MO800EFFICACY AND SAFETY OF CINACALCET IN CHINESE MAINTAINANCE HEMODIALYSIS PATIENTS WITH DIFFERENT STAGES OF SECONDARY HYPERPARATHYROIDISM: RESULTS OF ACTIVE STUDY
Authors: Study Group Active 
Published: May 2021

Abstract

Background and Aims
Secondary hyperparathyroidism (SHPT), as a common complication in advanced chronic kidney disease (CKD) has become a global public health problem. Published literatures showed higher risk of bone fracture, cardiovascular events and all-cause mortality was associated with uncontrolled SHPT in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce intact parathyroid hormone (iPTH) levels in patients with SHPT. However, there is no large-cohort study and stratified analysis of cinacalcet based on the level of iPTH in China. The ACTIVE study was designed to test the efficacy and safety of cinacalcet in treating Chinese maintenance hemodialysis patients with mild-to-severe SHPT, as well as to investigate the benefit of long-term, continuous medication with cinacalcet in the real-world setting.

Method
ACTIVE study was a phase IV, open-label, multicenter clinical trial including two phases: Phase 1 was a cohort study with 32 weeks’ follow-up. Phase 2 was a real-world study of 20 additional weeks in which patients who completed the cohort study decided independently whether to continue taking cinacalcet at their own cost. Eligible maintenance hemodialysis (MHD) patients with baseline iPTH ≥300 pg/mL from April 2017 to September 2019 in 23 centers in China were treated with cinacalcet orally. Patients were grouped based on their iPTH level as mild (300-600 pg/mL), moderate (600-900 pg/mL) or severe (≥900 pg/mL) SHPT.

Results
911 patients were screened and of 750 eligible patients, 275 were identified as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT. The number of people who completed all 52-week follow-up in the mild, moderate and severe SHPT groups were 184 (66.91%), 164 (73.21%), and 166 (66.14%), respectively(Fig 1). The baseline and interim analysis results was published on 2020 EDTA. The number of patients achieving iPTH target (150-300 pg/mL) was 85 (31.02%) in mild group, 56 (25.00%) in moderate group and 27 (10.76%) patients in severe group at 20-week visit, and the proportion of patients achieving iPTH target was 33.94% (n=93), 24.11% (n=54) and 13.55% (n=34) at 32-week visit. The trends of the proportion of patients achieving iPTH target increased in all 3 different groups (Fig 2). The number of patients who reached both targets of serum calcium (Ca2+) and serum phosphorus (P) in the mild, moderate and severe SHPT group was 61 (22.26%), 42 (18.75%), 37 (14.74%) at 20-week visit, and 44 (16.06%), 34 (15.18%), 41 (16.33%) at 32-week visit, respectively. At the end of the 20th and the 32nd week of treatment, serum Ca2+×P and fibroblast growth factor-23 (FGF-23) decreased significantly compared with their baseline values (Table 1). In the extension 32-52 weeks study, the corresponding proportion of patients who achieved iPTH target in the three SHPT groups was 11.41%, 6.06%, and 4.81%, respectively. The safety analysis showed the most common treatment-related AE were hypocalcemia, hyperlipidemia and loss of appetite. This study is sponsored by Kyowa Kirin China Pharmaceutical Co., Ltd.

Conclusion
Oral cinacalcet HCl was effective and safe in reducing iPTH in patients receiving HD with mild-to-severe SHPT.