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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02480946
First Posted: June 25, 2015
Last Update Posted: March 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Covance
Information provided by (Responsible Party):
Modern Biosciences plc
  Purpose
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.

Condition Intervention Phase
Arthritis, Rheumatoid Drug: MBS2320 Drug: Placebo Drug: Methotrexate Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Modern Biosciences plc:

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) [ Time Frame: Within 7 days ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]
  • 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 ]
  • Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate [ Time Frame: During the study treatment period ]
    Half-life (T1/2)

  • Part D - Area under the plasma concentration versus time curve (AUC) of MBS2320 and methotrexate [ Time Frame: During the study treatment period ]
    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 [ Time Frame: During the study treatment period ]
  • Part D - Half-life (T1/2) of MBS2320 and methotrexate [ Time Frame: During the study treatment period ]
  • Part D - Early response biomarkers of disease activity and bone turnover [ Time Frame: Day 1 and 16. ]
    CRP and CTX


Enrollment: 105
Study Start Date: July 2015
Study Completion Date: March 2017
Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Rheumatrex
  • Trexall
  • Amethoperin
  • Mexate

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).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02480946


Locations
United Kingdom
Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital
Liverpool, Merseyside, United Kingdom, L7 8XP
Covance Clinical Research Unit Ltd.
Leeds, West Yorkshire, United Kingdom, LS2 9LH
NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Modern Biosciences plc
Covance
Investigators
Principal Investigator: Jim Bush, MBChB,PhD Covance
  More Information

Responsible Party: Modern Biosciences plc
ClinicalTrials.gov Identifier: NCT02480946     History of Changes
Other Study ID Numbers: 120011A
2015-001474-18 ( EudraCT Number )
First Submitted: June 16, 2015
First Posted: June 25, 2015
Last Update Posted: March 28, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Modern Biosciences plc:
Rheumatoid Arthritis
Osteoclastogenesis inhibitor
Anti-Inflammatory Agent
Musculoskeletal Diseases
Joint Diseases

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors