Phase I BP Interferon (IFN) Beta-004
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Interventions
- Drug: Interferon beta-1a originalDrug: Interferon beta-1a HSA-free biosimilarDrug: Interferon beta-1a HSA+ biosimilar
- Registration Number
- NCT02517788
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A: Interferon beta-1a in marketed HSA+ solution Interferon beta-1a original 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. Part A: Interferon beta-1a in HSA-free solution Interferon beta-1a HSA-free biosimilar 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. Part A: Interferon beta-1a combined with HSA+ solution Interferon beta-1a HSA+ biosimilar 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. Part B: Interferon beta-1a in marketed HSA+ solution Interferon beta-1a original 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 \[i.e. dose 2 and 4\]). Part B: Interferon beta-1a in HSA-free solution Interferon beta-1a HSA-free biosimilar 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 \[i.e. dose 2 and 4\]).
- Primary Outcome Measures
Name Time Method Composite of interferon beta-1a PK parameters 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
Name Time Method Serum concentration of neopterin (PD marker) 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
Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability Up to Day 7 AE/SAE will be collected from the start of study treatment and until the follow-up visit
Composite of local reactions as a measure of local tolerance 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)
Composite of clinical laboratory tests as a measure of safety and tolerability Screening and 0, 24 [hours post-doses] Clinical laboratory tests will include hematology, clinical chemistry and urinalysis
Composite of vital signs as a measure of safety and tolerability 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
Sickness behavior assessment 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)
Electrocardiogram (ECG) as a measure of safety and tolerability Screening and 0, 3 [hours post-dose] Twelve-lead ECG will be recorded