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

NCT ID: NCT02480946

Last Updated: 2017-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-03-31

Brief Summary

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.

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).

Conditions

Arthritis, Rheumatoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Single Ascending Dose and Food Effect

Part A will be a single-dose, sequential-group, double-blind, placebo-controlled study of MBS2320.

Group Type: EXPERIMENTAL

MBS2320

Intervention Type: DRUG

As described in the arm descriptions

Placebo

Intervention Type: DRUG

As described in the arm descriptions

Multiple Ascending Dose

Part B will be a multiple-dose, sequential-group, double-blind, placebo-controlled study to investigate 3 planned dose levels.

Group Type: EXPERIMENTAL

MBS2320

Intervention Type: DRUG

As described in the arm descriptions

Placebo

Intervention Type: DRUG

As described in the arm descriptions

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.

Group Type: EXPERIMENTAL

MBS2320

Intervention Type: DRUG

As described in the arm descriptions

Placebo

Intervention Type: DRUG

As described in the arm descriptions

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.

Group Type: EXPERIMENTAL

MBS2320

Intervention Type: DRUG

As described in the arm descriptions

Methotrexate

Intervention Type: DRUG

Background therapy as described in the arm descriptions

Interventions

MBS2320

As described in the arm descriptions

Intervention Type: DRUG

Placebo

As described in the arm descriptions

Intervention Type: DRUG

Methotrexate

Background therapy as described in the arm descriptions

Intervention Type: DRUG

Other Intervention Names

Rheumatrex; Trexall; Amethoperin; Mexate

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Covance

INDUSTRY

Sponsor Role: collaborator

Modern Biosciences Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jim Bush, MBChB,PhD

Role: PRINCIPAL_INVESTIGATOR

Covance

Locations

Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital

Liverpool, Merseyside, United Kingdom

Covance Clinical Research Unit Ltd.

Leeds, West Yorkshire, United Kingdom

NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

2015-001474-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

120011A

Identifier Type: -

Identifier Source: org_study_id