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

Arthritis, Rheumatoid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02480946
• Other study ID #: 120011A
• Secondary ID: 2015-001474-18
• Status: Completed
• Phase: Phase 1
• First received: June 16, 2015
• Last updated: March 24, 2017
• Start date: July 2015
• Est. completion date: March 2017

Study information

• Verified date: March 2017
• Source: Modern Biosciences plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• MBS2320
As described in the arm descriptions
• Placebo
As described in the arm descriptions
• Methotrexate
Background therapy as described in the arm descriptions

Locations

Country	Name	City	State
United Kingdom	Covance Clinical Research Unit Ltd.	Leeds	West Yorkshire
United Kingdom	Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital	Liverpool	Merseyside
United Kingdom	NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)	London

Sponsors (2)

Lead Sponsor	Collaborator
Modern Biosciences plc	Covance

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate	Half-life (T1/2)	During the study treatment period
Secondary	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
Secondary	Part D - Time to peak plasma concentration (Tmax) of MBS2320 and methotrexate		During the study treatment period
Secondary	Part D - Half-life (T1/2) of MBS2320 and methotrexate		During the study treatment period
Secondary	Part D - Early response biomarkers of disease activity and bone turnover	CRP and CTX	Day 1 and 16.