Clinical trial NCT02480946: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Arthritis, Rheumatoid
Keywords: Rheumatoid Arthritis
Osteoclastogenesis inhibitor
Anti-Inflammatory Agent
Musculoskeletal Diseases
Joint Diseases
Lead sponsor: Modern Biosciences Ltd
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2015-06-25
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Safety and tolerability (incidence of all grade adverse events and dose limiting toxicities during the observation period and/or study treatment periods)
timeFrame: Within 7 days
Secondary outcomes:
measure: Study Parts A, B and C - Peak Plasma Concentration (Cmax) of MBS2320
timeFrame: Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose
measure: Study Parts A, B and C - Area under the plasma concentration versus time curve (AUC) of MBS2320
timeFrame: Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose
measure: Study Parts A, B and C Time to peak plasma concentration (Tmax) of MBS2320
timeFrame: Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose
measure: Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate
timeFrame: During the study treatment period
measure: Part D - Area under the plasma concentration versus time curve (AUC) of MBS2320 and methotrexate
timeFrame: During the study treatment period
measure: Part D - Time to peak plasma concentration (Tmax) of MBS2320 and methotrexate
timeFrame: During the study treatment period
measure: Part D - Half-life (T1/2) of MBS2320 and methotrexate
timeFrame: During the study treatment period
measure: Part D - Early response biomarkers of disease activity and bone turnover
timeFrame: Day 1 and 16.
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Covance Royal Liverpool Clinical Research Unit,Royal Liverpool University Hospital
state: Merseyside
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit Ltd.
state: West Yorkshire
city: London
country: United Kingdom
facility: NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF)
Study officials:
affiliation: Covance
name: Jim Bush, MBChB,PhD
role: PRINCIPAL_INVESTIGATOR
References: