Clinical trial NCT02517788: Phase I BP Interferon (IFN) Beta-004
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: BioPartners GmbH
First posted: 2015-08-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Composite of interferon beta-1a PK parameters
timeFrame: 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)
Secondary outcomes:
measure: Serum concentration of neopterin (PD marker)
timeFrame: 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)
measure: Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability
timeFrame: Up to Day 7
measure: Composite of local reactions as a measure of local tolerance
timeFrame: 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
measure: Composite of clinical laboratory tests as a measure of safety and tolerability
timeFrame: Screening and 0, 24 [hours post-doses]
measure: Composite of vital signs as a measure of safety and tolerability
timeFrame: 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)
measure: Sickness behavior assessment
timeFrame: 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)
measure: Electrocardiogram (ECG) as a measure of safety and tolerability
timeFrame: Screening and 0, 3 [hours post-dose]
Other outcomes:
Locations:
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Jérôme Biollaz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perrottet N, Brunner-Ferber F, Grouzmann E, Spertini F, Biollaz J, Buclin T, Widmer N. Biases affecting injected doses of an experimental drug during clinical trials. Trials. 2016 Jul 16;17(1):321. doi: 10.1186/s13063-016-1463-5.