Comparison of Octaplas LG and Octaplas SD
Conditions
Keywords
Octaplas LG, Octaplas SD
Brief summary
The primary objective of the study was to compare the efficacy of Octaplas LG with Octaplas SD in terms of recovery of coagulation factors and other haemostatic parameters. The secondary objective of the study was to compare the safety and tolerability of Octaplas LG with Octaplas SD in terms of haematological and clinical chemistry parameters and adverse event monitoring.
Interventions
BIOLOGICALOctaplas LG
Octaplas LG was composed of human coagulation-active plasma treated with solvent/detergent for 1-1.5 hours to remove enveloped viruses, eg, HIV, HBV, and HCV. An additional manufacturing step, involving an affinity ligand gel, removed prion proteins. Octaplas LG was provided frozen in pyrogen free plastic bags.
BIOLOGICALOctaplas SD
Octaplas SD was composed of human coagulation-active plasma treated with solvent/detergent for 4-4.5 hours to remove enveloped viruses, eg, HIV, HBV, and HCV. Octaplas SD was provided frozen in pyrogen free plastic bags.
Sponsors
Octapharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Capable of understanding and complying with all aspects of the protocol. * Signed Informed Consent. * Capable of understanding the plasmapheresis information sheet and sign it. * Healthy male or female volunteers, age 18 years or older. * Women must have negative pregnancy test (human chorionic gonadotropin \[HCG\] based assay). * Women must have sufficient methods of contraception (eg, intrauterine device, oral contraception, etc). * No clinically relevant abnormalities in medical history and general physical examination. * Standard health insurance.
Exclusion criteria
* Pregnancy or lactation. * Tattoos within the last 3 months. * Subject was treated therapeutically with fresh frozen plasma, blood, or plasma-derived products within the last 6 months. * Hypersensitivity to blood products or plasma proteins. * History of angioedema. * History of coagulation or bleeding disorder or any other known abnormality affecting coagulation, fibrinolysis, or platelet function. * Any clinically significant abnormal laboratory values. * IgA deficiency. * Seropositivity for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus type 1 or type 2 antibodies. * Symptoms of a clinically relevant illness within 3 weeks before the first trial day. * History of or suspected drug or alcohol abuse. * Subjects currently participating in another clinical study. * Any investigational medicinal product administration within the last 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | From 5 minutes after the end of plasmapheresis up to 2 hours after the end of study drug administration | Recovery was defined as the maximum percentage change of the coagulation factor value measured 5 minutes after the end of plasmapheresis to the coagulation factor value measured at 15 minutes or 2 hours after the end of study drug administration. The coagulation parameters were measured by validated assays from blood samples obtained 5 minutes after the end of plasmapheresis and 15 minutes and 2 hours after the end of study drug administration. |
| Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | From 5 minutes after the end of plasmapheresis up to 2 hours after the end of study drug administration | Recovery was defined as the maximum (minimum for activated partial thromboplastin time) percentage change of the haemostatic parameter value measured 5 minutes after the end of plasmapheresis to the haemostatic parameter value measured at 15 minutes or 2 hours after the end of study drug administration. The haemostatic parameters were measured by validated assays from blood samples obtained 5 minutes after the end of plasmapheresis and 15 minutes and 2 hours after the end of study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Plasmin Inhibitor | From 30 minutes before plasmapheresis up to 24 hours after the end of plasmapheresis | Values of plasmin inhibitor were measured by validated assays from blood samples obtained 30 minutes before plasmapheresis, 5 minutes after the end of plasmapheresis, 15 minutes and 2 hours after the end of study drug administration, and 24 hours and 7 days after initiation of plasmapheresis. The concentration of plasmin inhibitor is reported as the percentage of plasmin inhibition. A higher concentration of plasmin inhibitor results in a higher percentage of plasmin inhibition. |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants received 1200 mL of Octaplas LG intravenously once and 1200 mL of Octaplas SD intravenously once in a crossover design. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Enrolled in Study and Randomized | Adverse Event | 0 | 1 |
| Enrolled in Study and Randomized | Reason not Specified | 1 | 0 |
| Enrolled in Study and Randomized | Withdrawn by the Investigator | 0 | 1 |
| First Intervention | Adverse Event | 1 | 4 |
| First Intervention | Reason not Specified | 0 | 1 |
| First Intervention | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 32.6 Years STANDARD_DEVIATION 9.11 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 60 | 39 / 60 |
| serious Total, serious adverse events | 1 / 60 | 0 / 60 |
Outcome results
Primary
Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI
Recovery was defined as the maximum percentage change of the coagulation factor value measured 5 minutes after the end of plasmapheresis to the coagulation factor value measured at 15 minutes or 2 hours after the end of study drug administration. The coagulation parameters were measured by validated assays from blood samples obtained 5 minutes after the end of plasmapheresis and 15 minutes and 2 hours after the end of study drug administration.
Time frame: From 5 minutes after the end of plasmapheresis up to 2 hours after the end of study drug administration
Population: Per protocol population: All participants who had evaluable efficacy measurements in both of the treatment periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor I | 8.11 Percentage change | Standard Deviation 8.93 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor VIII | 1.50 Percentage change | Standard Deviation 9.38 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor V | 6.31 Percentage change | Standard Deviation 9.35 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor IX | 8.86 Percentage change | Standard Deviation 9.11 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor II | 7.08 Percentage change | Standard Deviation 6.46 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor X | 7.90 Percentage change | Standard Deviation 8.96 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor VII | 8.48 Percentage change | Standard Deviation 11.03 |
| Octaplas LG | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor XI | 6.53 Percentage change | Standard Deviation 6.32 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor XI | 8.24 Percentage change | Standard Deviation 7.54 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor I | 9.12 Percentage change | Standard Deviation 8.75 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor II | 6.68 Percentage change | Standard Deviation 7.35 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor V | 6.91 Percentage change | Standard Deviation 10.09 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor VII | 9.28 Percentage change | Standard Deviation 14.53 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor VIII | 5.21 Percentage change | Standard Deviation 9.93 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor IX | 11.08 Percentage change | Standard Deviation 7.74 |
| Octaplas SD | Recovery of the Coagulation Factors I, II, V, VII, VIII, IX, X, and XI | Factor X | 9.97 Percentage change | Standard Deviation 12.37 |
Primary
Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C
Recovery was defined as the maximum (minimum for activated partial thromboplastin time) percentage change of the haemostatic parameter value measured 5 minutes after the end of plasmapheresis to the haemostatic parameter value measured at 15 minutes or 2 hours after the end of study drug administration. The haemostatic parameters were measured by validated assays from blood samples obtained 5 minutes after the end of plasmapheresis and 15 minutes and 2 hours after the end of study drug administration.
Time frame: From 5 minutes after the end of plasmapheresis up to 2 hours after the end of study drug administration
Population: Per protocol population: All participants who had evaluable efficacy measurements in both of the treatment periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Octaplas LG | Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | Prothrombin time | 1.36 Percentage change | Standard Deviation 4.71 |
| Octaplas LG | Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | Activated partial thromboplastin time | -4.60 Percentage change | Standard Deviation 3.71 |
| Octaplas LG | Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | Protein C | 9.49 Percentage change | Standard Deviation 8.44 |
| Octaplas SD | Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | Prothrombin time | 2.85 Percentage change | Standard Deviation 6.18 |
| Octaplas SD | Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | Activated partial thromboplastin time | -5.73 Percentage change | Standard Deviation 4.39 |
| Octaplas SD | Recovery of the Haemostatic Parameters Prothrombin Time, Activated Partial Thromboplastin Time, and Protein C | Protein C | 9.75 Percentage change | Standard Deviation 6.97 |
Secondary
Concentration of Plasmin Inhibitor
Values of plasmin inhibitor were measured by validated assays from blood samples obtained 30 minutes before plasmapheresis, 5 minutes after the end of plasmapheresis, 15 minutes and 2 hours after the end of study drug administration, and 24 hours and 7 days after initiation of plasmapheresis. The concentration of plasmin inhibitor is reported as the percentage of plasmin inhibition. A higher concentration of plasmin inhibitor results in a higher percentage of plasmin inhibition.
Time frame: From 30 minutes before plasmapheresis up to 24 hours after the end of plasmapheresis
Population: Per protocol population: All participants who had evaluable efficacy measurements in both of the treatment periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Octaplas LG | Concentration of Plasmin Inhibitor | Post-plasmapheresis 7 days | 90.95 Percentage inhibition | Standard Deviation 9.79 |
| Octaplas LG | Concentration of Plasmin Inhibitor | Pre-plasmapheresis 30 minutes | 90.51 Percentage inhibition | Standard Deviation 9.93 |
| Octaplas LG | Concentration of Plasmin Inhibitor | Post-plasmapheresis 5 minutes | 85.72 Percentage inhibition | Standard Deviation 9.34 |
| Octaplas LG | Concentration of Plasmin Inhibitor | Post-transfusion 15 minutes | 79.81 Percentage inhibition | Standard Deviation 8.15 |
| Octaplas LG | Concentration of Plasmin Inhibitor | Post-transfusion 2 hours | 79.21 Percentage inhibition | Standard Deviation 8.45 |
| Octaplas LG | Concentration of Plasmin Inhibitor | Post-plasmapheresis 24 hours | 88.35 Percentage inhibition | Standard Deviation 9.41 |
| Octaplas SD | Concentration of Plasmin Inhibitor | Post-transfusion 2 hours | 75.23 Percentage inhibition | Standard Deviation 9.11 |
| Octaplas SD | Concentration of Plasmin Inhibitor | Post-plasmapheresis 7 days | 91.65 Percentage inhibition | Standard Deviation 9.88 |
| Octaplas SD | Concentration of Plasmin Inhibitor | Post-transfusion 15 minutes | 74.93 Percentage inhibition | Standard Deviation 8.72 |
| Octaplas SD | Concentration of Plasmin Inhibitor | Pre-plasmapheresis 30 minutes | 91.53 Percentage inhibition | Standard Deviation 9.12 |
| Octaplas SD | Concentration of Plasmin Inhibitor | Post-plasmapheresis 24 hours | 85.40 Percentage inhibition | Standard Deviation 8.93 |
| Octaplas SD | Concentration of Plasmin Inhibitor | Post-plasmapheresis 5 minutes | 85.67 Percentage inhibition | Standard Deviation 10.08 |