E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Lymphoblastic Leukemia |
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E.1.1.1 | Medical condition in easily understood language |
Acute Lymphoblastic Leukemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Phase 1: To assess the safety and tolerability of a single dose of SHP674 in Japanese participants (dose confirmation) in the tolerability assessment period of Part 1.
Phase 2: To assess the safety, pharmacokinetics and efficacy of SHP674 dose in Part 2 (found to be tolerated in Part 1) in the treatment of newly diagnosed untreated acute lymphoblastic leukemia (ALL) in Japanese participants. |
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E.2.2 | Secondary objectives of the trial |
Part 1: – To assess the percentage of subjects with newly diagnosed,untreated ALL who have a plasma asparaginase activity of ≥0.1 IU/mL 14 days (336 hours) after the first dose of SHP674. – To assess the safety of SHP674. – To assess the PK of SHP674. – To assess the immunogenicity of SHP674. – To assess the survival rate at 1 year after the start of study treatment. – To assess the event-free survival rate at 1 year after the start of study treatment. Part 2: – To assess the safety of SHP674 – To assess the PK of SHP674. – To assess the immunogenicity of SHP674. – To assess the survival rate at 1 year after the start of study treatment. – To assess the event-free survival rate at 1 year after the start of study treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 1 to ≤21 years at the time of informed consent; • Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2; • Newly diagnosed, untreated precursor B-cell ALL • No prior therapy for malignant tumor such as chemotherapy and radiation therapy before signing the informed consent; • Life expectancy of at least 6 months from the date of enrollment;
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E.4 | Principal exclusion criteria |
• Mature B-cell ALL ; Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL • Preexisting known coagulopathy ; • History of pancreatitis; • Continuous use of corticosteroids; • Prior treatment or possible prior treatment with an L-asparaginase preparation; • History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs; • Pregnant
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: –Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period
Part 2: –Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: – Incidence of TEAEs and Drug-related TEAEs: Enrollment up to 5 weeks Part 2: –Plasma asparaginase activity :14 days after the first dose of SHP674 |
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E.5.2 | Secondary end point(s) |
–Incidence and Nature of TEAEs and Drug-related TEAEs. –Parts 1 and 2: Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) and Anti-Polyethylene Glycol (PEG) Antibody. –Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674. –Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL. –Survival Rate at 1 Year After the Start of Study Treatment. –Event-free Survival Rate at 1 Year After the Start of Study Treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Incidence of TEAEs and Drug-related TEAEs: Part 1 and 2: Up to 1 year • Laboratory values, Vital signs, PK parameters, Survival rate, and Event-free survival rate at 1 year after the start of study treatment • Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) and Anti-Polyethylene Glycol (PEG) Antibody : Part 1: Predose and 25 days post dose; Part 2: Predose and 25 days post dose • Plasma asparaginase activity :Part 1:14 days after the first dose of SHP674; Part 2: Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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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End of Trial is defined as the last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
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 | 4 |