52 ]
LLDAS response is defined as a hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score <= 4 with no activity in major organsystems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, and fever) and no haemolytic anaemia or gastrointestinal activity; no new findings of lupus disease activity compared with the previous assessment; <= 1-point in Physician Global Assessment (PGA) (scale 0 to 3) current prednisolone-equivalent dosage <= 7.5 mg/day; and standard maintenance dosages of immunosuppressive drugs and approved biologics.
3. Percent of Participants with a Reduction of Oral Corticosteroid (OCS) to Less Than or Equal to 7.5 mg/day by Week 44 and Sustained Through Week 52in Participants with a Baseline OCS Dose >= 10 mg/day [ Time Frame: Week 52 ]
To evaluate the efficacy of efavaleukin alfa with oral corticosteroid (OCS)-tapering in subjects with SLE with inadequate response to SOC therapy.
4. Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 [ Time Frame: Week 24 ]
SRI-4 response is defined as a greater than or equal to 4-point decrease in the hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score; no new British Isles Lupus Assessment Group (BILAG) 2004 A domain score and no greater than 1 new BILAG 2004 B scores compared with baseline; and a less than 0.3-point deterioration from baseline in Physician Global Assessment (PGA) (scale 0 to 3).
5. Percent of Participants Achieving a Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) Response at Week 24 and Week 52[ Time Frame: Week 24 and Week 52 ]
hSLEDAI response is defined as a greater than or equal to 4-point decrease in score.
6. Tender and Swollen Joint Count >= 50% Improvement from Baseline at Weeks 8, 12, 24, 36, and 52 in Participants with >= 6 Tender and Swollen Joints Involving the Hands and Wrists at Baseline [ Time Frame: Baseline, Week 8, 12, 24, 36, and 52 ]
A 28-joint count will be used to evaluate the effect of efavaleukin alfa on additional SLE efficacy endpoints. A total 28 joints will be scored for presence or absence of swelling. A separated score for joints in the hands and wrists will be calculated
7. Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score >= 50% Improvement from Baseline at Week 8, 12, 24, 36, and 52 in Participants with a CLASI Activity Score >= 8 at Baseline [ Time Frame: Baseline, Week 8, 12, 24, 36, and 52 ]
To evaluate the effect of efavaleukin alfa on additional SLE efficacy endpoints
8. Percent of Participants who Experience a Flare [ Time Frame: Week 52 ]
A flare is defined as a British Isles Lupus Assessment Group (BILAG) score designation of 'worse' or 'new'.
9. Change from Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS Fatigue SF 7A)Fatigue Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes
10. Change from Baseline in Medical Outcomes Short Form-36 Questionnaire Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes
11. Change from Baseline in Lupus Quality of Life (QoL) Questionnaire Score [ Time Frame: Baseline, Week 12, 24, 36, and 52 ]
To describe the effect of treatment with efavaleukin alfa using patient reported outcomes
12. Number of Participants who Experience a Treatment-Emergent Adverse Event (AE) and Serious Adverse Event (SAE) [ Time Frame: Up to Week 56 ]
To characterize the safety of efavaleukin alfa
13. Number of Participants who Experience a Clinically Significant Change in Laboratory Values and Vital Sign Measurements [ Time Frame: Up to Week56 ]
To characterize the safety of efavaleukin alfa
14. Trough Serum and Sparse Postdose Serum Concentration of efavaleukin alfa [ Time Frame: Up to Week 52 ]
To characterize the pharmacokinetics (PK) of efavaleukin alfa

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

1. Participant has provided informed consent prior to initiation of any study specific activities/procedures.
2. Participant is aged between 18 and 75.
3. 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.
4. 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.
5. British-Isles Lupus Assessment Group (BILAG) index score (BILAG 2004) of >= 1 A item or >= 2 B items.
6. 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 as table 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.
7. 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 week sprior to screening visit.
8. Stability of SLE treatments: OCS and other immunosuppressants/immunomodulator agents and doses must be stable since screening visit.
9. 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).

Exclude criteria

1. 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.
2. 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.
3. 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.
4. 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.
5. Active infection (including chronic or localized infections) for which anti-infectives are indicated currently 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.
6. Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.
7. Positive test for tuberculosis during screening 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).
8. 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.
9. Positive for hepatitis C antibody.
10. Known history of HIV or positive HIV test at screening.
11. 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
12. 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
13. 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.
14. 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.
15. 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.
16. Currently receiving or had treatment within 12 months prior to screening with T-cell depleting agents (eg, antithymocyte globulin, Campath).
17. Currently receiving of had treatment with an interleukin 2 (IL-2) based therapy (eg, Proleukin).
18. 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 3months prior to screening; other biologics within < 5 drug half lives prior to screening.
19. Participants who have received intraarticular, intralesional, or intramuscular corticosteroids within 2 weeks prior to screening or intravenous corticosteroids within 6 weeks prior to screening.
20. 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 6weeks after the end of treatment period in the study.
21. Currently receiving treatment in another investigational device or drug study.
22. 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.

Related Information

• Primary Sponsor: Kimura Takeshi
• Secondary ID(s): NCT04680637