Clinical Phase I study to assess safety tolerability, pharmacokinetics and pharmacodynamics of ATROSAB (Anti-TNF-receptor 1 monoclonal antibody) in response to single ascending intravenous infusion doses. A single center, randomized, double blind, parallel group and placebo-controlled clinical trial in healthy male subjects
Organizational Data
- DRKS-ID:
- DRKS00004400
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2012-10-04
- Last update in DRKS:
- 2016-06-09
- Registration type:
- Prospective
Acronym/abbreviation of the study
ATR 001
URL of the study
No Entry
Brief summary in lay language
Aim of the current study is to investigate the safety and tolerability of ATROSAB. Furthermore, the results of the study should also give information on the distribution and elimination of ATROSAB from the body. These processes are followed by the drawing of blood samples at defined time points. Also ATROSAB will be tested for anti-inflammatory effects. Therefore, blood samples drawn from the treated volunteers will be stimulated by means of inflammatory substances, outside the body, and the release of specific inflammatory mediators will be investigated.
Brief summary in scientific language
Aim of the study is to investigate the safety, tolerability and pharmacokinetics of intravenously administered ATROSAB. This is a first-in-man study. In addition the results of the study shoul also give first evidence for the potential anti-inflammatory effects of ATROSAB. For that, a special ex-vivo assay is used. Blood samples drawn from the treated volunteers will be stimulated with tumor-necrosis factor (TNF) and the release of cytokines like IL-6 and IL-8 will be measured.
Health condition or problem studied
- Free text:
- Healthy volunteers
- Healthy volunteers:
- Yes
Interventions, Observational Groups
- Arm 1:
- Group A: Healthy volunteers will be included into this double blind, placebo-controlled trial to receive a single intravenous dose of 0.5 mg/kg ATROSAB or placebo. Due to the occurrence of side effects at that dose, dose was reduced in the following groups.
- Arm 2:
- Group B: Healthy volunteers will be included into this double blind, placebo-controlled trial to receive a single intravenous dose of 0.002 mg/kg ATROSAB or placebo.
- Arm 3:
- Group C: Healthy volunteers will be included into this double blind, placebo-controlled trial to receive a single intravenous dose of 0.006 mg/kg ATROSAB or placebo.
- Arm 4:
- Group D: Healthy volunteers will be included into this double blind, placebo-controlled trial to receive a single intravenous dose of 0.018 mg/kg ATROSAB or placebo.
- Arm 5:
- Group E: Healthy volunteers will be included into this double blind, placebo-controlled trial to receive a single intravenous dose of 0.05 mg/kg ATROSAB or placebo.
Endpoints
- Primary outcome:
- Safety and tolerability of ATROSAB: evaluated via clinical laboratory parameters (before, 24, 48 hours, 17, 31, 45 and 59 days after drug administration. Vital parameters (blood pressure, pulse rate, body temperature: before, 5 minutes, 1, 4, 24, 48 hours, 4, 7, 31, 45 and 59 days after drug administration. ECG: before, 5 minutes, 24, 48 hours, 4, 17, 31, 45 and 59 days after drug administration. Documentation of adverse events: before, 5 minutes, 1, 4, 24, 48 hours, 4, 17, 31, 45 and 59 days after drug administration. Local tolerability: before, 5 minutes, 1, 4, 24 and 48 hours after drug administration. Pharmacokinetics of ATROSAB: Blood samples for the determination of pharmacokinetic parameters are drawn at the following time points: before, 5 minutes, 1, 2, 4, 8, 12, 24, 48 hours, 4, 17, 31, 45 and 59 days after drug administration.
- Secondary outcome:
- Pharmacodynamics (anti-inflammatory effects): Anti-inflammatory effects are investigated by means of an ex-vivo assay; therefore blood samples will be stimulated ex vivo with tumor necrosis factor and the release of cytokines will be tested in the assay. These tests will be performed before, 5 minutes, 12, 24, 48 hours, 4, 17, 31, 45 and 59 days after drug administration.
Study Design
- Purpose:
- Treatment
- Allocation:
- Randomized controlled study
- Control:
-
- Placebo
- Phase:
- I
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- Yes
- Assignment:
- Other
- Sequence generation:
- No Entry
- Who is blinded:
-
- Investigator/therapist
- Patient/subject
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- Medical center Focus Clinical Drug Development GmbH Neuss
- Medical center Nuvisan Neu-Ulm
Recruitment period and number of participants
- Planned study start date:
- 2012-12-03
- Actual study start date:
- 2013-02-11
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2014-07-21
- Target Sample Size:
- 35
- Final Sample Size:
- 27
Inclusion Criteria
- Sex:
- Male
- Minimum Age:
- 18 Years
- Maximum Age:
- 45 Years
- Additional Inclusion Criteria:
- Healthy male volunteers who agree to use appropriate contraception methoids; age 18-45 years
Exclusion Criteria
1. Positive test for HIV antibodies, hepatitis B-virus surface antigen (HbsAg), anti-hepatitis-C virus antibodies (Anti-HCV) or no performed test. 2. Subjects with febrile or infectious illness within the last 7 days prior to administration of the IMP. 3. Subjects demonstrating any active physical disease, acute or chronic. 4. History of alcohol or drug abuse. 5. Subjects who have consumed ethanol within 48 hours prior to IMP administration. 6. More than moderate alcohol consumption (> 20 g of ethanol regularly per day or > 245 g regularly per week). 7. Any history or suspicion of barbiturate, amphetamine, benzodiazepine, cocaine, opiates and cannabis abuse. 8. Heavy smoker (> 10 cigarettes per day) and unable to stop smoking during hospitalization 9. History of known hypersensitivity or allergy to monoclonal antibodies or excipients used in the formulation. 10. Demonstrating excess in xanthine consumption (more than 5 cups of coffee or equivalent per day). 11. Consumption of xanthine-containing food or beverages as well as grapefruit juice within 48 hours prior to study drug administration. 12. Strictly vegetarians or vegans. 13. Any cardiovascular diseases or atrioventricular (AV) block (PQ time > 220 ms and/or QTcB > 450 ms at rest). 14. Antibiotic therapy for more than 7 days during the last 3 months. 15. Participation in any other clinical study or donation of more than 400 ml blood during the last 90 days before IMP administration. 16. History of chronic or recurrent metabolic, renal, hepatic, pulmonary, gastrointestinal (e.g., gastric and intestinal ulcer, cholecystectomy), neurological (especially history of epileptic seizures), endocrinological, immunological, psychiatric, or cardio-vascular disease, myopathies and bleeding tendency. 17. Unexplained weight loss or weight gain of more than 5 kg in the month prior to the study. 18. Subjects on a weight reduction program or a medically supervised diet. 19. Use of any medication (self-medication or prescription medication) within one week before IMP administration (or at least 10 times the respective elimination half-life, whichever is longer). 20. Subjects with latent TB (as diagnosed by Quantiferon test). 21. 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 administration of the study drug. 22. Subjects, who have received prior treatment within 1 year with monoclonal antibodies or other biologic agents. 23. Participation in this study on a previous dose level. 24. Subjects who are aware of having had contact to TBC (tuberculosis) patients within the last 3 months.
Addresses
Primary Sponsor
- Address:
- Baliopharm GmbHKarl-Heinz-Beckurts-Strasse 135248 JülichGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- No
Contact for Scientific Queries
- Address:
- Nuvisan GmbHDr. Michael LissyWegenerstraße 1389231 Neu-UlmGermany
- Telephone:
- +49 (0)731 9840 125
- Fax:
- +49 (0)731 9840 355
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.nuvisan.com
Contact for Public Queries
- Address:
- Focus Clinical Drug Development GmbHDr. Grit AndersenStresemannallee 641460 NeussGermany
- Telephone:
- +49 2131 155-0
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Principal Investigator
- Address:
- Nuvisan GmbHDr. Michael LissyWegenerstraße 1389231 Neu-UlmGermany
- Telephone:
- +49 (0)731 9840 125
- Fax:
- +49 (0)731 9840 355
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.nuvisan.com
Sources of Monetary or Material Support
Commercial (pharmaceutical industry, medical engineering industry, etc.)
- Address:
- Baliopharm GmbHKarl-Heinz-Beckurts-Strasse 135248 JülichGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesinstitut für Arzneimittel und MedizinprodukteKurt-Georg-Kiesinger-Allee 353175 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bfarm.de/cln_103/DE/Home/home_node.html
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Ärztekammer NordrheinTersteegenstr. 940474 DüsseldorfGermany
- Telephone:
- +49-211-43021581
- Fax:
- +49-211-43021585
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2012-06-21
- Ethics committee number:
- 2012224
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2012-07-25
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- 2012-002800-42
- Other secondary IDs:
- 1655/01 - pei-nr
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No Entry
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry