A Study With LJPC-401 for the Treatment of Myocardial Iron Overload in Patients With Transfusion-Dependent Beta Thalassemia

Study Overview
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Brief Summary
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This study is a Phase 2 multicenter, randomized, open-label, parallel-group study. The primary objective of the study is to evaluate the effect of LJPC-401 (synthetic human hepcidin) on iron levels in patients with transfusion-dependent beta thalassemia with myocardial iron overload.

Official Title
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A Multi-Center, Randomized, Open-Label, Parallel-Group Study With LJPC-401 for the Treatment of Myocardial Iron Overload in Patients With Transfusion-Dependent Beta Thalassemia

Conditions
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Beta-Thalassemia

Intervention / Treatment
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* Drug: LJPC-401
* Drug: LJPC-401


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 14 years of age with transfusion-dependent beta thalassemia. Patients must have increased iron levels in the heart as measured by magnetic resonance imaging (MRI). Two separate cardiac T2*MRI from 6 to 35 msec; <= 15% difference between the two. Patients must be receiving iron chelation therapy for a minimum of 1 year and be on a stable dose prior to study and expected to remain stable during study. Female patients of childbearing potential must not be pregnant, must have negative pregnancy tests, and must use an effective birth control method during the study. Male patients must be either surgically sterile or use an effective birth control method during the study. Patient must be willing and able to provide written informed consent. Parent of legal guardian to patients younger than age of majority must be willing and able to provide informed consent. Exclusion Criteria: Any significant medical condition or lab abnormality that would prevent the patient from participating in the study. Pregnant or lactating women. Patients taking an immunosuppressive agent (except topical over-the-counter steroids, inhaled steroid medications, and non-steroidal anti-inflammatory drugs) or have a planned surgery (except dental surgery or simple dermatologic procedures). Patients participating in an unapproved investigational clinical trial within 30 days of this study. Patients with a disease, disability or condition which may interfere with the conduct of the study, or which would, in the opinion of the Investigator, pose an unacceptable risk to the patient. Patients who are unwilling or unable to comply with the study requirements. Patients with known hepatitis B or hepatitis C, or being treated for a positive viral load or are noncompliant with hepatitis medications. Known and active human immunodeficiency virus (HIV) infection. Patients with Child Pugh class C cirrhosis or liver failure. Patients with severe congestive heart failure (NYHA Class 4). Use of erythropoiesis stimulating agents in the past 3 months prior to study entry. History of allergic reaction to hepcidin or excipients. Contraindication to MRI scanning.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A - Delayed therapy<br>standard chelation therapy alone for 26 weeks followed by standard chelation therapy plus LJPC-401 for 26 weeks | Drug: LJPC-401<br>* subcutaneous injection, up to 20 mg per week from week 26 to 52<br>* Other names: synthetic human hepcidin;|
| Active Comparator: Group B - Immediate therapy<br>standard chelation therapy plus LJPC-401 for 52 weeks | Drug: LJPC-401<br>* subcutaneous injection, up to 20 mg per week from week 1 to 52<br>* Other names: synthetic human hepcidin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of LJPC-401 on cardiac iron | Change in cardiac T2* magnetic resonance imaging (MRI) | 26 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of LJPC-401 on cardiac iron | Change in cardiac T2*MRI | 52 Weeks | 
| Effect of LJPC-401 on hepatic iron | Change in hepatic T2*MRI | 52 Weeks | 
| Effect of LJPC-401 on serum iron | Mean change in serum iron | 56 Weeks | 
| Effect of LJPC-401 on hemoglobin | Mean change in hemoglobin | 52 Weeks | 
| Effect of LJPC-401 on volume of blood transfused | Change in transfused blood volume | 56 Weeks | 
| Effect of LJPC-401 on its potential to elicit an immune response | Measured by blood laboratory tests and the presence of anti-drug antibodies | 56 Weeks | 
| Effect of LJPC-401 on the incidence of treatment-emergent adverse events |  | 56 Weeks | 
| Effect of LJPC-401 on vital signs-heart rate |  | 56 Weeks | 
| Effect of LJPC-401 on vital signs-body temperature |  | 56 Weeks | 
| Effect of LJPC-401 on vital signs-respiratory rate |  | 56 Weeks | 
| Effect of LJPC-401 on vital signs-blood pressure |  | 56 Weeks | 
| Effect of LJPC-401 on body weight | Change in body weight (kilograms) | 56 Weeks |