Phase 2b Study of MBS2320 in Participants With Methotrexate-Refractory RA

A Randomised, Double-Blind, Placebo-Controlled, Dose-Ranging Phase 2b Study to Investigate the Efficacy & Safety of MBS2320 in Participants With Moderate to Severe Active Rheumatoid Arthritis With Inadequate Response to Methotrexate Alone

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 prevent bone damage. The aim of this project is to test the safety, tolerability and efficacy of MBS2320 in patients with RA in combination with an existing treatment, methotrexate.

Approximately 224 participants with moderate to severe active RA who have not responded to treatment with Methotrexate will be enrolled from around 45 to 55 sites around the world. Participants will be randomly assigned to receive 1 of 3 doses of MBS2320 (5 mg, 20 mg, or 40 mg) or placebo (a "dummy" drug).

The maximum duration of study participation for a participant will be 22 weeks, which consists of a Screening Period of up to 4 weeks, Treatment Period of 12 weeks, and a Follow-up Period of 6 weeks.

Participants on the study will be asked to attend the hospital or clinic for regular visits during which they will have planned study assessments to evaluate the effectiveness, tolerability and safety of the study drug.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: MBS2320 5 mg; Drug: MBS2320 20 mg; Drug: MBS2320 40 mg

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina
    • Site 1201 - Univerzitetski Klinicki Centar Republike Srpske
  • Banja Luka, Bosnia and Herzegovina
    • Site 1204 - Univerzitetski Klinicki Centar Republike Srpske
  • Gradiška, Bosnia and Herzegovina
    • Site 1202 - General Hospital Gradiška
• Bulgaria
  • Pleven, Bulgaria
    • Site 1308 - Medical Center Medconsult Pleven OOD
  • Plovdiv, Bulgaria
    • Site 1302 - Medical Center Artmed OOD
  • Sofia, Bulgaria
    • Site 1303 - Diagnostic and Consulting Center Aleksandrovska EOOD
  • Sofia, Bulgaria
    • Site 1306 - Diagnostic- Consultative Center Convex EOOD
  • Sofia, Bulgaria
    • Site 1307 - Medical Center Excelsior OOD - PPDS
  • Stara Zagora, Bulgaria
    • Site 1301 - University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
  • Varna, Bulgaria
    • Site 1304 - Medical Center Leo Clinic EOOD, Varna
• Chile
  • Providencia, Chile
    • Site 2103 - Enroll SpA - PPDS
  • Providencia, Chile
    • Site 2105 - CTR Estudios
  • Santiago, Chile
    • Site 2104 - Meditek Ltda
  • Santiago, Chile
    • Site 2106 - Biocinetic SpA
  • Santiago, Chile
    • Site 2107 - Hospital Dr Sotero Del Rio
  • Valdivia, Chile
    • Site 2102 - Clinical Research Chile SpA - PPDS
  • Viña del Mar, Chile
    • Site 2101 - Oncocentro APYS
• Czechia
  • Ostrava, Czechia
    • Site 1104 - CCR Ostrava s.r.o.
  • Pardubice, Czechia
    • Site 1101 - CCR Czech
  • Prague, Czechia
    • Site 1103 - CLINTRIAL s.r.o.
  • Uherské Hradište, Czechia
    • Site 1102 - MEDICAL PLUS, s.r.o.
• Guatemala
  • Guatemala, Guatemala
    • Site 2401 - Clinica Medica Con Especialidad Reumatologia
  • Guatemala, Guatemala
    • Site 2402 - Clinica Medica Especializada en Reumatologia
  • Guatemala, Guatemala
    • Site 2404 - Reumacentro
  • Guatemala, Guatemala
    • Site 2405 - Hospital Herrera Llerandi
  • Guatemala, Guatemala
    • Site 2406 - Clinica Medica Especializada en Medicina Interna
• Mexico
  • Burócratas del Estado, Mexico
    • Site 2206 - Centro de Alta Especialidad En Reumatologia E Investigacion Del Potosi SC
  • Guadalajara, Mexico
    • Site 2203 - Centro de Estudios de Investigacion Basica Y Clinica SC
  • León, Mexico
    • Site 2202 - Morales Vargas Centro de Investigacion SC
  • Mexicali, Mexico
    • Site 2201 - Centro de Investigación en Artritis y Osteoporosis - PPDS
  • Mexico City, Mexico
    • Site 2205 - Biológicos Especializados S.A. de C.V.
  • Miguel Hidalgo, Mexico
    • Site 2204 - Centro de Investigación y Tratamiento Reumatológico S.C
• Poland
  • Bialystok, Poland
    • Site 1006 - ClinicMed Daniluk, Nowak Spółka Jawna
  • Bydgoszcz, Poland
    • Site 1002 - MICS Centrum Medyczne Bydgoszcz
  • Bydgoszcz, Poland
    • Site 1009 - Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
  • Nadarzyn, Poland
    • Site 1007 - NZOZ Lecznica MAK-MED
  • Nowa Sól, Poland
    • Site 1004 -Twoja Przychodnia NCM
  • Olsztyn, Poland
    • Site 1001 - ETYKA Osrodek Badan Klinicznych
  • Warszawa, Poland
    • Site 1003 - Centrum Medyczne Reuma Park NZOZ
  • Warszawa, Poland
    • Site 1008 - Centrum Medyczne AMED
• Serbia
  • Belgrade, Serbia
    • Site 1402 - Institute of Rheumatology Belgrade - PPDS
  • Belgrade, Serbia
    • Site 1403 - Institute of Rheumatology Belgrade - PPDS
  • Belgrade, Serbia
    • Site 1404 - Military Medical Academy
  • Belgrade, Serbia
    • Site 1405 - Institute of Rheumatology Belgrade - PPDS
  • Niška Banja, Serbia
    • Site 1406 - Institute for Treatment and Rehabilitation Niska Banja
  • Novi Sad, Serbia
    • Site 1401 - Special Hospital For Rheumatic Diseases Novi Sad

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with RA based on either the 1987-revised ACR classification criteria or the 2010 ACR/ EULAR criteria for ≥3 months prior to screening.

2. Has active RA as defined by the following minimum disease activity criteria:

   • ≥6 swollen joints (based on 66 joint counts)
   • ≥6 tender joints (based on 68 joint counts)
   • hsCRP > upper limit of normal reference range (ULN)
3. Considered to be inadequately responding to oral or parenteral MTX therapy for ≥3 months and <10 years prior to screening and to be tolerating a dose of 15 to 25 mg per week. Participants should also be on a stable dose of folic acid (or equivalent).
4. Except for MTX, must have discontinued all oral DMARDs prior to baseline visit.
5. If participants are taking NSAIDs or acetaminophen for stable medical conditions, they should be receiving these medications at a stable dose for at least 4 weeks prior to baseline visit and the doses of the medications should be kept stable throughout the study.
6. If participants are taking oral corticosteroids (equivalent to prednisolone ≤10 mg), or inhaled corticosteroids, they should be receiving these medications at a stable dose for at least 4 weeks prior to baseline visit for stable medical conditions.

This list contains only key inclusion criteria.

Exclusion Criteria:

1. Abnormality in the 12-lead ECG, heart rate or blood pressure at screening.
2. Any clinically significant neurological, GI, renal, hepatic, CV, psychiatric, respiratory, metabolic, endocrine, haematological, ophthalmic, or other major disorder which, in the opinion of the Investigator, would put the participant at risk by participating in the study.
3. Any current malignancy or a history of malignancy within 5 years prior to screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
4. Any other inflammatory or arthritic disease in addition to RA that may interfere with the study.
5. Active infection that is clinically significant in the Investigator's opinion, or any infection requiring hospitalisation or treatment with intravenous antimicrobials ≤60 days of screening, or any infection requiring oral antimicrobial therapy ≤2 weeks of the baseline visit.
6. Clinically significant features of arthroses that could interfer with study assessments and objectives.

This list contains only key exclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral capsule
Experimental: MBS2320 5 mg	Drug: MBS2320 5 mg; Oral capsule
Experimental: MBS2320 20 mg	Drug: MBS2320 20 mg; Oral capsule
Experimental: MBS2320 40 mg	Drug: MBS2320 40 mg; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving a successful composite clinical response according to the criteria for American College of Rheumatology 20% response (ACR20)	Achieving clinical response according to the criteria for ACR20: ≥20% improvement in 68-Tender Joint Count;; ≥20% improvement in 66-SJC; and; ≥20% improvement in at least 3 of the 5 following parameters:Physician's global assessment of disease activityParticipant's global assessment of disease activityParticipant's assessment of arthritis painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP)	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving clinical response according to the criteria for American College of Rheumatology 50% response (ACR50)	Achieving clinical response according to the criteria for ACR50: ≥50% improvement in 68-Tender Joint Count;; ≥50% improvement in 66-SJC; and; ≥50% improvement in at least 3 of the 5 following parameters:Physician's global assessment of disease activityParticipant's global assessment of disease activityParticipant's assessment of arthritis painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP)	Week 12
Percentage of participants achieving clinical response according to the criteria for American College of Rheumatology 70% response (ACR70)	Achieving clinical response according to the criteria for ACR70: ≥70% improvement in 68-Tender Joint Count;; ≥70% improvement in 66-SJC; and; ≥70% improvement in at least 3 of the 5 following parameters:Physician's global assessment of disease activityParticipant's global assessment of disease activityParticipant's assessment of arthritis painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP)	Week 12
Percentage of participants achieving DAS28-hsCRP remission	Difference in mean change from baseline in DAS28-hsCRP. DAS28-hsCRP is a composite score that includes 4 variables: tender and swollen joint counts (based on 28 joints each), participant's global assessment of disease activity, and hsCRP.	Week 12
Safety and tolerability of MBS2320	Incidence of all grade adverse events	Week 12
Change in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores	Difference in mean change from baseline in each RAMRIS score (synovitis, bone oedema, and bone erosion scores measured with MRI).	Week 12
Change in cartilage loss (CARLOS) scores	Change in cartilage loss in the hand and wrist from baseline measured with MRI and scored using a validated 9-point scale with 0.5 increments where 0.0 is no cartilage loss and 4.0 is complete ankylosis.	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady state plasma concentration of MBS2320	Plasma concentration of MBS2320 will be determined for each sample collected at the specified time points	Week 12

Collaborators and Investigators

• Sponsor: Modern Biosciences Ltd
• Investigators: Study Director: Eric Bouilloux, Modern Biosciences Ltd

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2022
• Primary Completion (Actual): December 28, 2023
• Study Completion (Actual): January 29, 2024

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis (RA); MBS2320
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: IST-06; 2020-005496-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No