BN201 SAD MAD Study in Healthy Subjects

NCT03630497 | Completed Phase 1

• 2 other identifiers: BN201_RDREG_2512017-001202-14
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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).

Conditions

Optic Neuritis; Optic; Neuritis, With Demyelination

Keywords

Acute Optic Neuritis (AON); Demyelination; Optic Neuritis

Outcome Measures

Primary Outcomes (30)

• Safety: Adverse Events (AEs) and serious adverse events (SAEs) Reporting

  All AEs will be recorded, whether considered minor or serious, drug-related or not.

  Up to 17 days

• Safety: Routine Laboratory Safety Screen on Haematology

  Analysis for Haematology

  Up to 17 days

• Safety: Routine Laboratory Safety Screen on Urinary Sodium

  Analysis for Urinary Sodium

  Up to 17 days

• Safety: Routine Laboratory Safety Screen on Biochemistry

  Analysis for Biochemistry

  Up to 17 days

• Safety: Routine Laboratory Safety Screen on Urinary Potassium

  Analysis for Urinary Potassium

  Up to 17 days

• Safety: Vital signs Measures on Systolic blood pressure

  Check of Systolic blood pressure

  Up to 17 days

• Safety: Vital signs Measures on Diastolic blood pressure

  Check of Diastolic blood pressure

  Up to 17 days

• Safety: Vital signs Measures on oral body temperature

  Check of oral body temperature

  Up to 17 days

• Safety: Vital signs Measures on Pulse rate

  Check of pulse rate

  Up to 17 days

• Magnetic resonance imaging (MRI) brain scan

  Non-contrast MRI brain scans

  Up to 17 days

• Safety: Suicide Risk assessement

  Assessment of Suicide-related thoughts and behaviours using Columbia-Suicide Severity Rating Scale (C-SSRS) Questionnaire

  Up to 17 days

• Safety: Physical Examination for ear

  Examination of ear

  Up to 17 days

• Safety: 12-lead Electrocardiography (ECG) Recording

  Performance of ECGs in the supine position

  Up to 17 days

• Safety: Telemetry Monitoring

  Cardiac rhythm measure

  Up to 5 days

• Safety: Pain report

  Spontaneous (neuropathic) pain report using Visual Analogue Scale (VAS) tool

  Day 5

• Safety: Quantitative Sensory Testing (QST)

  Evaluation of increase in mechano-sensitivity

  Day 5

• Safety: Infusion Site Reaction Assessment

  Assessment of Infusion Site Reaction

  Up to 17 days

• Safety: Holter Monitoring

  Cardiac rhythm measure

  Up to 5 days

• Safety: Electroencephalography (EEG) Recording

  Electrical activity measure

  Up to 5 days

• Safety: Concomitant Medication Recording

  All prior and concomitant medications taken record

  Up to 17 days

• Safety: Physical Examination for nose

  Examination of nose

  Up to 17 days

• Safety: Physical Examination for throat

  Examination of throat

  Up to 17 days

• Safety: Physical Examination for eye

  Examination of ophthalmological aspects

  Up to 17 days

• Safety: Physical Examination for skin

  Examination of dermatological aspects

  Up to 17 days

• Safety: Physical Examination for cardiovascular

  Examination of cardiovascular aspects

  Up to 17 days

• Safety: Physical Examination for Respiratory

  Examination of respiratory aspects

  Up to 17 days

• Safety: Physical Examination for gastrointestinal

  Examination of gastrointestinal aspects

  Up to 17 days

• Safety: Physical Examination for Central Nervous System

  Examination of central nervous system

  Up to 17 days

• Safety: Physical Examination for Lymph Nodes

  Examination of lymph nodes

  Up to 17 days

• Safety: Physical Examination for musculoskeletal

  Examination of musculoskeletal aspects

  Up to 17 days

Secondary Outcomes (10)

• Pharmacokinetic Parameter: Cmax measurement

  From pre-dose to 24 hours post-start-infusion

• Pharmacokinetic Parameter: Tm concentration measurement

  From pre-dose to 24 hours post-start-infusion

• Pharmacokinetic Parameter: kel measurement

  From pre-dose to 24 hours post-start-infusion

• Pharmacokinetic Parameter: t1/2 measurement

  From pre-dose to 24 hours post-start-infusion

• Pharmacokinetic Parameter: AUC 0-τ measurement

  From pre-dose to 24 hours post-start-infusion

Other Outcomes (2)

• Pharmacodynamic Parameter: Phosphorylation of N-myc downstream regulated 1 (NDRG1) measurement

  Up to 2 hours post start infusion

• Pharmacogenomics Parameter: Sequencing of DNA in blood samples

  Day 1

Study Arms (10)

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

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

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

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

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

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

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

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

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

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

Drug: Comparison of BN201 treatment with Placebo

Interventions

Comparison of BN201 treatment with Placebo DRUG

Single Dose or Multiple Dose of BN201 IV administration

Also known as: BN201

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)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• \*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.

You may not qualify if:

• 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).
• 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:
• 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.

Sponsors & Collaborators

• Accure Therapeutics: lead
• Simbec Research: collaborator

Study Sites (1)

Simbec Research Limited

Merthyr Tydfil, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Optic Neuritis; Neuritis; Demyelinating Diseases

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Annelize Koch, MBChB

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 15, 2018
• Study Start: May 27, 2018
• Primary Completion: February 1, 2019
• Study Completion: February 22, 2019
• Last Updated: April 10, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)