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A Phase 1b/2, Double-Blind, Placebo-Controlled, Randomized, Parallel-Arm Study to Explore the Safety, Pharmacokinetics, and Proof of Biological Activity of DS-7011a in Patients with Systemic Lupus Erythematosus

Phase 1b/2 Study of DS-7011a in Patients with Systemic Lupus Erythematosus (SLE)

26

The mean age of participants was 49.7 (Standard deviation [SD] 13.05, the DS-7011a group was 51.1 years [SD 13.80] and the placebo group was 45.2 years [SD 9.99]), there was 1 male in the DS-7011a group, and all other participants were female. Most of the participants in the DS-7011a group identified as White (15 [78.9%] participants), and Black or African American and Asian (2 [10.5%] participants each). The majority (18 [94.7%] participants) of the DS-7011a group participants identified as not Hispanic or Latino. The placebo group had 4 (66.7%) participants who identified as Asian, and 2 (33.3%) participants who identified as Black or African American. All 6 (100%) placebo participants identified as not Hispanic or Latino. During enrolment, the "current disease severity" in the DS-7011a group was 13 (68.4%) participants with moderate severity and 4 (21.1%) with mild severity, and in the placebo group was 4 (66.7%) participants with moderate severity and 2 (33.3%) participants with mild severity.

A total of 36 patients were enrolled in this study and a total of 26 participants were randomized, and 1 participant in the placebo group withdrew consent. A total of 25 participants were included in modified intent-to-treat (mITT) and safety analysis sets; 19 participants in the DS-7011a group and 6 participants in the placebo group. 19 participants in the DS-7011a group were included in pharmacokinetic analysis set. 17 participants in the DS-7011a group completed study treatment and 16 participants completed the study, 5 participants in the placebo group completed the study treatment and the study.

Overall, 31 treatment-emergent AEs (TEAEs) were reported by 15 (60.0%) participants (11 [57.9%] participants in DS-7011a group and 4 [66.9%] participants in placebo group). The type, incidence, and severity of TEAEs were generally comparable between the treatment groups. No severe TEAEs or deaths were reported during this study. No participants in the DS-7011a group had an serious adverse event (SAE). One participant in placebo group experienced a SAE of "Systemic lupus erythematosus" of moderate severity and was discontinued from the study due to exacerbation of the symptoms. A total of 6 (24.0%) participants reported 6 treatment-emergent adverse events of special interest (AESIs) (COVID-19, influenza, and upper respiratory tract infection, each for 1 participant in the DS-7011a group, and pneumonia, influenza A virus test positive, and rhinorrhea, each for 1 participant in the placebo group); the proportion of participants reporting AESIs was higher in the placebo group compared with DS-7011a group (50.0% vs 15.8%). One mild AESI of "upper respiratory tract infection" from the DS-7011a group was considered related to the study treatment by the investigator.

The collected data for safety and tolerability as Primary Outcome measure was reported in the Adverse events section. Efficacy Results: All efficacy analyses were based on the mITT Analysis Set. The DS-7011a group had improvement of SLE symptoms compared with the placebo group results, as indicated by the overall decrease in scores of Cutaneous Lupus Area and Severity Index Activity (CLASI-A), Cutaneous Lupus Activity Investigator Global Assessment (CLA-IGA), SLE Disease Activity Index 2000 (SLEDAI-2K), and Physician's Global Assessment Systemic Lupus Erythematosus (PGA-SLE), at all visits (Weeks 4, 8, 12, and 16) compared to baseline. Additionally, there was an improvement in Clinician's Global Impression of Change (CGI-C) score for DS-7011a group compared with placebo group at Week 16; a higher proportion of participants in DS-7011a group versus placebo were rated to have "very much improved" (35.3% vs 0), "much improved" (17.6% vs 0) or "minimally improved" (29.4% vs 0) changes in SLE severity from baseline. Pharmacokinetic (PK) results: DS-7011a exhibited PK properties characteristic of an IgG1 monoclonal antibody including a half-life of 19 days.

The type, incidence, and severity of TEAEs were generally comparable between the treatment groups. No severe TEAEs or deaths were reported during this study. The DS-7011a group had improvement of SLE symptoms compared with the placebo group results, as indicated by several endpoints indicative of clinical efficacy. DS-7011a exhibited PK properties characteristic of an IgG1 monoclonal antibody.

Yes

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Information: -Study Protocol -Statistical Analysis Plan (SAP) -Informed Consent Form (ICF) Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230588

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Complete

May. 01, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Male and female subjects must be of 18 years or more with definite SLE for at least 6 months prior to Screening, defined according to the 2019 European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) classification criteria for SLE3, including documented history of positivity for antinuclear antibody (titer >=1:80).
- Body mass index (BMI) >=18 kg/m^2 and body weight >=45 kg.
- Presence of active CLE (acute, subacute, and chronic cutaneous lupus) with active skin involvement and a CLASI-A score of 4 or higher at the time of Screening and randomization, as recognized by 2 adjudicators, despite adequate use of conventional therapies (either topical corticosteroids or antimalarial agents used for at least 12 weeks prior to Screening) or because of the requirement to discontinue these therapies due to side effects or poor tolerability.
- Subjects must be willing to have skin tape harvests collected from the affected skin area (skin tape stripping done on the target lesion).
- Subjects must be vaccinated against COVID-19.

- Active LN on induction therapy, or induction therapy completed within 12 weeks prior to Screening.
- Active neuropsychiatric SLE.
- Primary diagnosis of autoimmune or rheumatic disease other than SLE or drug-induced lupus.
- History of chronic, recurrent or recent serious infection, including viral infections, as determined by the investigator, or requiring anti-infective treatment within 12 weeks prior to Screening.
- History of severe herpes infection or signs of herpes or varicella zoster viral infection within 12 weeks prior to Screening.
- Positive COVID-19 molecular (polymerase chain reaction [PCR]) test at Screening or symptoms suggestive of SARS-CoV-2 infection or close contact with an individual with SARS-CoV-2 infection within 2 weeks prior to randomization.

Both

Systemic Lupus Erythematosus (SLE)

20 mg/kg, Intravenous infusions every 4 weeks (Weeks 0, 4, and 8)

safety and tolerability

pharmacokinetics, efficacy and immunogenicity properties

+81-52-691-7151

Feb. 26, 2024

United States/Macedonia/China