A multi-center clinical study to determine the effects of LJPC-401 on iron in the heart muscle in patients with beta-thalassemia who are treated with routine blood transfusions

Phase 1

• Conditions: Transfusion-dependent beta thalassemia with myocardial iron overload; MedDRA version: 20.0Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-003372-31-IT
• Lead Sponsor: A JOLLA PHARMACEUTICAL COMPANY

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-07
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Patients = 18 years of age with transfusion-dependent beta thalassemia and must have been transfused within 1 month of randomization.
2. Patients must have a TSAT = 50% at Screening.
3. Two separate cardiac MRIs should be greater than 3 weeks but no more than 3 months apart that both demonstrate cardiac T2* MRI of 6 to 35 (msec) with no more than a 10% difference between the first and second reading.
4. Patients must be receiving iron chelation therapy for a minimum of 1 year and be on a stable dose of maximally tolerated iron chelation therapy for a minimum of 8 weeks prior to study and expected to remain stable during study.
5. Female patients must be of non-childbearing potential, or using a highly effective method of contraception during participation in the study. Highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate when used consistently and correctly. These include: surgical sterility (vasectomy, bilateral tubal ligation, or hysterectomy); hormonal intrauterine device (IUD); hormonal intrauterine system (IUS), implants, or injections; consistent use of an approved oral contraceptive pill (combined progestin/estrogen pill or progestin-only pill); combined intravaginal or transdermal method; and abstinence.
6. Female patients of childbearing potential must have a negative serum pregnancy test at Screening, and negative urine pregnancy test at Week 1 (ie, prior to initial dosing of study drug).
7. Male patients must be surgically sterile, or using a highly effective method of contraception during participation in the study. Highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate when used consistently and correctly.
8. Patient must be willing and able to provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
2. Pregnant or lactating women.
3. Patients taking an immunosuppressive agent (excluding topical over-the-counter steroids) or have a planned surgery (excluding dental surgery or simple dermatologic procedures) during participation in this study or within 2 weeks prior to randomization.
4. Patients participating in an unapproved investigational drug or investigational therapeutic device study within 30 days prior to randomization, ie, there must be at least 30 days in between the last dose on a prior study and randomization on this trial.
5. Patients with a concomitant disease, disability or condition, including laboratory abnormality, 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 in this study, including, but not limited to, alcohol dependency or abuse, drug dependency or abuse, or psychiatric disease.
6. Patients who are unwilling or unable to comply with the study protocol requirements.
7. Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
8. Patients with Child Pugh class C cirrhosis or liver failure.
9. Patients with severe congestive heart failure (New York Heart Association [NYHA] = Class 4).
10. Use of erythropoiesis stimulating agents in the past 3 months prior to study entry.
11. History of allergic reaction to hepcidin or excipients.
12. Contraindication to MRI scanning.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy on cardiac iron as measured by cardiac T2* MRI in adult patients with transfusion-dependent beta thalassemia.<br>;Secondary Objective: ¿Safety and tolerability in adult patients with transfusion-dependent beta thalassemia <br>¿TSAT <br>¿Immunogenicity (anti-LJPC-401 antibodies)<br>;Primary end point(s): The mean change from baseline (Screening) in intrapatient cardiac iron level as measured by T2* MRI at week 26.;Timepoint(s) of evaluation of this end point: Week 26 (comparing 26 weeks of Standard of Care (SOC) [Group A] to 26 weeks of SOC plus LJPC-401 [Group B]).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Mean change from baseline (Screening) in intrapatient cardiac iron level as measured by cardiac T2* MRI at week 52<br>2. Mean change from baseline (Screening) in intrapatient cardiac iron level as measured by cardiac T2* MRI at post-baseline visits other than<br>Week 26 and Week 52.<br>3. Change in time-weighted TSAT%.<br>4. The proportion of patients with an increase of at least 20% compared to baseline (Screening) in the T2* level as measured by cardiac MRI.;Timepoint(s) of evaluation of this end point: Week 52 (comparing delayed treatment/Group A [26 weeks of SOC followed by 26 weeks of SOC plus LJPC-401] to 52 weeks of immediate treatment/Group B [SOC + LJPC 401]).