Zoledronic Acid Treatment in Patients With Congenital Dyserythropoietic Anemia

Zoledronic Acid Treatment in Patients With Congenital Dyserythropoietic Anemia: An Exploratory Study

Background:

Congenital Dyserythropoietic Anemia (CDA) is a group of rare hereditary blood disorders characterized by ineffective erythropoiesis, leading to chronic anemia and organ damage. Current treatment options are very limited, mainly relying on regular blood transfusions, which can cause severe complications over time. Our laboratory research and animal models suggest that Zoledronic acid, a medication commonly used for bone health, may improve ineffective erythropoiesis.

Purpose:

The purpose of this exploratory study is to evaluate the efficacy and safety of Zoledronic acid in adult patients with CDA who do not have other effective treatment options. The primary goal is to see if this treatment can increase hemoglobin levels and reduce the need for blood transfusions.

Study Design:

This is a prospective, single-center, single-arm study. Participants will receive an initial intravenous dose (4 mg) of Zoledronic acid. After a 4-week observation period to ensure safety, participants will receive additional doses every 4 weeks for a total of 4 doses. Researchers will monitor hemoglobin levels, transfusion frequency, spleen size, and overall quality of life over a period of 12 to 24 weeks.

Study Overview

• Status: Recruiting
• Conditions: Congenital Dyserythropoietic Anemia (CDA)
• Intervention / Treatment: Drug: zoledronic acid

• Study Type: Interventional
• Enrollment (Estimated): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xin Zhao, MD; Phone Number: 8613702041366; Email: zhaoxin@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital
    • Contact: Xin Zhao, MD; Phone Number: 8613702041366; Email: zhaoxin@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years, regardless of gender.
• Diagnosis of Congenital Dyserythropoietic Anemia (CDA) based on clinical presentation, laboratory tests, and family investigation, with the presence of RBM28 mutation and/or increased vacuolization within nucleated red blood cells under light microscopy of bone marrow.
• Presence of anemia (Hemoglobin < 100 g/L at screening) or transfusion dependence (defined as an average transfusion interval of < 8 weeks within the past 3 months).
• Performance status is acceptable (ECOG score 0-2).
• Normal renal function (estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73m²).
• Serum calcium levels within the normal range.
• Female patients of childbearing potential must have a negative pregnancy test before enrollment and agree to use effective contraception during the study and for 3 months after completion.
• The patient and/or guardian voluntarily sign the informed consent form.

Exclusion Criteria:

• Known hypersensitivity to bisphosphonates or any of their excipients.
• Severe periodontal disease or a recent history (within 6 months) of osteonecrosis of the jaw.
• Hypocalcemia.
• Pregnant or lactating women.
• Currently receiving other experimental drug treatments that may affect erythropoiesis (e.g., Luspatercept).
• Active, uncontrolled systemic infection.
• Severe cardiac, pulmonary, or hepatic dysfunction, as judged by the investigator to be unsuitable for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Zoledronic Acid; Participants in this arm will receive a total of 4 doses of Zoledronic acid. Following the first dose, there is a 4-week safety observation period before proceeding with subsequent doses every 4 weeks. The total follow-up period for efficacy and safety assessment is 24 weeks.

Drug: zoledronic acid; Zoledronic acid will be administered at a dose of 4 mg via a standardized intravenous (IV) infusion lasting no less than 15 minutes. To ensure safety, the initial dose is followed by a 4-week rigorous observation period. If the treatment is well-tolerated without significant adverse events, subsequent doses will be given every 28 days for a total of 4 cycles. Patients will be closely monitored for serum calcium levels and renal function (eGFR) throughout the intervention period to mitigate potential risks associated with bisphosphonate therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin Level From Baseline	The primary endpoint is the hematologic response achieved by participants at 12 weeks after the first dose of Zoledronic acid. Response includes: 1) Complete Response (CR): Hemoglobin ≥ 120 g/L; 2) Partial Response (PR): Not meeting CR criteria, but achieving independence from red blood cell transfusions OR an increase in HGB of ≥ 20 g/L from baseline.	12 weeks after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin Level at 4 Weeks	Assessment of the increase in peripheral blood hemoglobin concentration from baseline to 4 weeks after the first dose	4 weeks after the first dose
Change in Red Blood Cell Transfusion Interval	Comparison of the time interval between red blood cell transfusions before and after Zoledronic acid treatment	Up to 24 weeks
Change in Spleen Size	Assessment of the change in spleen size measured by ultrasound compared to baseline	Up to 24 weeks
Change in Quality of Life Assessed by the 36-Item Short Form Health Survey (SF-36)	Assessment of the change in patient quality of life compared to baseline. It is measured using the 36-Item Short Form Health Survey (SF-36). The score ranges from 0 to 100, where a higher score indicates a better quality of life.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2026
• Primary Completion (Estimated): February 25, 2027
• Study Completion (Estimated): August 12, 2027

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Zoledronic Acid; Congenital Dyserythropoietic Anemia
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Dyserythropoietic, Congenital; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Organophosphorus Compounds; Organophosphonates; Diphosphonates; Zoledronic Acid
• Other Study ID Numbers: IIT2025152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to the extremely small sample size (1-2 cases) and the rare nature of the disease, individual participant data will not be shared to protect patient privacy and confidentiality.

Drug and device information, study documents

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