|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Asymptomatic antibody-mediated thrombotic thrombocytopenic purpura (TTP) with low ADAMTS13 activity
|Diseases [C] - Blood and lymphatic diseases [C15]
|E.1.2 Medical condition or disease under investigation
|Thrombotic thrombocytopenic purpura
|System Organ Class
|10005329 - Blood and lymphatic system disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess safety and tolerability of single intravenous doses of IdeS in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity
|Secondary objectives of the trial
|To determine the following in patients diagnosed with asymptomatic antibody-mediated TTP with low ADAMTS13 activity
1. ADAMTS13 antigen, activity and antibody (IgG and F(ab’)2) levels following a single intravenous dose of IdeS during 64 days following IdeS dosing
2. Serum concentration of IdeS following a single intravenous dose of IdeS
3. Pharmacodynamic (PD) profile as measured by IgG levels and F(ab’)2 fragments concentrations during 64 days following IdeS dosing
4. Immunogenicity profile of IdeS
|Trial contains a sub-study
|Principal inclusion criteria
|1. Ability to understand and must sign the informed consent form
2. Age 18 years or above
3. Patients diagnosed with acquired TTP with ADAMTS13 levels of ≤ 10 % in clinical remission and with measurable or previously confirmed ADAMTS13 antibodies.
4. Females of childbearing potential and males must use highly effective contraception during the study and at least for 12 weeks after IdeS dosing
Highly effective contraception methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
b. Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
c. Male sterilisation (at least 6 months prior to screening). For female subjects in the study, the vasectomised male partner should be the sole partner for that subject.
d. Combination of any two of the following methods (a+b or a+c or b+c):
d1) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
d2) Placement of an intrauterine device (IUD) or intrauterine system (IUS).
d3) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
|Principal exclusion criteria
|1. Prior malignancy within 5 years excluding adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ
2. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV)
3. Clinical signs of ongoing infectious disease. This includes P-CRP >10.
4. Tested positive for IgE antibodies against IdeS as measured by ImmunoCap.
5. No secondary cause of TTP
6. Rituximab treatment or other antibody-based therapy within 7 days prior to IdeS dosing.
7. Treatment with investigational medicinal product within the last 12 weeks proceeding screening or longer if judged by the investigator to possibly influence the outcome of the current study.
8. Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
9. History of any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at increased risk because of participation in the study, or influence the results or the patient’s ability to participate in the study
10. Hypogammaglobulinemia defined as any values of P-total IgG less than 3 g/L
11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to IdeS (e. g. streptokinase and/or staphylokinase)
12. Substance abuse or other concurrent medical condition that, in the investigator’s opinion, could confound study interpretation or affect the patient’s ability to tolerate or complete the study
13. Investigator considers patient unlikely to comply with study procedures, restrictions and requirements
14. Breast feeding women or women with a positive pregnancy test
15. Previously received IdeS treatment
|E.5 End points
|Primary end point(s)
|Safety as measured by type, frequency and intensity of adverse events and change from baseline in parameters of clinical laboratory tests, vital signs and ECGs.
|Timepoint(s) of evaluation of this end point
|Safety data will be collected and evaluated throughout the study until the last visit on Day 64 after IdeS dosing.
|Secondary end point(s)
|•Change from baseline in ADAMTS13 activity and antibody levels (IgG and F(ab’)2).
•Time for ADAMTS13 activity to return to normal levels
•Number of cases with normalisation of ADAMTS13 at 64 days
•Serum concentration of IdeS
•Change from baseline in pharmacodynamics as measured by level of IgG and F(ab’)2 fragments
•Immunogenicity of IdeS by measuring anti-drug antibodies
|Timepoint(s) of evaluation of this end point
|ADAMTS13 activity and antibody levels (IgG and F(ab’)2) will be collected and evaluated from baseline until end of follow up on Day 64.
Serum concentration of IdeS will be collected and evaluated from baseline until Day 14 following IdeS dosing.
Level of IgG and F(ab’)2 fragments (PD) will be collected and evaluated from baseline until end of follow up on Day 64.
Immunogenicity samples will be collected and evaluated from baseline until end of follow up on Day 64.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|Last subject's last visit
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days