E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The principle research objective of CLI 00076 includes, as a primary way of measuring efficacy, the average hemoglobin consumption following the transfusion of INTERCEPT treated RBCs vs. conventional RBCs will be assessed.
Safety will be primarily evaluated with the assessment of antibody formation that are specific to INTERCEPT-treated RBCs. |
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E.2.2 | Secondary objectives of the trial |
•Adverse events •Transfusion reactions within 24 hours of a study transfusion with the assigned study product •Frequency of allo immunization to RBC allo-antigens
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age ≥11 years, of either gender. •Female subjects will be either: Non-childbearing potential or Childbearing potential. Women of childbearing potential must have negative serum or urine pregnancy tests prior to study treatment to rule out pregnancy. Females of childbearing potential must be willing to consent to using methods of birth control which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomized partner •Diagnosed with thalassemia major and currently participating in a chronic transfusion program •At least a one year history of chronic RBC transfusion support with a stable transfusion requirement (per treating physician) •Intervals of at least 14 days between RBC transfusions •All RBC components are given on one day for each transfusion episode •Signed and dated informed consent form •Pediatric assent is granted (when required by local regulations)
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E.4 | Principal exclusion criteria |
•Baseline serum/plasma sample with antibody specific to INTERCEPT treated RBCs (positive RBC screening test) •Evidence of splenic hyperfunction defined as a transfusion requirement >180 mL/kg/year (at 100% hematocrit) •Splenic enlargement: spleen palpable ≥4 cm below costal margin OR ≥18 cm in longitudinal diameter by ultrasound (chosen at the Investigator’s discretion according to the data available with ultrasound data being preferable) •Any subject for whom a substantial change in the number of RBC components transfused is anticipated within 12 months of study entry due to anticipated splenectomy or other change in clinical status •Subjects at high risk of cardiac decompensation (e.g., subjects with a documented left ventricle ejection fraction <56%, or with a multislice multiecho T2* cardiac magnetic resonance <10 ms) •Alloimmunization to high frequency blood group antigens to the extent that the provision of compatible blood may not be feasible for the study (alloimmunization alone is not an automatic exclusion) •Current specialized treatment with washed or frozen RBC •Requirement for gamma irradiated RBC components (would present blinding difficulty due to blood component labeling regulations) •Subject with G-6PD deficiency requiring treatment with medications that are known to adversely affect RBC viability (see Appendix D) •Positive DAT based on the defined algorithm for evaluation as defined below (and presented in Section 7.3.1.): oA poly-DAT reaction strength >2+ oPan-reactivity of subject plasma/serum sample with a CE marked commercial IAT antibody screening panel (e.g., ID-DiaCell panel, with or without papain) that precludes the identification of underlying allo-antibodies or indicates the presence of auto-antibody •Documented active HIV infection (defined as RNA positive) •Documented active HCV infection (defined as RNA positive) and currently treated with concomitant medications known to suppress the bone marrow function •Pregnant or breast feeding females •Currently receiving chemotherapy for treatment of cancer •Acute or chronic medical disorder other than thalassemia that, in the opinion of the investigator or medical monitor, may prevent the subject from completing participation in the study •If in the Investigator’s opinion the subject cannot comply with the protocol, they may be deemed ineligible •Participation in another clinical study, either concurrently or within the previous 28 days
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoint: Hemoglobin (Hgb)consumption during each efficacy evaluation period is measured as the hemoglobin mass transfused per subject adjusted for episode-specific body weight and duration (adjusted Hgb consumption units are Hgb g/kg body weight/day).
Primary Safety Endpoint: Incidence of a treatment-emergent antibody with confirmed specificity to INTERCEPT treated RBCs associated with clinically significant hemolysis
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The efficacy endpoint is the mean consumption of hemoglobin normalized for subject body weight and time. For each efficacy evaluation period, this endpoint is calculated by averaging the adjusted amount of hemoglobin transfused across the four episodes. Adjustments are made by dividing the hemoglobin transfused by the episode-specific subject-body-weight and duration (results are in units of Hgb g/kg body weight/day).
The safety endpoint is assessed for all subjects following all transfusions of study RBC components during each treatment period (including wash-in and efficacy evaluation transfusions). |
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E.5.2 | Secondary end point(s) |
•Adverse events •Transfusion reactions within 24 hours of a study transfusion with the assigned study product •Frequency of allo immunization to RBC allo-antigens
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From the time after informed consent is administered through the End-of-Study Visit.
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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) | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 |
Conventional RBC Components (not treated with investigational product) |
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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
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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 | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 30 |