Safety and Tolerability Study of MBS2320 in Healthy Subjects and Subjects With Rheumatoid Arthritis

A Four-Part Phase-1 Study Investigating the Tolerability, Safety and Pharmacokinetics (PK) of MBS2320 in Healthy Subjects and in Subjects With Rheumatoid Arthritis (RA) Also Treated With Methotrexate

Rheumatoid arthritis (RA) affects 1 percent of the population worldwide and up to 40 percent of patients don't respond to current treatments. MBS2320, the drug being tested in this trial, represents a new approach to treating RA, with the potential not only to reduce levels of inflammation but to also directly inhibit bone damage.The aim of this study is to test the safety of MBS2320 in healthy volunteers, to find out how MBS2320 levels change in the blood with dose, and to test the safety and compatibility of giving MBS2320 to patients with RA in combination with an existing treatment, methotrexate.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: MBS2320; Drug: Placebo; Drug: Methotrexate

Detailed Description

The study will be conducted in 4 parts (parts A to D). The principal aim of this study is to obtain safety and tolerability data when MBS2320 is administered orally as single and multiple doses to healthy subjects (parts A to C). The effect of MBS2320 on the pharmacokinetics (PK) of the first-line rheumatoid arthritis (RA) therapy, methotrexate (MTX), and the effect of MTX on the PK of MBS2320, will also be evaluated in a cohort consisting of subjects with RA (Part D).

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS2 9LH
      • Covance Clinical Research Unit Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Principal Inclusion Criteria:

Parts A, B, and C.

• Healthy males or females between 18 and 60 years of age.
• A body mass index (BMI) between 18.0 and 30.0 kg/m2.
• Female subjects will be of non-childbearing potential or postmenopausal as defined by the protocol.
• Female subjects must not be pregnant.

Part D

• Subjects will be otherwise healthy males or females with a diagnosis of RA between 18 and 70 years of age.
• Subjects will have a BMI between 18.0 and 30.0 kg/m2.
• Female subjects must not be pregnant.
• Subjects must have been treated with, and tolerated, oral or subcutaneous MTX for a minimum of 3 months prior to screening entry.

Principal Exclusion Criteria:

Parts A, B, and C.

• Male subjects who do not agree to use appropriate contraception.
• Female subjects who are receiving HRT who do not agree to use appropriate contraception.
• Subjects who have donated blood in the 3 months, plasma in the 7 days or platelets in the 6 weeks prior to screening.
• Subjects who consume more than the permitted alcohol requirement, who have a significant history of alcoholism or drug/chemical abuse.
• Subjects who are unwilling to abstain from alcohol as required.
• A positive urine drug screen, alcohol breath test at screening or first admission.
• Subject has received a live virus vaccination within the 30 days prior to first dose administration.
• Subjects with a positive test for tuberculosis.

Additional Part D Exclusions

• Subjects who have received any medication (except MTX) known to chronically alter drug absorption or elimination processes within 30 days prior to the first dose administration.
• Subjects currently taking any medications other than those allowed per protocol guidelines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose and Food Effect; Part A will be a single-dose, sequential-group, double-blind, placebo-controlled study of MBS2320.	Drug: MBS2320; As described in the arm descriptions; Drug: Placebo; As described in the arm descriptions
Experimental: Multiple Ascending Dose; Part B will be a multiple-dose, sequential-group, double-blind, placebo-controlled study to investigate 3 planned dose levels.	Drug: MBS2320; As described in the arm descriptions; Drug: Placebo; As described in the arm descriptions
Experimental: Relative Bioavailability; Part C will be an open-label, randomised, 2-period crossover relative bioavailability study of MBS2320 in capsules or suspension. The intention is to enrol 8 healthy subjects. Each subject will participate in 2 treatment periods.	Drug: MBS2320; As described in the arm descriptions; Drug: Placebo; As described in the arm descriptions
Experimental: Drug-Drug Interaction with Methotrexate; Part D will be a multiple dose study incorporating an open-label, fixed-sequence drug-drug interaction between MBS2320 and methotrexate and biomarker evaluation.	Drug: MBS2320; As described in the arm descriptions; Drug: Methotrexate; Background therapy as described in the arm descriptions; Other Names: Mexate; Rheumatrex; Trexall; Amethoperin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability (incidence of all grade adverse events and dose limiting toxicities during the observation period and/or study treatment periods)	Within 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Parts A, B and C - Peak Plasma Concentration (Cmax) of MBS2320		Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose
Study Parts A, B and C - Area under the plasma concentration versus time curve (AUC) of MBS2320		Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose
Study Parts A, B and C Time to peak plasma concentration (Tmax) of MBS2320		Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose
Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate	Half-life (T1/2)	During the study treatment period
Part D - Area under the plasma concentration versus time curve (AUC) of MBS2320 and methotrexate	Peak Plasma Concentration (Cmax), Area under the plasma concentration versus time curve (AUC), Time to peak plasma concentration (Tmax), Half-life (T1/2)	During the study treatment period
Part D - Time to peak plasma concentration (Tmax) of MBS2320 and methotrexate		During the study treatment period
Part D - Half-life (T1/2) of MBS2320 and methotrexate		During the study treatment period
Part D - Early response biomarkers of disease activity and bone turnover	CRP and CTX	Day 1 and 16.

Collaborators and Investigators

• Sponsor: Modern Biosciences Ltd
• Collaborators: Covance
• Investigators: Principal Investigator: Jim Bush, MBChB,PhD, Covance

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): March 28, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Joint Diseases; Musculoskeletal Diseases; Anti-Inflammatory Agent; Osteoclastogenesis inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: 120011A; 2015-001474-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No