Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase I BP Interferon (IFN) Beta-004

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02517788
Recruitment Status : Completed
First Posted : August 7, 2015
Last Update Posted : August 10, 2015
Sponsor:
Collaborator:
BioPartners GmbH
Information provided by (Responsible Party):
Prof. Jérôme Biollaz, MD, Centre Hospitalier Universitaire Vaudois

Brief Summary:

Phase I study aiming at:

  • establishing the pharmacokinetic profile of interferon beta-1a after i.v. administration of the formulation BioPartners IFN beta-1a without albumin (HSA-free solution in pre-filled syringes) at 18 MIU;
  • investigating the possible impact of albumin on pharmacokinetic profile by comparing 3 different i.v. formulations: BioPartners IFN beta-1a without albumin (HSA-free solution in pre-filled syringes), BioPartners IFN beta-1a with added albumin (HSA+), and Rebif® from Merck-Serono, a registered IFN beta-1a solution containing HSA;
  • establishing the steady state pharmacokinetic profile of BioPartners IFN beta-1a in HSA-free solution after 4 subsequent s.c. doses of 18 MIU given at 48 hour intervals against Rebif® using the same regimen.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Relapsing-Remitting Drug: Interferon beta-1a HSA-free biosimilar Drug: Interferon beta-1a HSA+ biosimilar Drug: Interferon beta-1a original Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparative Pharmacokinetic Profile of Interferon Beta-1a (Bioferon®) Administered as Single i.v. Doses in HSA-free Formulation and HSA+ Solution and as Multiple s.c. Doses in Healthy Subjects
Study Start Date : May 2006
Actual Primary Completion Date : July 2006
Actual Study Completion Date : July 2006

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: Interferon beta-1a in HSA-free solution
Twelve subjects will participate in 3 periods of part A, receiving 18 MIU biosimilar interferon beta-1a without albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.
Drug: Interferon beta-1a HSA-free biosimilar
6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution without albumin
Other Name: Bioferon®

Experimental: Part A: Interferon beta-1a combined with HSA+ solution
Twelve subjects will participate in 3 periods of part A, receiving 18 MIU biosimilar interferon beta-1a with albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.
Drug: Interferon beta-1a HSA+ biosimilar
6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution combined with albumin solution
Other Name: Bioferon®

Active Comparator: Part A: Interferon beta-1a in marketed HSA+ solution
Twelve subjects will participate in 3 periods of part A, receiving 18 MIU original interferon beta-1a with albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.
Drug: Interferon beta-1a original
6 MIU/0.50 mL in pre-filled glass syringe solubilized in HSA and mannitol solution (marketed formulation)
Other Name: Rebif®

Experimental: Part B: Interferon beta-1a in HSA-free solution
Twelve additional volunteers will participate in part B, receiving 4 x 18 MIU biosimilar interferon beta-1a with albumin as s.c. doses at 48 hours intervals as 3 pre-filled syringes (3 sites 1 cm apart in abdominal wall on each dosing day, alternating right side for odd dose [i.e. dose 1 and 3] and left side for even dose [i.e. dose 2 and 4]).
Drug: Interferon beta-1a HSA-free biosimilar
6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution without albumin
Other Name: Bioferon®

Active Comparator: Part B: Interferon beta-1a in marketed HSA+ solution
Part B: Twelve additional volunteers will participate in part B, receiving 4 x 18 MIU original interferon beta-1a with albumin as s.c. doses at 48 hours intervals as 3 pre-filled syringes (3 sites 1 cm apart in abdominal wall on each dosing day, alternating right side for odd dose [i.e. dose 1 and 3] and left side for even dose [i.e. dose 2 and 4]).
Drug: Interferon beta-1a original
6 MIU/0.50 mL in pre-filled glass syringe solubilized in HSA and mannitol solution (marketed formulation)
Other Name: Rebif®




Primary Outcome Measures :
  1. Composite of interferon beta-1a PK parameters [ Time Frame: Part A: 0, 2, 5, 10, 15, 20 [min post-dose] and 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 [hours post-dose] / Part B: 0, 1, 2, 3, 4, 6, 12 [hours post-doses] and 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 [hours post-last dose] (Day 7) ]
    Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) and maximum observed concentration (Cmax) following single dose administration, as well as time to Cmax (tmax; for s.c. injection) will be assessed. Mean residence time (MRT), half-life of elimination (t1/2), clearance (CL), and volume of distribution at steady-state (Vss) will be calculated.


Secondary Outcome Measures :
  1. Serum concentration of neopterin (PD marker) [ Time Frame: Part A: 0, 6, 12, 24, 48, 72, 168 [hours post-doses] / Part B: 0, 6, 12 [hours post-doses] and 0, 6, 12, 24, 48, 72, 96, 120, 144, 168 [hours post-last dose] (Day 7) ]
    Assessment by ELISA after i.v. and after s.c

  2. Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability [ Time Frame: Up to Day 7 ]
    AE/SAE will be collected from the start of study treatment and until the follow-up visit

  3. Composite of local reactions as a measure of local tolerance [ Time Frame: Part A: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose] and longer if needed and until resolution in case of local reaction / Part B: 0, 1, 2, 4, 6, 12 [hours post-dose] on Day 1 and 7, else daily up to Day 9 longer until resolution ]
    Any local symptoms rated as moderate (grade 3 for i.v. and 2 for s.c.) or severe (grade 4 and 5 for i.v.; grade 3 for s.c.) will be reported as an adverse event. The subjective painful sensation following injection of the drug will be assessed using a visual analogue scale (VAS)

  4. Composite of clinical laboratory tests as a measure of safety and tolerability [ Time Frame: Screening and 0, 24 [hours post-doses] ]
    Clinical laboratory tests will include hematology, clinical chemistry and urinalysis

  5. Composite of vital signs as a measure of safety and tolerability [ Time Frame: Part A: Screening and 0, 1, 2, 3, 4, 6, 8, 10, 12, 24 [hours post-dose] / Part B: Screening and 0, 1, 2, 3, 4, 6, 12 [hours post-doses], as well as 0, 1, 2, 3, 4, 6, 8, 12, 24 [hours post-last dose] (Day 7) ]
    Vital signs will include body temperature, blood pressure and heart rate

  6. Sickness behavior assessment [ Time Frame: Part A: 0, 2, 4, 6, 8, 10, 12 [hours post-dose] / Part B: 0, 1, 2, 4, 6, 12 [hours post-dose], as well as 24, 48, 72 [hours post-last dose] (Day 7) ]
    Four parameters will be recorded (general feeling, headache, muscle ache, mood)

  7. Electrocardiogram (ECG) as a measure of safety and tolerability [ Time Frame: Screening and 0, 3 [hours post-dose] ]
    Twelve-lead ECG will be recorded



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and female subjects aged between 18 and 45 years
  • Weight range between 55 and 95 kg for males, 45 and 80 kg for females, providing body mass index (BMI) was between 18 and 29 kg/m2
  • Absence of significant findings in the medical history and physical examination
  • Absence of significant laboratory abnormalities as judged by the investigator.
  • 12-lead ECG without significant abnormalities
  • Negative urine drug screen

Exclusion Criteria:

  • History of major renal, hepatic, immunological, haematological, gastrointestinal, genitourinary, neurological, or rheumatological disorders
  • Active diseases of any type, even if mild, including inflammatory disorders and infections.
  • Pregnant or lactating women or women contemplating becoming pregnant during study. Female subjects of child-bearing potential who did not practice efficient contraception during the study. A pregnancy test in blood was performed at screening and before each period with β-human chorionic gonadotropin for females of child-bearing potential. If pregnancy test was positive, the subject had to be immediately excluded from study and followed until delivery
  • History of severe allergy or of asthma at any time.
  • History of cardiovascular dysfunction
  • Hypertension
  • Sick sinus syndrome or known long QT syndrome
  • Presence of QTc  > 440 msec or pronounced sinus bradycardia (<40 bpm/min), even if elicited by sport
  • Dark skin preventing local tolerance assessment or abnormal cutaneous reaction e.g. urticaria or papular dermographism
  • Intense sport activities.
  • Any clinically significant laboratory value on screening that were not within normal range on single repeat
  • Positive hepatitis B & C antigen screen
  • Positive HIV antibody screen or screen not performed
  • Any recent acute illness or sequelae thereof which could expose the subject to a higher risk or might confound the results of the study
  • Treatment in the previous three months with any drug known to have well-defined potential for toxicity to a major organ
  • History of hypersensitivity to any drug if considered as serious
  • History of alcohol or drug abuse
  • Positive qualitative urine drug test at screening
  • Use of any medication in 2 weeks prior to study and throughout study, including aspirin or other over-the-counter preparation.
  • Blood (500 mL) donation or hemorrhage during the previous three months
  • Participation in a clinical trial in the previous 3 months
  • Smoking
  • Consumption of a large quantity of coffee, tea or equivalent
  • Present consumption of a large quantity of alcohol or wine or equivalent
  • Psychological status which could have had an impact on subject's ability to give informed consent or behavioral tests
  • Any feature of subject's medical history or present condition which, in the investigator's opinion, could confound the results of the study, complicate its interpretation, or represent a potential risk for the subject

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02517788


Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
BioPartners GmbH
Investigators
Layout table for investigator information
Principal Investigator: Jérôme Biollaz, MD Centre Hospitalier Universitaire Vaudois
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Prof. Jérôme Biollaz, MD, Chief Physician, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT02517788    
Other Study ID Numbers: CE 93/06
2006DR1162 ( Registry Identifier: Swissmedic )
First Posted: August 7, 2015    Key Record Dates
Last Update Posted: August 10, 2015
Last Verified: August 2015
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Interferon-beta
Interferon beta-1a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic