Safety and efficacy of hCDR1 (Edratide) in patients with active systemic lupus erythematosus: results of phase II study

Abstract

Objective: To evaluate the safety and efficacy of hCDR1 (Edratide) in patients with systemic lupus erythematosus (SLE).

Methods: Patients (n=340) with SLE ≥4 ACR criteria (4-11, mean 7) with active disease (SLEDAI-2K of 6-12). Patients were on average 7.1 years post-diagnosis and their organ involvement was mainly musculoskeletal, mucocutaneous and haematologic. Placebo or Edratide was administered subcutaneously weekly at doses of 0.5, 1.0 or 2.5 mg. The co-primary endpoints were SLEDAI-2K SLE Disease Activity and Adjusted Mean SLEDAI (AMS) reduction in patients compared with controls using a landmark analysis. Secondary outcomes were improvement in British Isles Lupus Assessment Group (BILAG) Responder Index and medicinal flare analysis.

Results: Edratide was safe and well tolerated. The primary endpoints based solely on SLEDAI-2K and AMS were not met. The secondary predefined endpoint, BILAG, was met for the 0.5 mg Edratide arm in the intention to treat (ITT) cohort (N=316) (OR=2.09, p=0.03) with trends in the 1.0 and 2.5 mg doses. There was also a positive trend in the Composite SLE Responder Index of the ITT cohort. Post hoc analysis showed that the BILAG secondary endpoint was also met for the 0.5 mg Edratide for a number of subgroup dose levels, including low or no steroids, seropositivity and patients with 2 grade BILAG improvement.

Conclusions: The favourable safety profile and encouraging clinically significant effects noted in some of the endpoints support the need for additional longer term Edratide studies that incorporate recent advances in the understanding and treatment of SLE, including steroid treatment algorithms, and using a composite primary endpoint which is likely to include BILAG.

Trial registration number: NCT00203151.

Keywords: Autoimmune Diseases; Systemic Lupus Erythematosus; Treatment.

Figure 1

Patient distribution over the course of the study.

Figure 2

Disease activity as measured by British Isles Lupus Assessment Group (BILAG) responder analysis in different groups. (A) BILAG responder analysis at Last Office Visit (LOV) versus Baseline predefined analysis on intention to treat (ITT) cohort (0.5 mg arm n=76; Placebo arm n-83). (B) BILAG responder analysis of patients receiving steroids <20 mg/day at baseline (0.5 mg arm n=68; Placebo arm n=69). (C) BILAG responder analysis of seropositive patients (anti-DNA>30 IU at baseline) (0.5 mg arm n=26; Placebo arm n=31).

Figure 3

Medicinal flare analysis on intention to treat (ITT) cohort.

Figure 4

Composite systemic lupus erythematosus (SLE) Responder Index (cSRI) on intention to treat (ITT) cohort.