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A single-arm study to evaluate the efficacy and safety of a single dose of ferric carboxymaltose injection (Feinject intravenous injection 500 mg) in hemodialysis patients with iron deficiency anemia (FCM HD Trial)

Evaluation study of ferric carboxymaltose injection in hemodialysis patients (FCM HD Trial)

30

The median age was 68.5 years (range 45.0-96.0 ), comprising 17 men and 13 women. The median BMI was 22.45 kg/m^2. At enrollment, the median hemoglobin (Hb) was 9.4 g/dL (range 8.3-9.9 g/dL), the median serum ferritin was 57.0 ng/mL (range 7.0-476.0 ng/mL), and the median transferrin saturation (TSAT) was 18.0% (range 4.4-62.4%). The distribution of sex and age at enrollment were as expected, and these background data are consistent with iron deficiency anemia.

Because the pace of enrollment was slower than initially expected, it was deemed difficult to achieve the target number of cases under the current circumstances. Consequently, the number of participating facilities was increased from March 2024. Thereafter, enrollment numbers began to rise, with the 30th case registered on May 16, 2024, and the observation period for the final registered patient concluded on August 13, 2024. Regarding patient enrollment, 9 patients were registered at Kinokawa Clinic and 8 at Fujii Hospital, meaning these two facilities alone accounted for over half of the total. All other facilities registered five or fewer patients, and three facilities registered none. A total of 30 patients completed the protocol, comprising all enrolled cases.

One patient experienced dialysis AV fistula occlusion. We determined that it was unrelated to the administration of Ferric carboxymaltose 500mg. No other adverse events were observed.

Study Patients In this analysis, for dependent variables with multiple time series data, a mixed-effects model was used to determine whether there were statistically significant differences in the changes from baseline at each time point. The significance level was set at p < 0.05. <Primary Endpoint> A total of 30 patients were analyzed. For the primary endpoint, the change in hemoglobin (Hb) from baseline to Week 4 demonstrated a significant increase of 0.50 g/dL (95% CI: 0.24, 0.76; p < 0.001). <Secondary Endpoints> Hemoglobin From baseline to Week 4, Hb increased significantly by 0.50 g/dL (95% CI: 0.24, 0.76; p < 0.001). At Week 8, the increase was 0.72 g/dL (95% CI: 0.46, 0.99; p < 0.001). At Week 12, the increase was 0.70 g/dL (95% CI: 0.44, 0.96; p < 0.001). Iron-Related Markers Because serum ferritin and TSAT showed marked skewness from a normal distribution, they were log-transformed. After log-transformation, the skewness was eliminated, so the analysis used the transformed values. The log-transformed results were as follows: Ferritin (Log(Ferritin)): A significant increase was observed at all time points (Weeks 1, 2, 4, 8, and 12) relative to baseline. TSAT (Log(TSAT)): A significant increase was observed at Weeks 1, 2, 4, and 8, but no significant difference was noted at Week 12 compared to baseline. Quality of Life (QOL) Measures EQ-5D-5L: No significant differences were observed at any point throughout the study. SF-36: Of the measured dimensions, "Vitality" and "Mental Health" showed significant increases at Weeks 4, 8, and 12 compared with baseline. "Role-Physical" showed a significant decrease only at Week 8 compared with baseline. "General Health" showed a significant increase only at Week 4 compared with baseline. Subscales: "Mental Component Summary Score 1" and "Mental Component Summary Score 3" demonstrated significant increases at Weeks 4, 8, and 12 compared with baseline. "Physical Component Summary Score 3" showed a significant decrease only at Week 8 compared with baseline <Safety Endpoints> A single 500 mg intravenous dose of ferric carboxymaltose was well-tolerated in this study population. Among the 30 patients, only 1 adverse event (AE) was reported: shunt occlusion. This occurrence rate is considered within the range expected in hemodialysis patients. Serum Ferritin During the treatment period, 16 patients (53.3%) had serum ferritin levels >= 500 ng/mL at least once. However, by Week 8, ferritin levels had fallen below 500 ng/mL in all but one patient. This single patient had already had serum ferritin >= 500 ng/mL before starting treatment. TSAT During the treatment period, 2 patients (6.7%) had TSAT >= 50% at least once. Two weeks later, TSAT fell below 50% in all patients except for the one who already presented high TSAT at baseline. Serum 8-OHdG Compared with baseline, serum 8-OHdG showed a significant increase at Week 1 (0.07 [95% CI: 0.04-0.10]; p < 0.001) and at Week 2 (0.04 [95% CI: 0.01-0.07]; p < 0.010). At Weeks 4, 8, and 12, no significant differences were observed compared with baseline. Serum Hepcidin Compared with baseline, serum hepcidin increased significantly at Week 1 (34.09 ug/L [95% CI: 22.07-46.11]; p < 0.001), Week 2 (21.07ug/L [95% CI: 9.05-33.09]; p < 0.001), and Week 4 (20.72 ug/L [95% CI: 8.70-32.74]; p < 0.001). No significant differences were observed at Weeks 8 and 12 compared with baseline. Serum intact-FGF23 At Week 1, the change from baseline in intact-FGF23 was 513.70 pg/mL (95% CI: 91.68-935.73; p = 0.018), indicating a significant increase. No significant changes were observed at Weeks 2, 4, 8, and 12 compared with baseline. Serum Phosphate No statistically significant changes were observed at Weeks 1, 2, 4, 8, or 12 compared with baseline. Because serum hepcidin and serum intact-FGF23 showed marked skewness from a normal distribution, log-transformation was performed. After log-transformation, the distribution of intact-FGF23 showed no severe skewness, whereas the log-transformed serum hepcidin values did not approximate a normal distribution but the skewness was reduced. Analyses were therefore performed using the log-transformed values. The results of the log-transformed analysis were as follows: Serum Hepcidin (Log(serum Hepcidin)): Significant increases at all time points (Weeks 1, 2, 4, 8, and 12) compared with baseline. Serum intact-FGF23 (Log(serum intact-FGF23)): A significant increase only at Week 1 compared with baseline; no significant changes were observed at Weeks 2, 4, 8, or 12.

Overall, single-dose intravenous ferric carboxymaltose (FCM) safely and effectively raised Hb levels in this cohort of hemodialysis patients with iron deficiency, with transient increases in ferritin, TSAT, hepcidin and serum 8-OhdG level.

June. 13, 2025

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs051230025

Araki Shin-ichi

Wakayama Medical University Hospital

811-1 Kimiidera, Wakayama City,Wakayama, Japan

wfcm2023@wakayama-med.ac.jp

Tanaka Yusuke

Wakayama Medical University Hospital

811-1 Kimiidera, Wakayama City,Wakayama, Japan

+81-73-441-0639

wfcm2023@wakayama-med.ac.jp

Complete

May. 23, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Japanese patients who are 18 years of age or older at the time of informed consent
2) Maintained HD patients with HD history of 12 weeks or more who receive HD 3 times a week
3) Patients with iron deficiency anemia with Hb <10 g/dL and TSAT <20% or serum ferritin <100 ng/mL
4) Patients who are undergoing treatment for renal anemia with ESA or HIF-PH inhibitors and have not changed the dosage and administration since 4 weeks before the enrollment date
5) Patients who understand the contents of this study and can obtain written consent to participate in this study from themselves

1) Patients who fall under any of the following regarding blood transfusion
a.Those who received a blood transfusion within 8 weeks before the registration date
b.Those who are scheduled to undergo surgery requiring blood transfusion during the study period
2) Patients who are known or suspected to correspond to any of the following
a.Those with active bleeding such as gastrointestinal bleeding
b.Those with iron deficiency anemia due to blood loss other than HD
3) Patients with uncontrolled co-morbidities that may affect the safety of the study subject or the validity of the study results
4) Female patients who are pregnant or breastfeeding
5) Patients who are allergic to FCM
6) Patients weighing less than 25 kg (dry weight) within 1 month prior to enrollment
7) Patients who have had a malignancy within the past 5 years from the date of enrollment
8) Patients who have used study drug within 30 days prior to enrollment date
9) Patients who fall under any of the following regarding hospitalization
a. Those who are hospitalized at the time of registration
b. Those who are scheduled to be hospitalized during the study period
10) Patients with obvious pulmonary congestion on chest x-ray

Both

Iron deficiency anemia

Evaluation of efficacy and safety for 84 days after administration of ferric carboxymaltose to study subjects.

Change in Hb level at 4 weeks after administration of FCM

Change in hemoglobin (Hb) Level
Change in serum ferritin level
Change in Transferrin Saturation (TSAT)
Change in QOL values in EQ-5D-5L
Change in QOL value in SF-36

+81-73-441-0896

Feb. 21, 2023

None