E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transfusion-dependent beta thalassemia with myocardial iron overload |
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E.1.1.1 | Medical condition in easily understood language |
Increased amount of iron in the heart muscle (iron overload) as a result of blood transfusions |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
E.1.2 | Term | Blood and lymphatic system disorders |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy on cardiac iron as measured by cardiac T2* MRI in patients with transfusion-dependent beta thalassemia |
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E.2.2 | Secondary objectives of the trial |
•Safety and tolerability in patients with transfusion-dependent beta thalassemia
•Proportion of patients who demonstrate an improvement in cardiac T2* MRI
•Hemoglobin level
•Volume of blood transfused
•Hepatic iron levels as measured by T2* MRI
•Total serum iron
•Immunogenicity (anti-drug antibodies)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic/Pharmacodynamic (PK/PD) Sub-study
An optional 168-hour PK/PD substudy will be conducted for patients who consent and/or assent. Additional blood samples for PK analysis
will be collected in a subset of patients at the following time points relative to the third week (Week 3) dose in Group B, and the third week
(Week 29) dose in Group A. Blood samples will be collected at Hour 0, and postdose Hours 0.5, 2, 4, 8, 24, 48, 72, and 168 (prior to next dose).
In Group A, blood samples at Hours 72 and 168 will be collected prior to the next dose of study drug. Immunogenicity and PK samples at Week 4
in Group B and Week 30 in Group A may coincide with samples collected for the PK/PD substudy. |
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E.3 | Principal inclusion criteria |
1. Patients ≥ 14 years of age with transfusion-dependent beta thalassemia and must have been transfused within 1 month of randomisation.
2. Two separate MRIs that both demonstrate cardiac T2* MRI from 6 to 35 msec (≥ 6 to ≤ 35 msec) with no more than a 15% difference between the first (MRI 1) and second (MRI 2) reading. MRI 1 and MRI 2
must be at least 3 weeks apart. MRI 1 may be a historical SOC cardiac
T2* MRI performed within 12 months of randomisation.
3. Patients must be receiving iron chelation therapy for a minimum of 1 year and be on a stable, appropriate dose of iron chelation therapy for a minimum of 8 weeks prior to randomisation and expected to remain stable during study participation.
4. Female patients must be of non-childbearing potential, or using a highly effective method of contraception during participation in the study and for 30 days after the last dose of study drug. 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.
5. Female patients of childbearing potential must have a negative serum pregnancy test at Screening, negative pregnancy test predose on the first day study drug is administered, and negative pregnancy tests during the study.
6. Male patients must be surgically sterile, or using a highly effective method of contraception during participation in the study and for 30 days after the last dose of study drug. 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.
7. Patient must be willing and able to provide written informed consent and/or assent. Parent(s) or legal guardian(s) to patients younger than the local age of majority (ie, adult) is willing and able to provide
informed consent and assist the patient in complying with all protocol requirements. |
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E.4 | Principal 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, inhaled steroid medications, and nonsteroidal anti-inflammatory drugs) or have a planned surgery (excluding dental surgery or simple dermatologic procedures).
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 and ECG findings, 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, clinically significant arrhythmias, 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. Patients with known hepatitis B, hepatitis C who are being treated for a positive viral load or are noncompliant with their hepatitis medication.
8. Known and active human immunodeficiency virus (HIV) infection.
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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The mean change from baseline (Screening) in cardiac iron level as measured by T2* MRI (comparing 26 weeks of SOC to 26 weeks of SOC and LJPC-401 [Group A versus Group B]). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Mean change from baseline in cardiac iron level as measured by cardiac T2* MRI at week 52
2. Mean change in hepatic iron level as measured by cardiac T2* MRI.
3. Mean change in total serum iron
4. Mean change in haemoglobin
5. Change in the volume of blood transfused
6. The proportion of patients with an increase of at least 10% compared to baseline (Screening) in the T2* level as measured by cardiac MRI.
7. The proportion of patients with an increase of at least 20% at Week 52 compared to baseline (Screening) in the T2* level as measured by cardiac MRI |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Immediate treatment versus delayed treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Cyprus |
Greece |
Italy |
Lebanon |
Thailand |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |