Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SM101-101-hv-08
Study information
Scientific title
A First-in-Human Phase I, double-blind, randomised, placebo-controlled study in healthy male volunteers to investigate the safety, tolerability and pharmacokinetics of recombinant human soluble Fc gamma receptor IIb, sFcγRIIb (SM101) administered intravenously as single ascending doses
Acronym
Study hypothesis
The primary objective of this first-in-human study is to evaluate the safety and tolerability of escalating single doses of intravenously administered sFcγRIIb (SM101).
The secondary objective of this study is to assess the pharmacokinetic profile of sFcγIIRb (SM101) in healthy male subjects.
Ethics approval
Ethics Committee approval was obtained from the Aerztekammer Nordrhein on 08/04/2009 (ref 2008402)
Study design
Single-centre double-blind randomised placebo controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Chronic Adult Idiopathic Thrombocytopenic Purpura
Intervention
sFcγRIIb (SM101) is a recombinant, soluble, non-glycosylated version of the human Fcγ receptor FcγRIIb.
Seven consecutive regular dose groups (0.004, 0.04, 0.4, 1, 2.5, 5 and 10 mg/ kg) will receive one single intravenous administration of sFcγRIIb (SM101) or placebo over 60 minutes under fasted conditions. Further 4 intermediate dose groups may be included, if deemed necessary for safety reasons. Each dose group consists of 6 subjects (4 verum, 2 placebo). Decision on dose escalation will be subject to an independent DSMB.
After a 14-day screening period the subjects will either be enrolled in the verum or placebo arm and will be hospitalised one day before treatment start (day -1). They will be discharged 72 hours after dosing (day 4) and return to the site on day 6, 8 and 12 for ambulatory visits. The active part of the study will be completed on day 15 (conclusion visit). Subjects will attend a follow-up visit 6 months and 1 year after dosing to collect further safety data.
Intervention type
Drug
Phase
Phase I
Drug names
Recombinant human soluble Fc gamma receptor IIb, sFcγRIIb (SM101)
Primary outcome measure
Safety assessments:
1. Haematology, clinical chemistry, coagulation parameters, urinalysis (screening, day -1, pre-dose and 6, 24, 48 and 72 hours after drug administration and on days 6, 8, 12, and 15, follow-up (FU) at 6 months and FU 1 year)
2. IL-6 and CRP (pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 hours after start of infusion and on days 6, 8, 12 and day 15, FU 6 months and FU 1 year)
3. Vital signs, 12-lead ECG (screening, day -1, and 8, 10, 12, 16, 24, 36, 48 and 72 hours after drug administration and on day 15, FU 6 months and FU 1 year)
4. Physical examination (screening, day -1, 24 and 48 hours after drug administration and on day 4 before discharge, day 15, FU 6 months and FU 1 year)
5. Local tolerability (day 1 at 0.25, 0.5, 1, 2, 4 and 12 hours after start of infusion, days 2 and 3 and before discharge on day 4)
6. Adverse events (The National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v 3.0)
Secondary outcome measures
Pharmacokinetic analysis:
Pre-dose, 0.25, 0.5, 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after start of infusion
Overall trial start date
30/04/2009
Overall trial end date
02/10/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male, Caucasian subjects aged between 18-40 years (inclusive)
2. Healthy subjects as determined by medical history, physical examination including vital signs, electrocardiography (ECG) and clinical laboratory testing
3. Body weight between 70-90 kg and body mass index (BMI) between 19 and 28 kg/m^2, extremes included
4. ECG recording based on a 12-lead ECG which is normal (PR <210 ms, QRS <110 ms, QTC 380-430 ms) or contains only slight deviations deemed to be of no clinical relevance by the investigator
5. Normal vital signs (after 5 minutes resting), blood pressure values (systolic >=100 and <=140 mmHg, diastolic >=50 and <=90 mmHg), heart rate between 40 and 90 beats per minute (bpm), body temperature <37.5°C
6. Subjects who are able and willing to give written informed consent
7. Normal white blood cell count, C-reactive protein (CRP) and interleukin-6 (IL-6) at screening and on the day before treatment start
8. Subjects must be using two acceptable methods for contraception (e.g. spermicide and condom) during the study and refrain from fathering a child in the 3 months following dosing
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
42
Participant exclusion criteria
1. In the opinion of the investigator subjects with clinically significant history or presence of cardiovascular, respiratory, renal, hepatic, metabolic, endocrinological, gastrointestinal, hematological, neurological, dermatological, psychiatric diseases, cancer or other major diseases
2. Infection or known inflammatory process
3. Subjects with known autoimmune diseases or immunodeficiency or known family history of autoimmune diseases or immunodeficiency
4. Clinical significant allergic disease
5. Subjects with known serum hepatitis or who are carriers of the hepatitis B surface antigen or hepatitis C antibodies or with a positive result to the test for HIV 1/2 antibodies
6. Subjects who have received an investigational drug and/or a vaccination within 3 months prior to start of the treatment in study and those who anticipate receipt of a vaccine within 2 months after the last dose of study drug
7. Subjects, who have received prior treatment within 1 year with monoclonal antibodies or other biologic agents
8. The use of any concomitant prescription or non-prescription medication within 14 days prior to the first administration of study medication until follow-up; or treatment with medication that may affect immune function (e.g. immunoglobulins, corticosteroids) within 6 months before dosing
9. Donation of blood (>400 ml) or blood products within the last 3 months prior to admission to the clinical unit or plasmapheresis within 4 weeks prior to study start
10. Definite or suspected personal history of adverse reactions or hypersensitivity to drugs especially to the trial compounds (E. coli-derived proteins, Tween, mannitol) or to compounds with a similar structure
11. Subjects who drink more than 5 cups or glasses of coffee, tea and/or cola per day
12. Subjects with a presence or history of drug and/or alcohol abuse or an average daily intake of more than 20 g alcohol per day
13. Subjects with a positive test for alcohol or drugs at screening and on the day before treatment start
14. Smokers of >5 cigarettes/day or equivalent
15. Subjects who are unlikely to be compliant and attend scheduled clinic visits as required
16. Participation in this study on a previous dose level
Recruitment start date
30/04/2009
Recruitment end date
02/10/2009
Locations
Countries of recruitment
Germany
Trial participating centre
FOCUS Clinical Drug Development GmbH
Neuss
41460
Germany
Sponsor information
Organisation
SuppreMol GmbH (Germany)
Sponsor details
Am Klopferspitz 19
Martinsried
82152
Germany
Sponsor type
Industry
Website
Funders
Funder type
Government
Funder name
German Federal Ministry of Education and Research (Bundesministerium Fur Bildung und Forschung [BMBF]) (Germany) , Grant number: 01GU0623
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list