Multiple Sclerosis, Relapsing-RemittingPhase 1NCT02515695
Phase I BP Interferon (IFN) Beta-001
A Phase 1 study testing Interferon beta-1a in people with Multiple Sclerosis, Relapsing-Remitting, run by Centre Hospitalier Universitaire Vaudois.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Interferon beta-1a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- May 2005to Jul 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 26Show fewer
- 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
About this study
Official title: Bioavailability, Pharmacokinetic and Pharmacodynamic Profile of Interferon Beta-1a (Bioferon®) Administered i.v. and s.c. as Single Doses to Healthy Subjects
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
- Being tested
- Interferon beta-1a
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon beta-1aDrug
Also called Bioferon®
6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Interferon beta-1a |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
AE/SAE will be collected from the start of study treatment and until the follow-up visit
Measured: Up to Day 7
Composite of local reactions as a measure of local tolerance
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).
Measured: 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
Clinical laboratory tests will include hematology, clinical chemistry and urinalysis
Measured: Screening and 0, 24 [hours post-dose]
Composite of vital signs as a measure of safety and tolerability
Vital signs will include body temperature, blood pressure and heart rate
Measured: Screening and 0, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose]
Sickness behavior assessment
Nine parameters will be recorded (Spontaneous movement, Ambient temperature preference, Subjective feelings, Investigator's feelings, Intellectual concentration ability, Hunger/anorexia,Thirst, Paracetamol consumption, Menthol tablet consumption)
Measured: 0, 2, 4, 6, 8, 10, 12 [hours post-dose]
Electrocardiogram (ECG) as a measure of safety and tolerability
Twelve-lead ECG will be recorded
Measured: Screening and 0, 8 [hours post-dose]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2015 (estimated)
- Study startMay 2005
- Primary completionJul 2005
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Collaborators
- BioPartners GmbH
- Responsible party
- Principal investigator, Prof. Jérôme Biollaz, MD, Centre Hospitalier Universitaire Vaudois
- Investigators
- Jérôme Biollaz, MD, Principal investigator, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02515695
- Sponsor's protocol ID
- CE 92/05
- Other IDs
- 2005DR1151
- Status last verified
- Aug 2015
- First submitted
- 24 Jul 2015
- Last updated
- 6 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27423899
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioavailability, Pharmacokinetic and Pharmacodynamic Profile of Interferon Beta-1a (Bioferon®) Administered i.v. and s.c. as Single Doses to Healthy Subjects
- ClinicalTrials.gov ID
- NCT02515695
- Acronym / sponsor ID
- CE 92/05
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Collaborators
- BioPartners GmbH
- Study start
- May 2005
- Primary completion
- Jul 2005 (actual)
- Study completion
- Jul 2005 (actual)
- First posted
- 5 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 0.5 MIU i.v. and 1.5 MIU s.c. | Experimental | Drug: Interferon beta-1aAll 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. |
| 1 MIU i.v. and 3 MIU s.c. | Experimental | Drug: Interferon beta-1aAll 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. |
| 2 MIU i.v. and 6 MIU s.c. | Experimental | Drug: Interferon beta-1aAll 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. |
| 4 MIU i.v. and 12 MIU s.c. | Experimental | Drug: Interferon beta-1aAll 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon beta-1aAlso: Bioferon®6 MIU/0.53 mL in pre-filled glass syringe solubilized in aqueous isotonic buffered solution | Drug | 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. |
Primary outcome
Composite of interferon beta-1a PK parameters
Time frame: 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 [hours post-dose]
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.
Composite of interferon beta-1a PD markers
Time frame: 0, 6, 12, 24, 48, 72, 96, 120, 168 [hours post-dose]
Serum concentration of three surrogate markers (neopterin and beta2-microglobulin and 2',5' OAS) will be measured
6 secondary outcomes
Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability
Time frame: Up to Day 7
Composite of local reactions as a measure of local tolerance
Time frame: 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
Time frame: Screening and 0, 24 [hours post-dose]
Composite of vital signs as a measure of safety and tolerability
Time frame: Screening and 0, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose]
Sickness behavior assessment
Time frame: 0, 2, 4, 6, 8, 10, 12 [hours post-dose]
Electrocardiogram (ECG) as a measure of safety and tolerability
Time frame: Screening and 0, 8 [hours post-dose]
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2015.
- Derived from this study: PubMed 27423899Perrottet 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jérôme Biollaz, MD principal investigator
Centre Hospitalier Universitaire Vaudois
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Interferon beta-1a in people with Multiple Sclerosis, Relapsing-Remitting, run by Centre Hospitalier Universitaire Vaudois.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of interferon beta-1a PK parameters (time frame: 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 [hours post-dose]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02515695, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2015.