Phase I BP Interferon (IFN) Beta-004

NCT02517788 | Completed Phase 1 DMC

• 2 other identifiers: CE 93/062006DR1162
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (7)

• 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)

• Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability

  Up to Day 7

• 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

• Composite of clinical laboratory tests as a measure of safety and tolerability

  Screening and 0, 24 [hours post-doses]

• 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)

Study Arms (5)

Part A: Interferon beta-1a in HSA-free solution

EXPERIMENTAL

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

Part A: Interferon beta-1a combined with HSA+ solution

EXPERIMENTAL

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

Part A: Interferon beta-1a in marketed HSA+ solution

ACTIVE COMPARATOR

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

Part B: Interferon beta-1a in HSA-free solution

EXPERIMENTAL

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

Part B: Interferon beta-1a in marketed HSA+ solution

ACTIVE COMPARATOR

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

Interventions

Interferon beta-1a HSA-free biosimilar DRUG

6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution without albumin

Also known as: Bioferon®

Part A: Interferon beta-1a in HSA-free solution; Part B: Interferon beta-1a in HSA-free solution

Interferon beta-1a HSA+ biosimilar DRUG

6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution combined with albumin solution

Also known as: Bioferon®

Part A: Interferon beta-1a combined with HSA+ solution

Interferon beta-1a original DRUG

6 MIU/0.50 mL in pre-filled glass syringe solubilized in HSA and mannitol solution (marketed formulation)

Also known as: Rebif®

Part A: Interferon beta-1a in marketed HSA+ solution; Part B: Interferon beta-1a in marketed HSA+ solution

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• lead ECG without significant abnormalities
• Negative urine drug screen

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead
• BioPartners GmbH: collaborator

Related Publications (1)

• 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.

  PMID: 27423899 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Interferon beta-1a

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Jérôme Biollaz, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: August 5, 2015
• First Posted: August 7, 2015
• Study Start: May 1, 2006
• Primary Completion: July 1, 2006
• Study Completion: July 1, 2006
• Last Updated: August 10, 2015

Record last verified: 2015-08