E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with beta-thalassemia major who are eligible for a haploidentical HSCT |
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E.1.1.1 | Medical condition in easily understood language |
Patients with beta-thalassemia major who are eligible for a stem cell transplantation from a related haploidentical donor |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054661 |
E.1.2 | Term | Thalassemia major |
E.1.2 | System Organ Class | 100000004850 |
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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 |
The objective of the study is to evaluate the safety and feasibility of ATIR201 in patients with beta-thalassemia major who received a T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). Safety and tolerability will be primarily evaluated by the occurrence of acute graft-versus- host disease (GVHD) grade III/IV within 180 days post HSCT. Efficacy will be primarily evaluated by transfusion-free survival (TFS), occurrence of severe infections, and time to T-cell reconstitution, taking into account hematologic and sustained engraftment.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient Inclusion Criteria: • Confirmed diagnosis of beta-thalassemia major: - Hypertransfusion program with eight or more red blood cell (RBC) transfusions a year and a confirmed annual transfusion of ≥ 100 ml/kg/year. - Genotype consistent with clinical diagnosis of beta-thalassemia major (including hemoglobin E-beta-thalassemia genotype) - Iron chelation therapy initiated, or not yet initiated but at risk of transfusional iron overload • Lansky / Karnofsky performance score > 70% • Eligible for haploidentical stem cell transplantation according to the investigator taking into account the feasibility of transplanting patients with pre-existing antibodies (e.g. anti-A, anti-B, and/or other anti-donor red cell antibodies or known presence of HLA antibodies against the non-shared donor haplotype) • Male or female, age ≥ 2 years and ≤ 25 years
Donor Inclusion Criteria:
• Haploidentical family donor with at least 4 out of 8 or 5 out of 10 matches at the HLA- A, -B , -C, -DR, and/or DQ loci as determined by high resolution typing • Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for donors under the age of 18 will be followed) • Eligible for donations of human blood and blood components according to local requirements and regulations • Fit to receive granulocyte colony-stimulating factor (G-CSF) and to give peripheral blood stem cells (blood counts and blood pressure within standards) • Eligible for donation according to the transplantation center |
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E.4 | Principal exclusion criteria |
Exclusion Criteria Patient:
• Availability of a fully matched related or unrelated donor following a donor search, which might have been initiated before screening. • Patient assigned to Pesaro risk class 3 • Symptomatic cardiac failure: left ventricular ejection fraction at rest < 50% and no improvement with exercise, or shortening fraction < 26% (evaluated by echocardiogram or MUGA) • Hepatic failure: > 5 times the upper limit of normal range (ULN) for age of AST or > 2.5 times the ULN for age of total serum bilirubin • Renal function (creatinine clearance or GFR) < 50% of the lower limit of normal (LLN) for age • Symptomatic pulmonary failure: DLCO, FEV1, or FEC (diffusion capacity) < 50% of predicted (corrected for hemoglobin); if unable to perform a pulmonary function test, oxygen saturation < 85% on room air • Positive pregnancy test (females of childbearing age only) • Positive test for HIV-1 or HIV-2 • Active viral, bacterial, fungal, or parasitic infection, including hepatitis B, hepatitis C • Prior HSCT for beta-thalassemia major • Known allergy to any of the components of ATIR201 (e.g., dimethyl sulfoxide) • Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study
Donor Exclusion Criteria:
• Positive pregnancy test or nursing (females of childbearing age only) • Positive viral test for HIV-1, HIV-2, HBV, HCV, or Treponema pallidum • Hemoglobin S ≥ 50%, or presence of beta-thalassemia intermedia • History of congestive heart failure, unstable angina, or history of stroke |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of acute graft versus host disease (GvHD) grade III/IV within 180 days post HSCT. |
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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) |
Secondary safety endpoints: • Occurrence of acute and chronic GVHD (all grades/severities) • Occurrence of graft rejection • Occurrence of prolonged donor red cell aplasia • Donor chimerism
Secondary efficacy endpoints: • Transfusion-free survival (TFS) • Occurrence of severe (NCI grade 3-5) infections • Time to T-cell reconstitution, defined as the time to CD3+ > 0.2×10E9/l in peripheral blood (at two consecutive measurements; time to first measurement) • Overall survival (OS), defined as the time from HSCT until death from any cause • Transplant-related mortality (TRM), defined as death due to causes other than disease recurrence |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 12 months post HSCT |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The end of the study is defined as the date at which the last data point from the last patient is received. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |