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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05460832
• Other study ID #: IST-06
• Secondary ID: 2020-005496-13
• Status: Completed
• Phase: Phase 2
• Start date: August 29, 2022
• Est. completion date: January 29, 2024

Study information

• Verified date: January 2024
• Source: Modern Biosciences Ltd
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: January 29, 2024
• Est. primary completion date: December 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MBS2320 5 mg
Oral capsule
• MBS2320 20 mg
Oral capsule
• MBS2320 40 mg
Oral capsule
• Placebo
Oral capsule

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Modern Biosciences Ltd

Countries where clinical trial is conducted

Bosnia and Herzegovina,  Bulgaria,  Chile,  Czechia,  Guatemala,  Mexico,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Steady state plasma concentration of MBS2320	Plasma concentration of MBS2320 will be determined for each sample collected at the specified time points	Week 12
Primary	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 activity; Participant's global assessment of disease activity; Participant's assessment of arthritis pain; Health Assessment Questionnaire - Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Week 12
Secondary	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
Secondary	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 activity; Participant's global assessment of disease activity; Participant's assessment of arthritis pain; Health Assessment Questionnaire - Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Week 12
Secondary	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 activity; Participant's global assessment of disease activity; Participant's assessment of arthritis pain; Health Assessment Questionnaire - Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Week 12
Secondary	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
Secondary	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
Secondary	Safety and tolerability of MBS2320	Incidence of all grade adverse events	Week 12