E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immune Thrombocytopenia |
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E.1.1.1 | Medical condition in easily understood language |
autoimmune disease in which platelets (a type of blood cell involved in
clotting) are destroyed, leading to bruising. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021245 |
E.1.2 | Term | Idiopathic thrombocytopenic purpura |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 |
To evaluate the safety and tolerability of i.v. administered SM101 at various dose levels in a single/multiple dosing manner in subjects with chronic ITP |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of SM101 following single and multiple
intravenous dosing in the treatment of subjects with chronic ITP
•To evaluate an appropriate SM101 dose for the additional dose
escalation included in the extension part and for future clinical trials
with SM101
•To evaluate various immunology parameters during and after SM101
treatment
•To evaluate pharmacokinetic (PK) parameters of i.v. administered
SM101 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has provided written informed consent prior to any study-related procedure
2. Male or female subjects aged 18 to 75, with or without splenectomy
3. Diagnosis of persistent or chronic adult Primary Immune thrombocytopenia (ITP) based on subject’s history, physical examination, blood count and blood film examination according to the international consensus report guidelines with at least 3 months ITP history
4. Subjects > 60 years of age at the timepoint of ITP diagnosis must have had a documented history of chronic ITP with a bone marrow report to confirm the diagnosis
5. Subject has previously received at least one ITP therapy
6. All other previously completed ITP treatment must achieve at least 5time their terminal half-life prior to first administration of IMP
7. Concurrent ITP corticosteroid dose, if any, has been stable for 4 weeks preceding the first dose of IMP, and is intended to remain stable during the IMP treatment period
8. Platelet count less than 30,000/μL from at least 2 measurements within 4 weeks prior to first investigational medicinal product (IMP) administration. The second measurement should not be older than 1 week. Both measurements should be at least 1 week apart.
9. Patients with a body weight ≤ 100kg
10. Adequate liver and kidney function (as detailed in the protocol)
11. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1, with a life expectancy of at least 6 months
12. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 1 week prior to first IMP administration
13. Both WOCBP and men must use a medically acceptable method of contraception (Appendix III) prior to inclusion and throughout the study
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E.4 | Principal exclusion criteria |
1. Female subjects who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period
2. Secondary thrombocytopenia caused by: previously diagnosed or possible high risk of conditions that may be associated with autoimmune thrombocytopenia, liver diseases, drugs, bone marrow diseases, recent transfusions, inherited thrombocytopenia, etc.
3. Subjects with confirmed HIV, hepatitis B or C infection.
4. Subjects with other acute infections within 4 weeks preceding the first dose of investigational medicinal product (IMP)
5. Subject received intravenous immunoglobulins (IVIGs) or anti-D antibody treatment within 4 weeks preceding the first dose of IMP
6. Subject received rituximab or any other B-cell depleting agent within 24 months preceding the first dose of IMP
7. Subject receives concomitant ITP medication other than corticosteroids, except rescue medication during the clinical trial
8. Splenectomy within 4 weeks prior to screening
9. Subject received or is planning to receive a haematopoietic stem cell transplantation during the clinical trial
10. Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with all study procedures
11. Known hypersensitivity to any recombinant E. coli-derived product or IMP excipients (Tween, Mannitol)
12. Subjects participating in a concurrent clinical trial or treated with another investigational drug within 4 weeks or 5 terminal half-lives of the drug (whichever is longer) preceding the first dose of IMP
13. History of or current alcohol or drug abuse
14. Any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study
15. Subjects with an active malignancy
16. Subjects with active, serious, life-threatening disease with a life expectancy of less than 6 months
17. Subject was previously treated with SM101 or corresponding placebo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety based on incidence, severity, causality and seriousness of adverse events and laboratory results. Adverse events will be graded using the NCI CTCAE, v 3.0 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim analyses will be performed after the escalation part of the study,
after all extension part patients have completed 3 months follow up and
at the end of the study. |
|
E.5.2 | Secondary end point(s) |
Efficacy
• Proportion of subjects with a platelet count ≥ 50,000/μL at day 22 (-0,5h), 29, 50, 78, 106, 134, 162 and 190.
• Proportion of subjects with a platelet count ≥ 30,000/μL and at least twice the baseline amount (defined at screening study day -7) at day 22 (-0,5h), 29, 50, 78, 106, 134, 162 and 190.
• Mean cumulative duration of a platelet count ≥ 50,000/μL until end of study
• Mean cumulative duration of a platelet count ≥ 30,000/μL and at least twice the baseline amount (defined at screening study day -7) until end of study
• Mean time to reach first platelet count of ≥ 50,000/μL, calculated from baseline at day 1
• Mean time to reach first platelet count of ≥ 30,000/μL and at least twice the baseline amount calculated from baseline at day 1.
• Proportion of subjects requiring rescue medication until end of study
• Total number of days with rescue medication intake until end of study
• Proportion of subjects with dose reduction of concomitant ITP corticosteroid medication
• Mean percentage reduction of concomitant ITP corticosteroid medication at end of study
• Proportion of subjects with WHO bleeding events grade 2 (mild blood loss) or higher until end of study
• Total number of WHO bleeding events grade 2 (mild blood loss) or higher until end of study
• Change of Immunological marker profile and IMP PK parameters
• Proportion of patients with a reduction of autoantibodies against platelet glycoproteins Ib/IX or IIb/IIIa (if any) from baseline (day -7) to day 29, 106 and 190.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See timepoints listed in E.5.2 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Germany |
Poland |
Russian Federation |
Ukraine |
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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
|
The end of the 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.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |