Phase I BP Interferon (IFN) Beta-001

NCT02515695 | Completed Phase 1 DMC

• 2 other identifiers: CE 92/052005DR1151
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

Phase I study aiming at:

• assessing the absolute bioavailability, pharmacokinetic profile, and dose proportionality of interferon beta-1a (HSA-free solution in pre-filled syringes) after i.v. and s.c. administration as well as the pharmacodynamic profile to create the link with available surrogate markers investigated with both formulations used clinically, lyophilisate with HSA (HSA+) and solution without HSA (HSA-);
• gathering further information on safety and tolerability of interferon beta-1a over dose range,including local and systemic tolerance, body temperature, vital signs, and a battery of exploratory sickness behavior tests.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (2)

• 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 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.

  0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 [hours post-dose]

• Composite of interferon beta-1a PD markers

  Serum concentration of three surrogate markers (neopterin and beta2-microglobulin and 2',5' OAS) will be measured

  0, 6, 12, 24, 48, 72, 96, 120, 168 [hours post-dose]

Secondary Outcomes (6)

• 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

  0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose] and then daily if needed until Day 5 or longer until resolution in case of local reaction

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

  Screening and 0, 24 [hours post-dose]

• Composite of vital signs as a measure of safety and tolerability

  Screening and 0, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose]

• Sickness behavior assessment

  0, 2, 4, 6, 8, 10, 12 [hours post-dose]

Study Arms (4)

0.5 MIU i.v. and 1.5 MIU s.c.

EXPERIMENTAL

All 12 subjects participated in 4 periods, receiving 4 different doses of interferon beta-1a from 2 of the 4 possible pairs of treatments. The number of treatment sequences was limited to 6 and the subjects were randomized among the 6 sequences, as one male and one female per sequence. Thus 6 subjects received each dose. The washout period between two injections (Day 1 of subsequent periods) was of 7 days or more.

Drug: Interferon beta-1a

1 MIU i.v. and 3 MIU s.c.

EXPERIMENTAL

All 12 subjects participated in 4 periods, receiving 4 different doses of interferon beta-1a from 2 of the 4 possible pairs of treatments. The number of treatment sequences was limited to 6 and the subjects were randomized among the 6 sequences, as one male and one female per sequence. Thus 6 subjects received each dose. The washout period between two injections (Day 1 of subsequent periods) was of 7 days or more.

Drug: Interferon beta-1a

2 MIU i.v. and 6 MIU s.c.

EXPERIMENTAL

All 12 subjects participated in 4 periods, receiving 4 different doses of interferon beta-1a from 2 of the 4 possible pairs of treatments. The number of treatment sequences was limited to 6 and the subjects were randomized among the 6 sequences, as one male and one female per sequence. Thus 6 subjects received each dose. The washout period between two injections (Day 1 of subsequent periods) was of 7 days or more.

Drug: Interferon beta-1a

4 MIU i.v. and 12 MIU s.c.

EXPERIMENTAL

All 12 subjects participated in 4 periods, receiving 4 different doses of interferon beta-1a from 2 of the 4 possible pairs of treatments. The number of treatment sequences was limited to 6 and the subjects were randomized among the 6 sequences, as one male and one female per sequence. Thus 6 subjects received each dose. The washout period between two injections (Day 1 of subsequent periods) was of 7 days or more.

Drug: Interferon beta-1a

Interventions

Interferon beta-1a DRUG

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

Also known as: Bioferon®

0.5 MIU i.v. and 1.5 MIU s.c.; 1 MIU i.v. and 3 MIU s.c.; 2 MIU i.v. and 6 MIU s.c.; 4 MIU i.v. and 12 MIU s.c.

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: July 24, 2015
• First Posted: August 5, 2015
• Study Start: May 1, 2005
• Primary Completion: July 1, 2005
• Study Completion: July 1, 2005
• Last Updated: August 6, 2015

Record last verified: 2015-08