High Dose IV Iron Plus ESA in Chemotherapy-induced Anemia

Prospective, Multicenter, Randomized Phase 3 Trial of High Dose IV Iron in Combination of Erythrocytosis Stimulating Agents in Chemotherapy Induced Anemia With Functional Iron Deficiency

This study is a multicenter, prospective, randomized phase 3 clinical study comparing the efficacy and safety of the combination treatment of ESA and high-dose IV iron (darbepoietin alfa + ferric derisomaltose/iron isomaltoside) with ESA monotherapy (darbepoietin alfa alone) in CIA patients with functional iron deficiency.

Study Overview

• Status: Recruiting
• Conditions: Anemia
• Intervention / Treatment: Drug: Ferric Derisomaltose Injection; Drug: Darbepoetin Alfa Injection

• Study Type: Interventional
• Enrollment (Anticipated): 312
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dae Young Zang, Ph.D.; Phone Number: +82-31-380-3704; Email: fhdzang@gmail.com

Study Locations

• Korea, Republic of
  • Anyang-si, Korea, Republic of
    • Recruiting
    • Hallym University Medical Center
    • Contact: Dae Young Zang; Phone Number: +82-31-380-3704; Email: fhdzang@hallym.or.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient who has signed a written consent

  • Age ≥ 19 ③ Histologically diagnosed advanced/metastatic solid cancer

    • Patients who have received myelosuppressive chemotherapy for palliative purposes within 1 month of participating in the study and plan to proceed with chemotherapy while participating in this study

    • Anemia with functional iron deficiency

      1. Hemoglobin <10g/dL

      2. functional iron deficiency: transferrin saturation <50% AND serum ferritin 30-800ng/mL ⑤ ECOG performance status 0-2 ⑥ life expectancy ≥ 24weeks

         Exclusion Criteria:

• Absolute iron deficiency (serum ferritin <30 ng/mL AND transferrin saturation <20%) or no iron deficiency (serum ferritin ≥800 ng/mL OR transferrin saturation ≥50%)

  • If there is another cause of anemia other than chemotherapy-induced anemia (eg, vitamin B12 or folic acid deficiency, hemolytic anemia, myelodysplastic syndrome, etc.)

    • Ongoing bleeding at the time of study registration

      • Patients who require rapid blood transfusion at the time of study registration (eg, rapidly progressing anemia)

        • Presence of bone marrow tumor invasion

          • Receiving erythropoiesis stimulating agents within 3 weeks of study registration or have a history of oral or intravenous iron administration or blood transfusion within 2 weeks of study registration

            • History of venous thromboembolism within 6 months or taking anticoagulants at the time of study registration

              • Past or family history of hemochromatosis ⑨ History of hypersensitivity to iron treatment or erythropoiesis stimulating agents ⑩ Uncontrolled acute or chronic infection ⑪ Renal dysfunction (serum creatinine ≥2.0 mg/dL, or glomerular filtration rate <30 mL/min/1.73 m2) or liver dysfuction (AST or ALT 3 times or more the upper limit of normal) ⑫ Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose IV iron plus ESA combination arm	Drug: Ferric Derisomaltose Injection; Ferric derisomaltose/iron isomaltoside (as iron) (0 weeks): 20mg/kg, diluted in 250ml of 0.9% physiological saline and injected intravenously over 30-60 minutes; Drug: Darbepoetin Alfa Injection; Darbepoietin alfa (0 weeks, 3 weeks, 6 weeks, 9 weeks): 6.75㎍/kg, subcutaneous or intravenous administration
Active Comparator: ESA monotherapy arm	Drug: Darbepoetin Alfa Injection; Darbepoietin alfa (0 weeks, 3 weeks, 6 weeks, 9 weeks): 6.75㎍/kg, subcutaneous or intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Hb change	Mean change in Hb concentration from baseline to 12 weeks	from baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin response	defined as an increase in Hb level of 2.0g/dL≥ from baseline value during 12-week study period	during 12-week study period
Time to hemoglobin response		during 12-week study period
Proportion of patients requiring RBC transfusion during 12-week study period		during 12-week study period
Quality of life assessment by Functional Assessment of Cancer Therapy-Anemia (FACT-An)/health-related quality of life instrument with 8 items (HINT-8)/EQ-5D-5L		during 12-week study period
Safety analysis	Adverse events including AE of special interst (Anaphylaxis, Infusion reaction, Thromboembolic event)	during 12-week study period

Collaborators and Investigators

• Sponsor: Hallym University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: HIGHEST-CIA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No