Optic NeuritisPhase 1NCT03630497
BN201 SAD MAD Study in Healthy Subjects
A Phase 1 study of Optic Neuritis and Optic; Neuritis, With Demyelination, run by Accure Therapeutics at 1 site in United Kingdom.
Trial summary
The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of BN201 in healthy subjects. This is a phase I, randomised, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Optic Neuritis, Optic; Neuritis, With Demyelination
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 27 May 2018to 22 Feb 2019
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- To be confirmed at screening:
- Healthy male and female subjects between 18 and 55 years of age.
- *Healthy subjects as determined by past medical history and as judged by the PI (including no significant infection in the last 3 months before trial enrolment).
- *Female subject of non-child bearing potential with negative pregnancy test at screening and each admission to the clinical unit. For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy). Menopausal status will be confirmed by demonstrating at screening that levels of follicle stimulating hormone (FSH) fall within the respective pathology reference range. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at Investigator's discretion following consultation with the Sponsor.
- *Female subjects of child bearing potential must be non-pregnant and non-lactating with negative pregnancy test at screening and each admission to the clinical unit.
- *Female subjects of child bearing potential and male subjects with female partners of child bearing potential must take one highly effective contraceptive precaution in addition to one acceptable contraceptive precaution (i.e., barrier precaution) from first dose until 3 months after last dose of IMP (as detailed in Section 9.4.1).
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- *Male subject willing to use an effective method of contraception or 2 effective methods of contraception, i.e., highly effective method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of IMP.
- *Subject with a body weight of ≥ 50.0 kg and ≤100 kg and have a body mass index (BMI) of 18-32 kg/m2. BMI = body weight (kg) / [height (m)]2.
- *Subject with no clinically significant history of previous allergy / sensitivity to BN201 or any of the excipients contained within the IMP.
- *Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of IMP.
- *Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP (N.B. a positive alcohol result may be repeated at Investigator's discretion).
- Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV) results.
- *Subject with no clinically significant abnormalities in 12-lead electrocardiogram ((QTcF ≤ 430 ms) and (PR 120 - 200 ms)) determined within 28 days before first dose of IMP.
- Subjects with no clinically significant abnormalities in electroencephalogram (EEG) determined within 28 days before first dose of IMP.
- *Subject with no clinically significant abnormalities in vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature determined within 28 days before first dose of IMP.
- Subject must be available to complete the study (including all follow up visits).
- Subject must satisfy the investigator / designee about their fitness to participate in the study.
- Subject must be willing and able to sign the written informed consent to participate in the study.
- Subjects must not donate sperm for the first dose and for at least 3 months after the last dose of IMP.
- Subject with no clinically significant abnormalities in brain MRI scan determined within 28 days before first dose of IMP.
- To be re-confirmed on Day -1 / prior to dosing:
- Subject continues to meet all screening inclusion criteria indicated with * (BMI will only apply to screening).
- Subject with a negative urinary drugs of abuse screen (including alcohol) prior to dosing.
- Female subject with negative pregnancy test.
Who cannot join
- To be confirmed at screening:
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of IMP, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
- A clinically significant history of drug or alcohol abuse.
- Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums).
- Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function).
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- Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
- Donation of 450 mL or more blood within the 3 months before the first dose of IMP.
- To be re-confirmed at Day -1 / prior to dosing:
- Development of any exclusion criteria since screening.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements since screening, unless in the opinion of the Investigator and Sponsor's Responsible Physician the medication will not interfere with the study procedures or compromise subject safety.
- Participation in a clinical study since the screening visit.
- Donation of 450 mL or more blood within the 3 months before the first dose of IMP and until at least 3 months after the final study visit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blind, Placebo-controlled, Single (SAD) and Multiple Ascending Dose (MAD) Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BN201 in Healthy Subjects
The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of BN201 in healthy subjects.
This is a phase I, randomised, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of BN201 in healthy subjects following single ascending doses and two cohorts of multiple doses. The study will be conducted in two parts (Part A and Part B). Part A (up to 8 single ascending doses (SD)) will be conducted in 32 subjects (4 interlocking cohorts of 8 subjects). Part B (up to 2 multiple ascending doses (MD)) will be conducted in 16 subjects (2 cohorts of 8 subjects). Subjects in Part A will undergo a screening period (Day -28 to Day -2), two in-patient treatment periods compromising 3 overnight stays (from Day -1 to Day 3) with a wash out period of at least 14 days between dose administrations and a follow up visit 12 to 16 days following administration of IMP. Subjects in Part B will undergo a screening period (Day -28 to Day -2), an in-patient treatment period compromising 7 overnight stays (from Day -1 to Day 7) and a follow up visit 12 to 16 days following final administration of Investigational Medicinal Product (IMP).
Read the detailed description
Screening (Days -28 to -2) Screening assessments will be performed within 28 days of the first dose to ensure the eligibility of participants. Assessments will include medical history, demographics, concomitant medication check, physical examination, body weight, height, BMI, HIV, Hepatitis B and Hepatitis C screen, drugs of abuse and alcohol screen, routine laboratory assessments (biochemistry, haematology and urinalysis), 12-lead ECG, EEG monitoring, brain MRI scan, vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature. Female participants will also be screened for pregnancy and hormone status. A C-SSRS questionnaire will also be performed at screening for Part B only.
Treatment Period
Part A:
Up to four cohorts ((SD1), (SD2), (SD3), (SD4)) of eight subjects will be randomly assigned to receive either two single intravenous doses of BN201, two single intravenous doses of placebo or one single intravenous dose of BN201 and placebo (per treatment period) over two treatment periods (Period 1 and Period 2). Within each cohort, 6 subjects will receive BN201 and 2 subjects will receive placebo. Two "dose leader" subjects will be dosed on the same day, at least 48 h before the remaining subjects in the cohort. Of these two subjects, one will be dosed with BN201 and the other with placebo. The Chief Investigator (or delegate) must confirm it is safe to continue with the dosing of the remainder of the cohort following review of appropriate safety data. The remaining 6 subjects of the cohort (five randomised to active and one to placebo) will then be dosed.
Subjects will be admitted to the clinical unit in the morning of Day -1 and will remain in the unit until the 48 h post dose scheduled assessments and procedures have been performed (Day 3). On Day -1 of each Treatment Period subjects' eligibility will be re-assessed and blood and urine samples will be collected for laboratory safety tests (including drugs of abuse and alcohol screen, biochemistry, haematology, urinalysis and serum pregnancy test). A 12-lead ECG, vital signs (supine systolic and diastolic blood pressure, pulse), body temperature, adverse event and concomitant medication checks will be performed. The intravenous dose of BN201 or placebo will be based on body weight measured on Day -1. An evening snack will be consumed at least 10 hours (h) before (each) dose administration.
After an overnight fast of at least 10 h, dose administration will occur on the morning of Day 1 between 08:00 and 11:00 whilst subjects are in a semi supine position. The subjects will remain in this position until 2 h post-infusion, however other positions are temporarily allowed for scheduled assessment requirements. Fasting will continue until 4 h after start of infusion; a standardised meal will then be administered.
Subjects will be discharged from the clinical unit on Day 3 (48 h post-dose) providing there are no ongoing safety concerns. There will be a wash out period of at least 14 days between dose administrations prior to subjects returning for their treatment 2 scheduled assessments and procedures.
The following assessments will be made during treatment Period 1 and Period 2:
- Safety assessments: Adverse event (AEs) and concomitant medication check, physical examination, laboratory safety assessments (drugs of abuse and alcohol screen, biochemistry, haematology, urinalysis and serum pregnancy test), 12-lead ECG, telemetry, Holter monitoring, EEG monitoring, vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature, infusion site reaction assessment.
- Pharmacokinetics (PK) assessments: Blood sample collection for measurement of BN201 in plasma.
- Pharmacodynamics (PD) assessments: Blood sample collection for measurement of phosphorylation of N-myc downstream-regulated gene 1 (NDGR1) in peripheral blood mononuclear cells (PBMCs).
- Pharmacogenomic assessments: Blood sample will be collected for potential genotyping of deoxyribonucleic acid (DNA) sequence variants to explore potential relationships with PK/PD and or tolerability.
A follow-up visit (including a brain MRI scan) will be conducted 12 to 16 days following each administration of IMP. If all follow-up assessments are satisfactory to the Investigator following Treatment Period 2 the subject will be discharged from the study. If any AEs are ongoing, or any assessments not satisfactory subjects may be recalled to the unit for follow-up assessments until the Investigator is satisfied the subject may be discharged from the study. Subjects will be advised to return or contact the unit at any time if they may be experiencing any adverse effects.
Enrolment of the subsequent cohort will only proceed, if blinded PK and safety data from the previous cohort has been reviewed by the Sponsor and Chief Investigator and is found to be satisfactory.
Part B:
Two cohorts (MD1, MD2) of eight subjects will be randomly assigned to receive either multiple intravenous doses of BN201 or multiple intravenous doses of placebo once daily for five consecutive days (Day 1 to Day 5). Within each cohort, 6 subjects will receive BN201 and 2 subjects will receive placebo. Two "dose leader" subjects will be dosed on the same day, at least 48 h before the remaining subjects in the cohort. Of these two subjects, one will be dosed with BN201 and the other with placebo. The Chief Investigator (or delegate) must confirm it is safe to continue with the dosing of the remainder of the cohort following review of appropriate safety data. The remaining 6 subjects of the cohort (five randomised to active and one to placebo) will then be dosed. The dose levels to be administered will be based on the safety, tolerability and PK results of Part A. Cohort MD1 can only be started if a higher dose level in the SAD part was well tolerated and that simulated PK modelling for multiple dose administration based on PK data from single doses do not suggest that the Cmax threshold of 13.3 μg/mL will be exceeded. Enrolment of MD2 will only proceed if blinded PK and safety data from subjects in MD1 has been reviewed by the Sponsor and Chief Investigator and is found to be satisfactory. A lower dose may be chosen if deemed appropriate following review of PK and safety data from Part A.
Subjects will be admitted to the clinical unit in the morning of Day -1 and will remain in the unit until the scheduled assessments and procedures have been performed on Day 7, 48 h post-last dose. On Day -1 subjects' eligibility will be re-assessed and blood and urine samples will be collected for laboratory safety tests (including drugs of abuse and alcohol screen, biochemistry, haematology, urinalysis and serum pregnancy test). A 12-lead ECG, vital signs (supine systolic and diastolic blood pressure, pulse), body temperature, quantitative sensory testing (QST) and visual analogue scale (VAS) and adverse event and concomitant medication checks will be performed. The intravenous dose of BN201 or placebo will be based on body weight measured on Day -1. An evening snack will be consumed at least 10 h before (each) dose administration.
After an overnight fast of at least 10 h, dose administration will occur on the mornings of Day 1 to Day 5 between 08:00 and 11:00 whilst subjects are in a semi supine position. The subjects will remain in this position until 2 h post-infusion, however other positions are temporarily allowed for scheduled assessment requirements. Fasting will continue until 4 h after start of infusion; a standardised meal will then be administered.
Subjects will be discharged from the clinical unit on Day 7 providing there are no ongoing safety concerns. The following assessments will be made during Day -1 to Day 7:
- Safety assessments: Adverse event (AEs) and concomitant medication check, physical examination, laboratory safety assessments (drugs of abuse and alcohol screen, biochemistry, haematology and urinalysis and serum pregnancy test), 12-lead ECG, telemetry, Holter monitoring, EEG monitoring*, vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature, infusion site reaction assessment, C-SSRS questionnaire, QST and VAS.
- PK assessments: Blood sample collection for measurement of BN201 in plasma.
- PD assessments: Blood sample collection for measurement of phosphorylation of N-myc downstream-regulated gene 1 (NDGR1) in peripheral blood mononuclear cells (PBMCs).
- Pharmacogenomic assessments: Blood sample will be collected for potential genotyping of deoxyribonucleic acid (DNA) sequence variants to explore potential relationships with PK/PD and or tolerability.
- EEG monitoring only performed for Part B Cohort 2 if indicated from results from Part B Cohort 1
A follow-up visit (including a brain MRI scan) will be conducted 12 to 16 days following the subjects' final administration of IMP. If all follow up assessments are satisfactory to the Investigator, the subject will be discharged from the study. If any AEs are ongoing, or any assessments not satisfactory subjects may be recalled to the unit for follow-up assessments until the Investigator is satisfied the subject may be discharged from the study. Subjects will be advised to return or contact the unit at any time if they may be experiencing any adverse effects.
- Being tested
- Comparison of BN201 treatment with Placebo
- Keywords
- Acute Optic Neuritis (AON), Demyelination, Optic Neuritis
- Medical subject headings
- Optic Neuritis, Neuritis, Demyelinating Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comparison of BN201 treatment with PlaceboDrug
Also called BN201
Single Dose or Multiple Dose of BN201 IV administration
| Study group | Role | What they receive |
|---|---|---|
| Period 1 Single Dose SD1 (first dose) | Experimental | Period 1 Group SD1 a single IV infusion of first single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 1 Single Dose SD2 (second dose) | Experimental | Period 1 Group SD2 a single IV infusion of second single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 1 Single Dose SD3 (third dose) | Experimental | Period 1 Group SD3 a single IV infusion of third single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 1 Single Dose SD4 (fourth dose) | Experimental | Period 1 Group SD4 a single IV infusion of fourth single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD1 (fifth dose) | Experimental | Period 2 Group SD1 a single IV infusion of fifth single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD2 (sixth dose) | Experimental | Period 2 Group SD2 a single IV infusion of sixth single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD3 (seventh dose) | Experimental | Period 2 Group SD3 a single IV infusion of seventh single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD4 (Optional) | Experimental | (Optional) Period 2 Group SD4 a single IV infusion of eighth single dose of BN201 (n=6) or placebo (n=2)
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Multiple Dose MD1 | Experimental | MD1 once daily IV infusions of first multiple dose BN201 (n=6) or placebo (n=2) for 5 consecutive days
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
| Multiple Dose MD2 | Experimental | MD2 once daily IV infusions of second multiple dose BN201 (n=6) or placebo (n=2) for 5 consecutive days
Comparison of BN201 treatment with Placebo Receives: Drug: Comparison of BN201 treatment with Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Adverse Events (AEs) and serious adverse events (SAEs) Reporting
All AEs will be recorded, whether considered minor or serious, drug-related or not.
Measured: Up to 17 days
Safety: Routine Laboratory Safety Screen on Haematology
Analysis for Haematology
Measured: Up to 17 days
Safety: Routine Laboratory Safety Screen on Urinary Sodium
Analysis for Urinary Sodium
Measured: Up to 17 days
Safety: Routine Laboratory Safety Screen on Biochemistry
Analysis for Biochemistry
Measured: Up to 17 days
Safety: Routine Laboratory Safety Screen on Urinary Potassium
Analysis for Urinary Potassium
Measured: Up to 17 days
Safety: Vital signs Measures on Systolic blood pressure
Check of Systolic blood pressure
Measured: Up to 17 days
Safety: Vital signs Measures on Diastolic blood pressure
Check of Diastolic blood pressure
Measured: Up to 17 days
Safety: Vital signs Measures on oral body temperature
Check of oral body temperature
Measured: Up to 17 days
Safety: Vital signs Measures on Pulse rate
Check of pulse rate
Measured: Up to 17 days
Magnetic resonance imaging (MRI) brain scan
Non-contrast MRI brain scans
Measured: Up to 17 days
Safety: Suicide Risk assessement
Assessment of Suicide-related thoughts and behaviours using Columbia-Suicide Severity Rating Scale (C-SSRS) Questionnaire
Measured: Up to 17 days
Safety: Physical Examination for ear
Examination of ear
Measured: Up to 17 days
Safety: 12-lead Electrocardiography (ECG) Recording
Performance of ECGs in the supine position
Measured: Up to 17 days
Safety: Telemetry Monitoring
Cardiac rhythm measure
Measured: Up to 5 days
Safety: Pain report
Spontaneous (neuropathic) pain report using Visual Analogue Scale (VAS) tool
Measured: Day 5
Safety: Quantitative Sensory Testing (QST)
Evaluation of increase in mechano-sensitivity
Measured: Day 5
Safety: Infusion Site Reaction Assessment
Assessment of Infusion Site Reaction
Measured: Up to 17 days
Safety: Holter Monitoring
Cardiac rhythm measure
Measured: Up to 5 days
Safety: Electroencephalography (EEG) Recording
Electrical activity measure
Measured: Up to 5 days
Safety: Concomitant Medication Recording
All prior and concomitant medications taken record
Measured: Up to 17 days
Safety: Physical Examination for nose
Examination of nose
Measured: Up to 17 days
Safety: Physical Examination for throat
Examination of throat
Measured: Up to 17 days
Safety: Physical Examination for eye
Examination of ophthalmological aspects
Measured: Up to 17 days
Safety: Physical Examination for skin
Examination of dermatological aspects
Measured: Up to 17 days
Safety: Physical Examination for cardiovascular
Examination of cardiovascular aspects
Measured: Up to 17 days
Safety: Physical Examination for Respiratory
Examination of respiratory aspects
Measured: Up to 17 days
Safety: Physical Examination for gastrointestinal
Examination of gastrointestinal aspects
Measured: Up to 17 days
Safety: Physical Examination for Central Nervous System
Examination of central nervous system
Measured: Up to 17 days
Safety: Physical Examination for Lymph Nodes
Examination of lymph nodes
Measured: Up to 17 days
Safety: Physical Examination for musculoskeletal
Examination of musculoskeletal aspects
Measured: Up to 17 days
Secondary outcomes (10)
Pharmacokinetic Parameter: Cmax measurement
Maximum concentration measurement in plasma
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: Tm concentration measurement
Time to maximum observed concentration in plasma
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: kel measurement
Elimination rate constant in plasma
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: t1/2 measurement
Terminal elimination half-life in plasma
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC 0-τ measurement
Area under the concentration-time curve (AUC) from 0 to τ, where τ is the dosing interval (0 - 24 h) in plasma
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC 0-t measurement
Area under the concentration-time curve (AUC) from the time of dosing to the time of the last measurable concentration in plasma
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC 0-inf measurement
AUC extrapolated to infinity
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC % measurement
extrapolated Residual area
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: Clearance (CL) measurement
Clearance
Measured: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: Vz measurement
Volume of distribution
Measured: From pre-dose to 24 hours post-start-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study start27 May 2018
- Primary completion1 Feb 2019
- Study completion22 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Optic NeuritisStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Accure Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Simbec Research
- Responsible party
- Sponsor
- Investigators
- Annelize Koch, MBChB, Principal investigator, Simbec Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03630497
- Sponsor's protocol ID
- BN201_RDREG_251
- Other IDs
- 2017-001202-14, 2017
- Status last verified
- Apr 2019
- First submitted
- 23 Jul 2018
- Last updated
- 10 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled, Single (SAD) and Multiple Ascending Dose (MAD) Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BN201 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03630497
- Acronym / sponsor ID
- BN201_RDREG_251
- Keywords
- Acute Optic Neuritis (AON), Demyelination, Optic Neuritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Accure TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Simbec Research
- Study start
- 27 May 2018 (actual)
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 22 Feb 2019 (actual)
- First posted
- 15 Aug 2018 (actual)
- 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.
The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of BN201 in healthy subjects.
This is a phase I, randomised, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of BN201 in healthy subjects following single ascending doses and two cohorts of multiple doses. The study will be conducted in two parts (Part A and Part B). Part A (up to 8 single ascending doses (SD)) will be conducted in 32 subjects (4 interlocking cohorts of 8 subjects). Part B (up to 2 multiple ascending doses (MD)) will be conducted in 16 subjects (2 cohorts of 8 subjects). Subjects in Part A will undergo a screening period (Day -28 to Day -2), two in-patient treatment periods compromising 3 overnight stays (from Day -1 to Day 3) with a wash out period of at least 14 days between dose administrations and a follow up visit 12 to 16 days following administration of IMP. Subjects in Part B will undergo a screening period (Day -28 to Day -2), an in-patient treatment period compromising 7 overnight stays (from Day -1 to Day 7) and a follow up visit 12 to 16 days following final administration of Investigational Medicinal Product (IMP).
Detailed description
Screening (Days -28 to -2) Screening assessments will be performed within 28 days of the first dose to ensure the eligibility of participants. Assessments will include medical history, demographics, concomitant medication check, physical examination, body weight, height, BMI, HIV, Hepatitis B and Hepatitis C screen, drugs of abuse and alcohol screen, routine laboratory assessments (biochemistry, haematology and urinalysis), 12-lead ECG, EEG monitoring, brain MRI scan, vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature. Female participants will also be screened for pregnancy and hormone status. A C-SSRS questionnaire will also be performed at screening for Part B only.
Treatment Period
Part A:
Up to four cohorts ((SD1), (SD2), (SD3), (SD4)) of eight subjects will be randomly assigned to receive either two single intravenous doses of BN201, two single intravenous doses of placebo or one single intravenous dose of BN201 and placebo (per treatment period) over two treatment periods (Period 1 and Period 2). Within each cohort, 6 subjects will receive BN201 and 2 subjects will receive placebo. Two "dose leader" subjects will be dosed on the same day, at least 48 h before the remaining subjects in the cohort. Of these two subjects, one will be dosed with BN201 and the other with placebo. The Chief Investigator (or delegate) must confirm it is safe to continue with the dosing of the remainder of the cohort following review of appropriate safety data. The remaining 6 subjects of the cohort (five randomised to active and one to placebo) will then be dosed.
Subjects will be admitted to the clinical unit in the morning of Day -1 and will remain in the unit until the 48 h post dose scheduled assessments and procedures have been performed (Day 3). On Day -1 of each Treatment Period subjects' eligibility will be re-assessed and blood and urine samples will be collected for laboratory safety tests (including drugs of abuse and alcohol screen, biochemistry, haematology, urinalysis and serum pregnancy test). A 12-lead ECG, vital signs (supine systolic and diastolic blood pressure, pulse), body temperature, adverse event and concomitant medication checks will be performed. The intravenous dose of BN201 or placebo will be based on body weight measured on Day -1. An evening snack will be consumed at least 10 hours (h) before (each) dose administration.
After an overnight fast of at least 10 h, dose administration will occur on the morning of Day 1 between 08:00 and 11:00 whilst subjects are in a semi supine position. The subjects will remain in this position until 2 h post-infusion, however other positions are temporarily allowed for scheduled assessment requirements. Fasting will continue until 4 h after start of infusion; a standardised meal will then be administered.
Subjects will be discharged from the clinical unit on Day 3 (48 h post-dose) providing there are no ongoing safety concerns. There will be a wash out period of at least 14 days between dose administrations prior to subjects returning for their treatment 2 scheduled assessments and procedures.
The following assessments will be made during treatment Period 1 and Period 2:
- Safety assessments: Adverse event (AEs) and concomitant medication check, physical examination, laboratory safety assessments (drugs of abuse and alcohol screen, biochemistry, haematology, urinalysis and serum pregnancy test), 12-lead ECG, telemetry, Holter monitoring, EEG monitoring, vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature, infusion site reaction assessment.
- Pharmacokinetics (PK) assessments: Blood sample collection for measurement of BN201 in plasma.
- Pharmacodynamics (PD) assessments: Blood sample collection for measurement of phosphorylation of N-myc downstream-regulated gene 1 (NDGR1) in peripheral blood mononuclear cells (PBMCs).
- Pharmacogenomic assessments: Blood sample will be collected for potential genotyping of deoxyribonucleic acid (DNA) sequence variants to explore potential relationships with PK/PD and or tolerability.
A follow-up visit (including a brain MRI scan) will be conducted 12 to 16 days following each administration of IMP. If all follow-up assessments are satisfactory to the Investigator following Treatment Period 2 the subject will be discharged from the study. If any AEs are ongoing, or any assessments not satisfactory subjects may be recalled to the unit for follow-up assessments until the Investigator is satisfied the subject may be discharged from the study. Subjects will be advised to return or contact the unit at any time if they may be experiencing any adverse effects.
Enrolment of the subsequent cohort will only proceed, if blinded PK and safety data from the previous cohort has been reviewed by the Sponsor and Chief Investigator and is found to be satisfactory.
Part B:
Two cohorts (MD1, MD2) of eight subjects will be randomly assigned to receive either multiple intravenous doses of BN201 or multiple intravenous doses of placebo once daily for five consecutive days (Day 1 to Day 5). Within each cohort, 6 subjects will receive BN201 and 2 subjects will receive placebo. Two "dose leader" subjects will be dosed on the same day, at least 48 h before the remaining subjects in the cohort. Of these two subjects, one will be dosed with BN201 and the other with placebo. The Chief Investigator (or delegate) must confirm it is safe to continue with the dosing of the remainder of the cohort following review of appropriate safety data. The remaining 6 subjects of the cohort (five randomised to active and one to placebo) will then be dosed. The dose levels to be administered will be based on the safety, tolerability and PK results of Part A. Cohort MD1 can only be started if a higher dose level in the SAD part was well tolerated and that simulated PK modelling for multiple dose administration based on PK data from single doses do not suggest that the Cmax threshold of 13.3 μg/mL will be exceeded. Enrolment of MD2 will only proceed if blinded PK and safety data from subjects in MD1 has been reviewed by the Sponsor and Chief Investigator and is found to be satisfactory. A lower dose may be chosen if deemed appropriate following review of PK and safety data from Part A.
Subjects will be admitted to the clinical unit in the morning of Day -1 and will remain in the unit until the scheduled assessments and procedures have been performed on Day 7, 48 h post-last dose. On Day -1 subjects' eligibility will be re-assessed and blood and urine samples will be collected for laboratory safety tests (including drugs of abuse and alcohol screen, biochemistry, haematology, urinalysis and serum pregnancy test). A 12-lead ECG, vital signs (supine systolic and diastolic blood pressure, pulse), body temperature, quantitative sensory testing (QST) and visual analogue scale (VAS) and adverse event and concomitant medication checks will be performed. The intravenous dose of BN201 or placebo will be based on body weight measured on Day -1. An evening snack will be consumed at least 10 h before (each) dose administration.
After an overnight fast of at least 10 h, dose administration will occur on the mornings of Day 1 to Day 5 between 08:00 and 11:00 whilst subjects are in a semi supine position. The subjects will remain in this position until 2 h post-infusion, however other positions are temporarily allowed for scheduled assessment requirements. Fasting will continue until 4 h after start of infusion; a standardised meal will then be administered.
Subjects will be discharged from the clinical unit on Day 7 providing there are no ongoing safety concerns. The following assessments will be made during Day -1 to Day 7:
- Safety assessments: Adverse event (AEs) and concomitant medication check, physical examination, laboratory safety assessments (drugs of abuse and alcohol screen, biochemistry, haematology and urinalysis and serum pregnancy test), 12-lead ECG, telemetry, Holter monitoring, EEG monitoring*, vital signs (supine systolic and diastolic blood pressure, pulse) and body temperature, infusion site reaction assessment, C-SSRS questionnaire, QST and VAS.
- PK assessments: Blood sample collection for measurement of BN201 in plasma.
- PD assessments: Blood sample collection for measurement of phosphorylation of N-myc downstream-regulated gene 1 (NDGR1) in peripheral blood mononuclear cells (PBMCs).
- Pharmacogenomic assessments: Blood sample will be collected for potential genotyping of deoxyribonucleic acid (DNA) sequence variants to explore potential relationships with PK/PD and or tolerability.
- EEG monitoring only performed for Part B Cohort 2 if indicated from results from Part B Cohort 1
A follow-up visit (including a brain MRI scan) will be conducted 12 to 16 days following the subjects' final administration of IMP. If all follow up assessments are satisfactory to the Investigator, the subject will be discharged from the study. If any AEs are ongoing, or any assessments not satisfactory subjects may be recalled to the unit for follow-up assessments until the Investigator is satisfied the subject may be discharged from the study. Subjects will be advised to return or contact the unit at any time if they may be experiencing any adverse effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Period 1 Single Dose SD1 (first dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 1 Group SD1 a single IV infusion of first single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 1 Single Dose SD2 (second dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 1 Group SD2 a single IV infusion of second single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 1 Single Dose SD3 (third dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 1 Group SD3 a single IV infusion of third single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 1 Single Dose SD4 (fourth dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 1 Group SD4 a single IV infusion of fourth single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD1 (fifth dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 2 Group SD1 a single IV infusion of fifth single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD2 (sixth dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 2 Group SD2 a single IV infusion of sixth single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD3 (seventh dose) | Experimental | Drug: Comparison of BN201 treatment with PlaceboPeriod 2 Group SD3 a single IV infusion of seventh single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Period 2 Single Dose SD4 (Optional) | Experimental | Drug: Comparison of BN201 treatment with Placebo(Optional) Period 2 Group SD4 a single IV infusion of eighth single dose of BN201 (n=6) or placebo (n=2) Comparison of BN201 treatment with Placebo |
| Multiple Dose MD1 | Experimental | Drug: Comparison of BN201 treatment with PlaceboMD1 once daily IV infusions of first multiple dose BN201 (n=6) or placebo (n=2) for 5 consecutive days Comparison of BN201 treatment with Placebo |
| Multiple Dose MD2 | Experimental | Drug: Comparison of BN201 treatment with PlaceboMD2 once daily IV infusions of second multiple dose BN201 (n=6) or placebo (n=2) for 5 consecutive days Comparison of BN201 treatment with Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (24 listed)
- Healthy male and female subjects between 18 and 55 years of age.
- *Healthy subjects as determined by past medical history and as judged by the PI (including no significant infection in the last 3 months before trial enrolment).
- *Female subject of non-child bearing potential with negative pregnancy test at screening and each admission to the clinical unit. For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy). Menopausal status will be confirmed by demonstrating at screening that levels of follicle stimulating hormone (FSH) fall within the respective pathology reference range. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at Investigator's discretion following consultation with the Sponsor.
- *Female subjects of child bearing potential must be non-pregnant and non-lactating with negative pregnancy test at screening and each admission to the clinical unit.
- *Female subjects of child bearing potential and male subjects with female partners of child bearing potential must take one highly effective contraceptive precaution in addition to one acceptable contraceptive precaution (i.e., barrier precaution) from first dose until 3 months after last dose of IMP (as detailed in Section 9.4.1).
Key exclusion criteria (13 listed)
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of IMP, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
- A clinically significant history of drug or alcohol abuse.
- Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums).
- Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function).
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 |
|---|---|---|
| Comparison of BN201 treatment with PlaceboAlso: BN201Single Dose or Multiple Dose of BN201 IV administration | Drug | Multiple Dose MD1, Multiple Dose MD2, Period 1 Single Dose SD1 (first dose), Period 1 Single Dose SD2 (second dose), Period 1 Single Dose SD3 (third dose), Period 1 Single Dose SD4 (fourth dose), Period 2 Single Dose SD1 (fifth dose), Period 2 Single Dose SD2 (sixth dose), Period 2 Single Dose SD3 (seventh dose), Period 2 Single Dose SD4 (Optional) |
Primary outcome
Safety: Adverse Events (AEs) and serious adverse events (SAEs) Reporting
Time frame: Up to 17 days
All AEs will be recorded, whether considered minor or serious, drug-related or not.
Safety: Routine Laboratory Safety Screen on Haematology
Time frame: Up to 17 days
Analysis for Haematology
Safety: Routine Laboratory Safety Screen on Urinary Sodium
Time frame: Up to 17 days
Analysis for Urinary Sodium
Safety: Routine Laboratory Safety Screen on Biochemistry
Time frame: Up to 17 days
Analysis for Biochemistry
Safety: Routine Laboratory Safety Screen on Urinary Potassium
Time frame: Up to 17 days
Analysis for Urinary Potassium
Safety: Vital signs Measures on Systolic blood pressure
Time frame: Up to 17 days
Check of Systolic blood pressure
Safety: Vital signs Measures on Diastolic blood pressure
Time frame: Up to 17 days
Check of Diastolic blood pressure
Safety: Vital signs Measures on oral body temperature
Time frame: Up to 17 days
Check of oral body temperature
Safety: Vital signs Measures on Pulse rate
Time frame: Up to 17 days
Check of pulse rate
Magnetic resonance imaging (MRI) brain scan
Time frame: Up to 17 days
Non-contrast MRI brain scans
Safety: Suicide Risk assessement
Time frame: Up to 17 days
Assessment of Suicide-related thoughts and behaviours using Columbia-Suicide Severity Rating Scale (C-SSRS) Questionnaire
Safety: Physical Examination for ear
Time frame: Up to 17 days
Examination of ear
Safety: 12-lead Electrocardiography (ECG) Recording
Time frame: Up to 17 days
Performance of ECGs in the supine position
Safety: Telemetry Monitoring
Time frame: Up to 5 days
Cardiac rhythm measure
Safety: Pain report
Time frame: Day 5
Spontaneous (neuropathic) pain report using Visual Analogue Scale (VAS) tool
Safety: Quantitative Sensory Testing (QST)
Time frame: Day 5
Evaluation of increase in mechano-sensitivity
Safety: Infusion Site Reaction Assessment
Time frame: Up to 17 days
Assessment of Infusion Site Reaction
Safety: Holter Monitoring
Time frame: Up to 5 days
Cardiac rhythm measure
Safety: Electroencephalography (EEG) Recording
Time frame: Up to 5 days
Electrical activity measure
Safety: Concomitant Medication Recording
Time frame: Up to 17 days
All prior and concomitant medications taken record
Safety: Physical Examination for nose
Time frame: Up to 17 days
Examination of nose
Safety: Physical Examination for throat
Time frame: Up to 17 days
Examination of throat
Safety: Physical Examination for eye
Time frame: Up to 17 days
Examination of ophthalmological aspects
Safety: Physical Examination for skin
Time frame: Up to 17 days
Examination of dermatological aspects
Safety: Physical Examination for cardiovascular
Time frame: Up to 17 days
Examination of cardiovascular aspects
Safety: Physical Examination for Respiratory
Time frame: Up to 17 days
Examination of respiratory aspects
Safety: Physical Examination for gastrointestinal
Time frame: Up to 17 days
Examination of gastrointestinal aspects
Safety: Physical Examination for Central Nervous System
Time frame: Up to 17 days
Examination of central nervous system
Safety: Physical Examination for Lymph Nodes
Time frame: Up to 17 days
Examination of lymph nodes
Safety: Physical Examination for musculoskeletal
Time frame: Up to 17 days
Examination of musculoskeletal aspects
10 secondary outcomes
Pharmacokinetic Parameter: Cmax measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: Tm concentration measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: kel measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: t1/2 measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC 0-τ measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC 0-t measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC 0-inf measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: AUC % measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: Clearance (CL) measurement
Time frame: From pre-dose to 24 hours post-start-infusion
Pharmacokinetic Parameter: Vz measurement
Time frame: From pre-dose to 24 hours post-start-infusion
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 10 Apr 2019.
- Individual participant dataSharing planned: No
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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.
Annelize Koch, MBChB principal investigator
Simbec Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Optic Neuritis and Optic; Neuritis, With Demyelination, run by Accure Therapeutics at 1 site in United Kingdom.
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 24 inclusion and 13 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 10 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Safety: Adverse Events (AEs) and serious adverse events (SAEs) Reporting (time frame: Up to 17 days). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Apr 2019.