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

NCT02480946 | Completed Phase 1 DMC

• 2 other identifiers: 120011A2015-001474-18
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 3

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.

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid Arthritis; Osteoclastogenesis inhibitor; Anti-Inflammatory Agent; Musculoskeletal Diseases; Joint Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

  During the study treatment period

• Part D - Area under the plasma concentration versus time curve (AUC) of MBS2320 and methotrexate

  During the study treatment period

Study Arms (4)

Single Ascending Dose and Food Effect

EXPERIMENTAL

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

Drug: MBS2320; Drug: Placebo

Multiple Ascending Dose

EXPERIMENTAL

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

Drug: MBS2320; Drug: Placebo

Relative Bioavailability

EXPERIMENTAL

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; Drug: Placebo

Drug-Drug Interaction with Methotrexate

EXPERIMENTAL

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; Drug: Methotrexate

Interventions

MBS2320 DRUG

As described in the arm descriptions

Drug-Drug Interaction with Methotrexate; Multiple Ascending Dose; Relative Bioavailability; Single Ascending Dose and Food Effect

Placebo DRUG

As described in the arm descriptions

Multiple Ascending Dose; Relative Bioavailability; Single Ascending Dose and Food Effect

Methotrexate DRUG

Background therapy as described in the arm descriptions

Also known as: Rheumatrex, Trexall, Amethoperin, Mexate

Drug-Drug Interaction with Methotrexate

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Modern Biosciences Ltd: lead
• Covance: collaborator

Study Sites (3)

Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Covance Clinical Research Unit Ltd.

Leeds, West Yorkshire, LS2 9LH, United Kingdom

Location

NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Musculoskeletal Diseases; Joint Diseases

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jim Bush, MBChB,PhD

  Covance

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 25, 2015
• Study Start: July 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 28, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)