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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-004894-29 | EudraCT Number |
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| Name | Class |
|---|---|
| ADIR, a Servier Group company | INDUSTRY |
| Les Laboratoires Servier (L.L.S), Russia | INDUSTRY |
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The purpose of this study is to compare the pharmacokinetics (PK) of both lyophilized and liquid S95014 formulations during the induction phase after a single IV dose in newly diagnosed paediatric patients with ALL
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| S95014 lyophilizate | Experimental | Lyophilized S95014 reconstituted will provide 5 mL of extractable volume with the concentration of 750 U/mL. The vial of lyophilized powder (3.750 U/vial) is reconstituted with 5.2 mL of Sterile Water for Injection to obtain a 750 U/mL solution for single use. |
|
| S95014 liquid | Active Comparator | Liquid S95014 is provided as 3.750 U per 5 mL solution in a single use vial to obtain a 750 U/mL solution for single use. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lyophilized S95014 | Drug | Lyophilized S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics Measurement | Area Under the Plasma Asparaginase activity - Time curve from Time zero to infinity (AUCinf) | Predose up to 600 hours |
| Pharmacokinetics Measurement | Maximum observed plasma asparaginase activity (Cmax) | Predose up to 600 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics Measurements | Observed Plasma Asparaginase Activity 14 days post-dose (Cday 14) of S95014 | 14 days post-dose |
| Activity Measurement | Plasma Asparaginase Activity (PAA) of ≥ 0.1 U/mL after the administration of either liquid or lyophilized S95014. |
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Inclusion Criteria:
Non-inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alexander Isaakovich Karachunskiy, PhD | Director of Institute of Oncology, Radiology and Nuclear Medicine. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Regional Children Clinical Hospital | Chelyabinsk | 454087 | Russia | |||
| Children Regional Clinical Hospital |
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| Label | URL |
|---|---|
| Find results on Servier Clinical Trial Data website | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| Individual Participant Data Set | View IPD |
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.
Access can be requested for all interventional clinical studies:
In addition, access can be requested for all interventional clinical studies in patients:
After Marketing Authorisation in EEA or US if the study is used for the approval.
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
There was a sceening period (from Day-14 to Day-1) to check the eligibility of the patient in the study
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| ID | Title | Description |
|---|---|---|
| FG000 | S95014 Lyophilizate | Lyophilized S95014 reconstituted will provide 5 mL of extractable volume with the concentration of 750 U/mL. The vial of lyophilized powder (3.750 U/vial) is reconstituted with 5.2 mL of Sterile Water for Injection to obtain a 750 U/mL solution for single use. Lyophilized S95014: Lyophilized S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 2, 2020 | May 16, 2023 |
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| Liquid S95014 | Drug | Liquid S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. |
|
| Day 7, 14, 18 and 25 post-dose of either liquid or lyophilized S95014 |
| Immunogenicity Measurements | Anti-drug antibodies (ADA) formation against S95014 and anti-PEG with the lyophilized or liquid formulations (positive patients). | Pre-dose, post-dose (sum of 14 and 25 days post-dose) |
| Krasnodar |
| 350007 |
| Russia |
| Russian Children Clinical Hospital | Moscow | 119571 | Russia |
| Regional Children Hospital | Nizhny Novgorod | 603136 | Russia |
| V.A. Almazov National Medical Research Center | Saint Petersburg | 197341 | Russia |
| Regional Children Clinical Hospital | Yekaterinburg | 620149 | Russia |
| Study Protocol | View IPD |
| Statistical Analysis Plan | View IPD |
| Informed Consent Form | View IPD |
| Clinical Study Report | View IPD |
| Study-level clinical trial data | View IPD |
| FG001 | S95014 Liquid | Liquid S95014 is provided as 3.750 U per 5 mL solution in a single use vial to obtain a 750 U/mL solution for single use. Liquid S95014: Liquid S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. |
| COMPLETED |
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| NOT COMPLETED |
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One patient in the S95014 liquid (LIQ) group was prematurely withdrawn from the study on the day of randomization due to a major deviation/protocol violation (patient with B-cell Burkitt Acute Lymphoblastic Leukemia) and did not receive the study treatment. Another patient who was randomized in the lyophilizate (LYO) group but received the LIQ formulation in error, was analyzed according to the treatment actually received, LIQ, and counted here under LIQ.
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| ID | Title | Description |
|---|---|---|
| BG000 | S95014 Lyophilizate | Lyophilized S95014 reconstituted will provide 5 mL of extractable volume with the concentration of 750 U/mL. The vial of lyophilized powder (3.750 U/vial) is reconstituted with 5.2 mL of Sterile Water for Injection to obtain a 750 U/mL solution for single use. Lyophilized S95014: Lyophilized S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. |
| BG001 | S95014 Liquid | Liquid S95014 is provided as 3.750 U per 5 mL solution in a single use vial to obtain a 750 U/mL solution for single use. Liquid S95014: Liquid S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacokinetics Measurement | Area Under the Plasma Asparaginase activity - Time curve from Time zero to infinity (AUCinf) | The Pharmacokinetic (PK) Analysis Set included the patients who have received at least one dose of IMP and are evaluable for PK analysis : the patients who had enough samples collected to provide interpretable PK results with no deviations that might have affected the PK interpretation (e.g. infusion interrupted for any reason, deviation in the theoretical administered dose > 10%, at least one missing PK sample during the 48 first hours, ≥ 2 missing PK samples after the 48-hour time point). | Posted | Geometric Mean | Geometric Coefficient of Variation | mU*day/mL | Predose up to 600 hours |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics Measurement | Maximum observed plasma asparaginase activity (Cmax) | The Pharmacokinetic (PK) Analysis Set included the patients who have received at least one dose of IMP and are evaluable for PK analysis : the patients who had enough samples collected to provide interpretable PK results with no deviations that might have affected the PK interpretation (e.g. infusion interrupted for any reason, deviation in the theoretical administered dose > 10%, at least one missing PK sample during the 48 first hours, ≥ 2 missing PK samples after the 48-hour time point). | Posted | Geometric Mean | Geometric Coefficient of Variation | mU/mL | Predose up to 600 hours |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics Measurements | Observed Plasma Asparaginase Activity 14 days post-dose (Cday 14) of S95014 | The PKAS included the patients who have received at least one dose of IMP and are evaluable for PK analysis : the patients who had enough samples collected to provide interpretable PK results with no deviations that might have affected the PK interpretation . Cday-14 could not be calculated in one patient (in S95014 liquid group) who had only 3 positive values exceeding the Lower Limit of Quantification | Posted | Geometric Mean | Geometric Coefficient of Variation | mU/mL | 14 days post-dose |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Activity Measurement | Plasma Asparaginase Activity (PAA) of ≥ 0.1 U/mL after the administration of either liquid or lyophilized S95014. | The analysis on the Plasma Asparaginase Actvity was performed on the Safety Set analysis, defined as the set of all patients who had received at least one dose of S95014 in the study. | Posted | Count of Participants | Participants | No | Day 7, 14, 18 and 25 post-dose of either liquid or lyophilized S95014 |
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| Secondary | Immunogenicity Measurements | Anti-drug antibodies (ADA) formation against S95014 and anti-PEG with the lyophilized or liquid formulations (positive patients). | The immunogenicity analyses were carried out in the Immunogenicity Analysis Set (IAS) which includes all patients who had received at least one dose of IMP and had at least one post-dose sample evaluable for immunogenicity testing. | Posted | Count of Participants | Participants | Pre-dose, post-dose (sum of 14 and 25 days post-dose) |
|
The period of time over which adverse event data were collected was1,5 month.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | S95014 Lyophilizate | Lyophilized S95014 reconstituted will provide 5 mL of extractable volume with the concentration of 750 U/mL. The vial of lyophilized powder (3.750 U/vial) is reconstituted with 5.2 mL of Sterile Water for Injection to obtain a 750 U/mL solution for single use. Lyophilized S95014: Lyophilized S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. | 1 | 43 | 19 | 43 | 43 | 43 |
| EG001 | S95014 Liquid | Liquid S95014 is provided as 3.750 U per 5 mL solution in a single use vial to obtain a 750 U/mL solution for single use. Liquid S95014: Liquid S95014 will be intravenously administered over 1 hour at the dose of 2500 U/m2 at Day 3 of the induction phase. Patients will receive other backbone chemotherapy agents as per ALL-MB 2015 protocol. | 2 | 45 | 18 | 45 | 45 | 45 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hypofibrinogenemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Antithrombin III decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Blood fibrinogen decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| ALT increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| AST increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Protein S decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Neutropenic colitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Edematous pancreatitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Enterocolitis hemorrhagic | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Candida pneumonia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Gastroenteritis norovirus | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Gastrointestinal bacterial infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Pseudomembranous colitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Catheter site thrombosis | General disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Brain stem stroke | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Posterior reversible encephalopathy syndrome | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Tonic convulsion | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hyperbilirubinemia | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hepatosplenomegaly | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hepatotoxicity | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Post procedural hemorrhage | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
| |
| Superior vena cava syndrome | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Pelvic Venous Thrombosis | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood fibrinogen decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Antithrombin III decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Protein S decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Toxic neuropathy | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Ammonia increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Neutropenic colitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hypofibrinogenemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Hyperbilirubinemia | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
| |
| International normalized ratio increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Hemoglobin decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area in Oncology | Institut de Recherches Internationales Servier | +33155724366 | clinicaltrials@servier.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 23, 2022 | May 16, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
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| >=65 years |
|
| Male |
|
| Asian |
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| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Anti-S95014 Positive / Anti-PEG Negative |
|