An open label, prospective, randomized, multicenter study investigating clinical efficacy and safety of the human normal immunoglobulin for intravenous administration BT595 in patients with chronic primary immune thrombocytopenia (ITP)

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2015-003653-17-DE
• Date of registration: 17/06/2016
• Prospective Registration: Yes
• Primary sponsor: Biotest AG
• Public title: An open label, prospective, randomized, multicenter study investigating clinical efficacy and safety of the human normal immunoglobulin for intravenous administration BT595 in patients with chronic primary immune thrombocytopenia (ITP)
• Scientific title: An open label, prospective, randomized, multicenter study investigating clinical efficacy and safety of the human normal immunoglobulin for intravenous administration BT595 in patients with chronic primary immune thrombocytopenia (ITP)
• Date of first enrolment: 27/01/2017
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003653-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Germany, Hungary, Spain

Contacts

• Name: Clinical Trial Information
• Affiliation: Biotest AG

• Name: Clinical Trial Information
• Affiliation: Biotest AG

Key inclusion & exclusion criteria

Inclusion criteria:
a) Written informed consent obtained from subjects indicating that they understand the purpose of and procedures required for the study and are willing to participate
b) Male or female, aged 18 through 75 years, inclusive
c) Diagnosis of chronic ITP (>12 months’ duration), including diagnosis of refractory ITP, and as defined by the International Working Group (Rodeghiero et al, 2009), where ITP is described as an autoimmune disorder characterized by isolated thrombocytopenia in the absence of other causes or disorders that may be associated with thrombocytopenia
d) Treatment is indicated because of a high risk of bleeding or a need to raise the platelet count
e) Mean screening platelet count of <30×109/L from 3 qualifying platelet counts performed within approximately 7 to 14 days before the start of treatment, with no individual platelet count above 35×109/L. The subject may be rescreened if the mean screening platelet count is =30×109/L.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
a) Pregnancy or unreliable contraceptive measures or lactation period (females only)
b) Known intolerance to immunoglobulins or comparable substances (e.g., vaccination reaction)
c) Known intolerance to proteins of human origin or known allergic reactions to components of the study product
d) Participation in another clinical study within 90 days before entering the study or during the study and/or previous participation in this study
e) Employee or direct relative of an employee of the contract research organization, the study site, or Biotest
f) Secondary thrombocytopenia or acquired medical conditions known to be associated with secondary thrombocytopenia, such as chronic lymphocytic leukemia; lymphoma; multiple myeloma; thyroid disease; or other forms of thrombocytopenia, such as drug induced thrombocytopenia; cirrhotic liver diseases; antiphospholipid syndrome; environmental thrombocytopenia; and bone marrow diseases
g) Severe concomitant diseases that in the judgment of the investigator will interfere with the study, such as autoimmune hemolytic anemia, acute renal failure, and noncontrolled arterial hypertension
h) Laboratory findings (e.g., abnormal laboratory values for hemoglobin, transaminase levels [alanine aminotransferase, aspartate aminotransferase], total bilirubin, creatinine, blood urea nitrogen, and immunoglobulins G, A, M) that preclude participation
i) Positive Coombs test (direct and indirect)
j) Planned invasive procedures during the time frame of the study
k) Maintenance therapy with intravenous immunoglobulins (IVIgs) or infusion of IVIgs within 3 months before start of the study
l) Unresponsive to previous IVIg treatment
m) Additional therapy with high dose corticosteroids (equivalent to >30 mg prednisone/day), thrombopoietin receptor agonists, and/or immunosuppressives and/or other therapies (e.g., infusion of platelets) within 1 month before the start of the study (Note: Subjects on stable doses of ITP active treatment must not have modified the dose in the preceding 2 weeks and must maintain their prestudy dose during the study. Corticosteroids should not be given as a premedication. Rescue therapy with short courses [i.e., 1 to 4 days] of high dose steroids and IVIgs are allowed up to 2 weeks before study inclusion.)
n) History of thrombotic events (including myocardial infarction, cerebral vascular accident [including stroke], pulmonary embolism, and deep vein thrombosis) 6 months before treatment start with BT595 or the presence of significant risk factors for thrombotic events
o) Therapy with live attenuated virus vaccines 3 months before start of the study
p) Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic primary immune thrombocytopenia (ITP)
MedDRA version: 19.0 Level: LLT Classification code 10051057 Term: Idiopathic thrombocytopenia System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: IgG Next Generation
Product Code: BT595
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Human Normal Immunoglobulin (iv)
Current Sponsor code: BT595
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN (IV)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: The main purpose of this study is to assess the efficacy and safety of BT595 in adult subjects with chronic ITP. The primary objective of the study is to determine the rate of subjects with a response. A response is defined as a platelet count of =30×109/L and at least a 2 fold increase of the baseline count, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding.

Secondary Objective: The secondary objective of this study, in addition to further efficacy assessments, is to evaluate the safety of BT595.

Timepoint(s) of evaluation of this end point: Day1, Day2 through Day5, Day8, Day15, Day22, + Day29 approx. Day36

Primary end point(s): Rate of subjects with response (R): defined as subjects with a platelet count of =30×109/L and at least a 2 fold increase of the baseline count, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day1, Day2 through Day5, Day8, Day15, Day22, + Day29 approx. Day36

Secondary end point(s): Number and percentage of subjects with:
- Complete response (CR): defined as a platelet count =100×109/L, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding.
- No response (NR): defined as subjects without R, i.e., defined as a platelet count <30×109/L or less than a 2 fold increase of baseline platelet count, confirmed on at least 2 separate occasions, approximately 1 day apart, or bleeding.
- Loss of response: only in subjects who previously had CR or R, defined as platelet count <100×109/L or bleeding (from CR) or <30×109/L or less than 2 fold increase of baseline platelet count, or bleeding (from R). Platelet counts confirmed on at least 2 separate occasions approximately 1 day apart.
• Time to R: defined as the time from the start of treatment to time of achievement of R or CR.
• Duration of R: defined as the time from the achievement of CR or R to loss of CR or R.
• Number and percentage of subjects with response to =50×109/L: defined as a platelet count increase to at least =50×109/L within 7 days of the first BT595 infusion.
• Subject’s maximum platelet count achieved.
• Time to subject’s maximum platelet count.
• Time course of platelet count.
• Occurrence of bleeding symptoms assessed by physical examination using both the ITP specific bleeding assessment tool (Rodeghiero et al, 2013) and the World Health Organization bleeding scale (Miller et al, 1981).

Secondary ID(s)

992

Source(s) of Monetary Support

Biotest AG

Ethics review

Status: Approved
Approval date:
Contact: