Phase I BP Interferon (IFN) Beta-004

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02517788
• Other study ID #: CE 93/06
• Secondary ID: 2006DR1162
• Status: Completed
• Phase: Phase 1
• First received: August 5, 2015
• Last updated: August 7, 2015
• Start date: May 2006
• Est. completion date: July 2006

Study information

• Verified date: August 2015
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 ß-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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting

Intervention

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
• 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
• Interferon beta-1a original
6 MIU/0.50 mL in pre-filled glass syringe solubilized in HSA and mannitol solution (marketed formulation)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois	BioPartners GmbH

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of interferon beta-1a PK parameters	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.	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)	No
Secondary	Serum concentration of neopterin (PD marker)	Assessment by ELISA after i.v. and after s.c	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)	No
Secondary	Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability	AE/SAE will be collected from the start of study treatment and until the follow-up visit	Up to Day 7	Yes
Secondary	Composite of local reactions as a measure of local tolerance	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)	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	Yes
Secondary	Composite of clinical laboratory tests as a measure of safety and tolerability	Clinical laboratory tests will include hematology, clinical chemistry and urinalysis	Screening and 0, 24 [hours post-doses]	Yes
Secondary	Composite of vital signs as a measure of safety and tolerability	Vital signs will include body temperature, blood pressure and heart rate	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)	Yes
Secondary	Sickness behavior assessment	Four parameters will be recorded (general feeling, headache, muscle ache, mood)	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)	Yes
Secondary	Electrocardiogram (ECG) as a measure of safety and tolerability	Twelve-lead ECG will be recorded	Screening and 0, 3 [hours post-dose]	Yes