Phase I BP Interferon (IFN) Beta-004

NCT ID: NCT02517788

Last Updated: 2015-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2006-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Interferon beta-1a HSA-free biosimilar

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Interferon beta-1a HSA+ biosimilar

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Interferon beta-1a original

Intervention Type: DRUG

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

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 \[i.e. dose 2 and 4\]).

Group Type: EXPERIMENTAL

Interferon beta-1a HSA-free biosimilar

Intervention Type: DRUG

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

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 \[i.e. dose 2 and 4\]).

Group Type: ACTIVE_COMPARATOR

Interferon beta-1a original

Intervention Type: DRUG

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

Interventions

Interferon beta-1a HSA-free biosimilar

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

Intervention Type: 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

Intervention Type: DRUG

Interferon beta-1a original

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

Intervention Type: DRUG

Other Intervention Names

Bioferon®; Bioferon®; Rebif®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

BioPartners GmbH

INDUSTRY

Sponsor Role: collaborator

Centre Hospitalier Universitaire Vaudois

OTHER

Sponsor Role: lead

Responsible Party

Prof. Jérôme Biollaz, MD

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jérôme Biollaz, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudois

References

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.

Reference Type: DERIVED

PMID: 27423899 (View on PubMed)

Other Identifiers

2006DR1162

Identifier Type: REGISTRY

Identifier Source: secondary_id

CE 93/06

Identifier Type: -

Identifier Source: org_study_id