A phase Ib/IIa clinical trial to investigate the safety and efficacy of recombinant human soluble Fc-gamma receptor IIb (SM101) for intravenous application in the treatment of patients with chronic adult idiopathic thrombocytopenic purpura (ITP)

ISRCTN	ISRCTN47912914
DOI	https://doi.org/10.1186/ISRCTN47912914
Secondary identifying numbers	SM101-201-itp-09

Submission date: 04/02/2010
Registration date: 18/05/2010
Last edited: 19/04/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Sascha Tillmanns
Scientific

Am Klopferspitz 19
Martinsried/ Munich
82152
Germany

Study information

Study design	Randomised multicentre double blind placebo-controlled dose escalation and extension trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A randomised, multicentre, double-blind, placebo-controlled, single/multiple dose escalation phase Ib/IIa clinical trial to investigate the safety and efficacy of recombinant human soluble Fc-gamma receptor IIb (SM101) for intravenous application in the treatment of patients with chronic adult idiopathic thrombocytopenic purpura (ITP)
Study objectives	The primary objective of this trial is to evaluate the safety and tolerability of intravenously administered SM101 at various dose levels in a single/multiple dosing manner in subjects with chronic idiopathic thrombocytopenic purpura (ITP). The secondary objective of this trial is to evaluate the efficacy, e.g. platelet count, pharmacokinetic and immunological parameters of intravenous (iv) administered SM101. As of 19/04/2011 the anticipated end date for this trial has been extended from 31/01/2011 to 26/10/2012.
Ethics approval(s)	1. Russia: Ethics Committee of the Federal Service on Surveillance in Health Care and Social Development approved on the 21st October 2009 2. Belgium: K.U. LEUVEN Hospitals Medical Ethics Committee approved on the 6th January 2010 3. Poland: Komisja Bioetyczna Slaskiego Uniwersytetu Medycznego w Katowicach approved on the 5th January 2010 4. Germany: Ethik-Kommission des Fachbereichs Medizin der Justus-Liebig Universitaet Giessen approved on the 14th January 2010 5. Ukraine: Ministry of Health of Ukraine, Central Ethics Committee approved on the 1st June 2010
Health condition(s) or problem(s) studied	Chronic adult idiopathic thrombocytopenic purpura
Intervention	SM101 is a recombinant, soluble, non-glycosylated version of the human Fc- receptor Fc-RIIb. This trial consists of a dose escalation and an extension part. In the dose escalation part, each dose group consists of 4 verum and 2 placebo patients who will receive verum or placebo as a single administration. The patients will be followed up for 4 weeks and will then continue with 4 weekly injections of verum or placebo. With an additional follow-up period of 12 weeks, the patients of one dose group complete their study participation. Extension part: The extension part will be conducted with an additional 15 newly recruited patients (10 verum, 5 placebo) in a parallel fashion and the subjects will receive a total of 4 IMP administrations. The subjects will then be followed for 3 months.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Recombinant human soluble Fc-gamma receptor IIb (SM101)
Primary outcome measure	Incidence, severity, causality and seriousness of adverse events (AEs), laboratory results and AEs of special interest including bleeding events. AEs will be graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse Events will be recorded at an ongoing basis at every visit performed throughout the study (dose escalation part: screening, week 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20; extension part: screening, week 1, 2, 3, 4, 5, 8, 12, 16).
Secondary outcome measures	1. Proportion of subjects with a substantial platelet response defined as: 1.1. Platelet count greater than or equal to 30,000/µL from at least two blood samples, and 1.2. At least two-fold increase of platelet count from baseline values from at least two blood samples 2. The following will be defined as efficacy end-points: 2.1. Mean time to reach substantial platelet response 2.2. Mean duration of platelet count greater than or equal to 30,000/µL 2.3. Mean time to reach first platelet count of greater than or equal to 30,000/µL 2.4. Proportion of subjects requiring rescue medication until end of study 2.5. Proportion of subjects with World Health Organisation (WHO) bleeding events grade 2 (mild blood loss) or higher until end of study 2.6. Immunological markers and IMP PK parameters The platelet count will be determined at every visit performed throughout the study (dose escalation part: screening, week 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20; extension part: screening, week 1, 2, 3, 4, 5, 8, 12, 16). On treatment days (escalation part: days 1, 36, 43, 50 and 47; extension part: days 1, 8, 15 and 22) the platelet count will be measured 0.5 hours prior to dosing and 2, 4, 12, 24 and 48 hours after start of IMP administration.
Overall study start date	07/04/2010
Completion date	26/10/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	36 + 15
Key inclusion criteria	1. Written informed consent prior to any study related procedure 2. Male or female subjects aged 18 to 75 years, with or without splenectomy 3. Diagnosis of chronic idiopathic thrombocytopenic purpura (ITP) based on subject's history, physical examination, blood count and blood film examination according to the British Society for Haematology (BSH) and American Society of Hematology (ASH) guidelines for at least 6 months 4. Subject has previously received at least one ITP therapy 5. Platelet count less than 30,000/µL from at least two measurements 6. Subjects greater than 60 years of age must have had a documented history of chronic ITP with a bone marrow report to confirm the diagnosis
Key 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 3. Subject received rituximab or any other B-cell depleting agent within 24 months preceding the first dose of investigational medical product (IMP) 4. All other previously completed ITP treatment must achieve at least 5 times their terminal half-life prior to first administration of IMP 5. Subject receives concomitant ITP medication other than corticosteroids, except rescue medication during the clinical trial 6. Splenectomy within 4 weeks prior to screening 7. History of or current alcohol or drug abuse 8. Any condition which in the judgment of the Investigator would place the subject at undue risk or interfere with the results of the study
Date of first enrolment	07/04/2010
Date of final enrolment	26/10/2012

Locations

Countries of recruitment

Belgium
Germany
Poland
Russian Federation
Ukraine

Study participating centre

Am Klopferspitz 19

Martinsried/ Munich
82152
Germany

Sponsor information

SuppreMol GmbH (Germany)
Industry

Am Klopferspitz 19
Martinsried/ Munich
82152
Germany

Website	http://www.suppremol.com
"ROR"	https://ror.org/05jgtkc28

Funders

Funder type

Industry

SuppreMol GmbH (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan