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

Primary Purpose

Arthritis, Rheumatoid

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

MBS2320

Placebo

Methotrexate

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Rheumatoid Arthritis, Osteoclastogenesis inhibitor, Anti-Inflammatory Agent, Musculoskeletal Diseases, Joint Diseases

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital
Covance Clinical Research Unit Ltd.
NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Single Ascending Dose and Food Effect

Multiple Ascending Dose

Relative Bioavailability

Drug-Drug Interaction with Methotrexate

Arm Description

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

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

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.

Part D will be a multiple dose study incorporating an open-label, fixed-sequence drug-drug interaction between MBS2320 and methotrexate and biomarker evaluation.

Outcomes

Primary Outcome Measures

Safety and tolerability (incidence of all grade adverse events and dose limiting toxicities during the observation period and/or study treatment periods)

Secondary Outcome Measures

Study Parts A, B and C - Peak Plasma Concentration (Cmax) of MBS2320

Study Parts A, B and C - Area under the plasma concentration versus time curve (AUC) of MBS2320

Study Parts A, B and C Time to peak plasma concentration (Tmax) of MBS2320

Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate

Half-life (T1/2)

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)

Part D - Time to peak plasma concentration (Tmax) of MBS2320 and methotrexate

Part D - Half-life (T1/2) of MBS2320 and methotrexate

Part D - Early response biomarkers of disease activity and bone turnover

CRP and CTX

Full Information

NCT ID

NCT02480946

First Posted

June 16, 2015

Last Updated

March 24, 2017

Sponsor

Modern Biosciences Ltd

Collaborators

Covance

1. Study Identification

Unique Protocol Identification Number

NCT02480946

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

July 2015 (undefined)

Primary Completion Date

March 2017 (Actual)

Study Completion Date

March 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Modern Biosciences Ltd

Collaborators

Covance

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

105 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single Ascending Dose and Food Effect

Arm Type

Experimental

Arm Description

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

Arm Title

Multiple Ascending Dose

Arm Type

Experimental

Arm Description

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

Arm Title

Relative Bioavailability

Arm Type

Experimental

Arm Description

Arm Title

Drug-Drug Interaction with Methotrexate

Arm Type

Experimental

Arm Description

Part D will be a multiple dose study incorporating an open-label, fixed-sequence drug-drug interaction between MBS2320 and methotrexate and biomarker evaluation.

Intervention Type

Drug

Intervention Name(s)

MBS2320

Intervention Description

As described in the arm descriptions

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

As described in the arm descriptions

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

Rheumatrex, Trexall, Amethoperin, Mexate

Intervention Description

Background therapy as described in the arm descriptions

Primary Outcome Measure Information:

Title

Safety and tolerability (incidence of all grade adverse events and dose limiting toxicities during the observation period and/or study treatment periods)

Time Frame

Within 7 days

Secondary Outcome Measure Information:

Title

Study Parts A, B and C - Peak Plasma Concentration (Cmax) of MBS2320

Time Frame

Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose

Title

Study Parts A, B and C - Area under the plasma concentration versus time curve (AUC) of MBS2320

Time Frame

Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose

Title

Study Parts A, B and C Time to peak plasma concentration (Tmax) of MBS2320

Time Frame

Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose

Title

Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate

Description

Half-life (T1/2)

Time Frame

During the study treatment period

Title

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

Description

Peak Plasma Concentration (Cmax), Area under the plasma concentration versus time curve (AUC), Time to peak plasma concentration (Tmax), Half-life (T1/2)

Time Frame

During the study treatment period

Title

Part D - Time to peak plasma concentration (Tmax) of MBS2320 and methotrexate

Time Frame

During the study treatment period

Title

Part D - Half-life (T1/2) of MBS2320 and methotrexate

Time Frame

During the study treatment period

Title

Part D - Early response biomarkers of disease activity and bone turnover

Description

CRP and CTX

Time Frame

Day 1 and 16.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jim Bush, MBChB,PhD

Organizational Affiliation

Covance

Official's Role

Principal Investigator

Facility Information:

Facility Name

Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital

City

Liverpool

State/Province

Merseyside

ZIP/Postal Code

L7 8XP

Country

United Kingdom

Facility Name

Covance Clinical Research Unit Ltd.

City

Leeds

State/Province

West Yorkshire

ZIP/Postal Code

LS2 9LH

Country

United Kingdom

Facility Name

NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)

City

London

ZIP/Postal Code

W12 0HS

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

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

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