E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transfusion-dependent beta thalassemia with myocardial iron overload |
|
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 |
|
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 |
|
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 adult patients with transfusion-dependent beta thalassemia |
|
E.2.2 | Secondary objectives of the trial |
Safety and tolerability in adult patients with transfusion-dependent beta
thalassemia
Hemoglobin level
Volume of blood transfused
Intrapatient hepatic iron levels as measured by T2* MRI
Total serum iron
Immunogenicity (anti-drug antibodies) |
|
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 (PK) Sub-study
An optional PK substudy will be performed in a subset of subjects who
provide a separate informed consent (approximately 20).
Blood sampling for PK sub-study will be taken for patients in Group A
receiving 5 mg of IMP on Week 27 and for patients in Group B on Week
3, before the IMP injection at Hour -24, Hour 0, and post-dose at Hours
0.5, 2, 4, 8, 12 (optional), 24, 48, and 168 (pre-dose before next weekly
dosing). Hour 0 and Hour 168 can be combined with the immunogenicity
and PK sample collected at visits on Week 27 and Week 28 for Group A
and Week 3 and Week 4 for Group B. |
|
E.3 | Principal inclusion criteria |
1. Patients ≥ 18 years of age with transfusion-dependent beta thalassemia and must have been transfused within 1 month of randomization.
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 randomization.
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 study and expected to remain stable during
study.
4. Female patients must be of nonchildbearing 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, and a negative urine pregnancy test
predose on the first day study drug is administered.
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. |
|
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 overthe-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, 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. Patients with known hepatitis B or 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 Child Pugh class C cirrhosis or liver failure.
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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The mean change from baseline (Screening) in intrapatient cardiac iron level as measured by T2* MRI at week 26 |
|
E.5.1.1 | 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]). |
|
E.5.2 | Secondary end point(s) |
• Mean change from baseline in intrapatient cardiac iron level as
measured by cardiac T2* MRI at Week 52
• Mean change in intrapatient hepatic iron levels as measured by T2*
MRI
• Mean change in total serum iron
• Mean change in hemoglobin
• Change in the volume of blood transfused
• The proportion of patients with an increase of at least 20% at Week 26
compared to baseline (Screening) in the T2* level as measured by
cardiac MRI |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 |
|
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 |
|
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | 9 |
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 |