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BN201 SAD MAD Study in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT03630497
Recruitment Status : Completed
First Posted : August 15, 2018
Last Update Posted : April 10, 2019
Sponsor:
Collaborator:
Simbec Research
Information provided by (Responsible Party):
Bionure Farma SL

Brief 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 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).


Condition or disease Intervention/treatment Phase
Optic Neuritis Optic; Neuritis, With Demyelination Drug: Comparison of BN201 treatment with Placebo Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Actual Study Start Date : May 27, 2018
Actual Primary Completion Date : February 1, 2019
Actual Study Completion Date : February 22, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Period 1 Single Dose SD1 (first dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 1 Single Dose SD2 (second dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 1 Single Dose SD3 (third dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 1 Single Dose SD4 (fourth dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 2 Single Dose SD1 (fifth dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 2 Single Dose SD2 (sixth dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 2 Single Dose SD3 (seventh dose)

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Period 2 Single Dose SD4 (Optional)

(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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Multiple Dose MD1

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201

Experimental: Multiple Dose MD2

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

Drug: Comparison of BN201 treatment with Placebo
Single Dose or Multiple Dose of BN201 IV administration
Other Name: BN201




Primary Outcome Measures :
  1. 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.

  2. Safety: Routine Laboratory Safety Screen on Haematology [ Time Frame: Up to 17 days ]
    Analysis for Haematology

  3. Safety: Routine Laboratory Safety Screen on Urinary Sodium [ Time Frame: Up to 17 days ]
    Analysis for Urinary Sodium

  4. Safety: Routine Laboratory Safety Screen on Biochemistry [ Time Frame: Up to 17 days ]
    Analysis for Biochemistry

  5. Safety: Routine Laboratory Safety Screen on Urinary Potassium [ Time Frame: Up to 17 days ]
    Analysis for Urinary Potassium

  6. Safety: Vital signs Measures on Systolic blood pressure [ Time Frame: Up to 17 days ]
    Check of Systolic blood pressure

  7. Safety: Vital signs Measures on Diastolic blood pressure [ Time Frame: Up to 17 days ]
    Check of Diastolic blood pressure

  8. Safety: Vital signs Measures on oral body temperature [ Time Frame: Up to 17 days ]
    Check of oral body temperature

  9. Safety: Vital signs Measures on Pulse rate [ Time Frame: Up to 17 days ]
    Check of pulse rate

  10. Magnetic resonance imaging (MRI) brain scan [ Time Frame: Up to 17 days ]
    Non-contrast MRI brain scans

  11. 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

  12. Safety: Physical Examination for ear [ Time Frame: Up to 17 days ]
    Examination of ear

  13. Safety: 12-lead Electrocardiography (ECG) Recording [ Time Frame: Up to 17 days ]
    Performance of ECGs in the supine position

  14. Safety: Telemetry Monitoring [ Time Frame: Up to 5 days ]
    Cardiac rhythm measure

  15. Safety: Pain report [ Time Frame: Day 5 ]
    Spontaneous (neuropathic) pain report using Visual Analogue Scale (VAS) tool

  16. Safety: Quantitative Sensory Testing (QST) [ Time Frame: Day 5 ]
    Evaluation of increase in mechano-sensitivity

  17. Safety: Infusion Site Reaction Assessment [ Time Frame: Up to 17 days ]
    Assessment of Infusion Site Reaction

  18. Safety: Holter Monitoring [ Time Frame: Up to 5 days ]
    Cardiac rhythm measure

  19. Safety: Electroencephalography (EEG) Recording [ Time Frame: Up to 5 days ]
    Electrical activity measure

  20. Safety: Concomitant Medication Recording [ Time Frame: Up to 17 days ]
    All prior and concomitant medications taken record

  21. Safety: Physical Examination for nose [ Time Frame: Up to 17 days ]
    Examination of nose

  22. Safety: Physical Examination for throat [ Time Frame: Up to 17 days ]
    Examination of throat

  23. Safety: Physical Examination for eye [ Time Frame: Up to 17 days ]
    Examination of ophthalmological aspects

  24. Safety: Physical Examination for skin [ Time Frame: Up to 17 days ]
    Examination of dermatological aspects

  25. Safety: Physical Examination for cardiovascular [ Time Frame: Up to 17 days ]
    Examination of cardiovascular aspects

  26. Safety: Physical Examination for Respiratory [ Time Frame: Up to 17 days ]
    Examination of respiratory aspects

  27. Safety: Physical Examination for gastrointestinal [ Time Frame: Up to 17 days ]
    Examination of gastrointestinal aspects

  28. Safety: Physical Examination for Central Nervous System [ Time Frame: Up to 17 days ]
    Examination of central nervous system

  29. Safety: Physical Examination for Lymph Nodes [ Time Frame: Up to 17 days ]
    Examination of lymph nodes

  30. Safety: Physical Examination for musculoskeletal [ Time Frame: Up to 17 days ]
    Examination of musculoskeletal aspects


Secondary Outcome Measures :
  1. Pharmacokinetic Parameter: Cmax measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Maximum concentration measurement in plasma

  2. Pharmacokinetic Parameter: Tm concentration measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Time to maximum observed concentration in plasma

  3. Pharmacokinetic Parameter: kel measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Elimination rate constant in plasma

  4. Pharmacokinetic Parameter: t1/2 measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Terminal elimination half-life in plasma

  5. Pharmacokinetic Parameter: AUC 0-τ measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Area under the concentration-time curve (AUC) from 0 to τ, where τ is the dosing interval (0 - 24 h) in plasma

  6. Pharmacokinetic Parameter: AUC 0-t measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Area under the concentration-time curve (AUC) from the time of dosing to the time of the last measurable concentration in plasma

  7. Pharmacokinetic Parameter: AUC 0-inf measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    AUC extrapolated to infinity

  8. Pharmacokinetic Parameter: AUC % measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    extrapolated Residual area

  9. Pharmacokinetic Parameter: Clearance (CL) measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Clearance

  10. Pharmacokinetic Parameter: Vz measurement [ Time Frame: From pre-dose to 24 hours post-start-infusion ]
    Volume of distribution


Other Outcome Measures:
  1. Pharmacodynamic Parameter: Phosphorylation of N-myc downstream regulated 1 (NDRG1) measurement [ Time Frame: Up to 2 hours post start infusion ]
    NDRG1 phosphorylation in PBMCs

  2. Pharmacogenomics Parameter: Sequencing of DNA in blood samples [ Time Frame: Day 1 ]
    Potential genotyping of deoxyribonucleic acid (DNA) sequence variants in blood sample



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

To be confirmed at screening:

  1. Healthy male and female subjects between 18 and 55 years of age.
  2. *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).
  3. *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.
  4. *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.
  5. *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).
  6. *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.
  7. *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.
  8. *Subject with no clinically significant history of previous allergy / sensitivity to BN201 or any of the excipients contained within the IMP.
  9. *Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of IMP.
  10. *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).
  11. Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV) results.
  12. *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.
  13. Subjects with no clinically significant abnormalities in electroencephalogram (EEG) determined within 28 days before first dose of IMP.
  14. *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.
  15. Subject must be available to complete the study (including all follow up visits).
  16. Subject must satisfy the investigator / designee about their fitness to participate in the study.
  17. Subject must be willing and able to sign the written informed consent to participate in the study.
  18. Subjects must not donate sperm for the first dose and for at least 3 months after the last dose of IMP.
  19. 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:

  1. Subject continues to meet all screening inclusion criteria indicated with * (BMI will only apply to screening).
  2. Subject with a negative urinary drugs of abuse screen (including alcohol) prior to dosing.
  3. Female subject with negative pregnancy test.

Exclusion Criteria:

To be confirmed at screening:

  1. 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.
  2. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
  3. A clinically significant history of drug or alcohol abuse.
  4. 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).
  5. Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function).
  6. 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).
  7. 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:

  1. Development of any exclusion criteria since screening.
  2. 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.
  3. Participation in a clinical study since the screening visit.
  4. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03630497


Locations
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United Kingdom
Simbec Research Limited
Merthyr Tydfil, United Kingdom, CF48 4DR
Sponsors and Collaborators
Bionure Farma SL
Simbec Research
Investigators
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Principal Investigator: Annelize Koch, MBChB Simbec Research

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Responsible Party: Bionure Farma SL
ClinicalTrials.gov Identifier: NCT03630497     History of Changes
Other Study ID Numbers: BN201_RDREG_251
2017-001202-14 ( EudraCT Number )
First Posted: August 15, 2018    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bionure Farma SL:
Acute Optic Neuritis (AON)
Demyelination
Optic Neuritis

Additional relevant MeSH terms:
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Neuritis
Optic Neuritis
Demyelinating Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases