Impact of Concomitant MTX on Efficacy, Safety and Adherence of Ustekinumab-treatment in Patients With Active PsA

NCT03148860 | Completed Phase 3 DMC

• 1 other identifier: TMP-1115_01
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief Summary

Methotrexate (MTX) co-medication can improve the therapeutic effect of biological therapies (e.g. Tumor necrosis factor (TNF) -inhibitors) in rheumatoid arthritis (RA), but its role in Psoriatic Arthritis (PsA) remains unclear. No data from Randomized Clinical Trials (RCTs) are available to address the questions whether add-on of MTX to UST monotherapy, or a withdrawal of continuous MTX therapy in patients with newly initiated Ustekinumab (UST) treatment or simultaneously induction of MTX with UST in naive active PsA-patients will influence outcome measurements. So, the purpose of the study is to analyse the effects of blinded MTX-co-medication on outcome in patients treated with UST: Non-inferiority at week 24 of UST monotherapy compared to add-on to MTX in patients with active PsA and at least 12 weeks of MTX treatment prior to screening or who are actually not treated with MTX and do not have prior inadequate response to MTX-treatment for PsA will be demonstrated.

Conditions

Psoriatic Arthritis

Keywords

Psoriatic Arthritis; Ustekinumab; Methotrexate; DAS28

Outcome Measures

Primary Outcomes (1)

• Assessment of mean values of DAS28 at week 24

  To demonstrate non-inferiority of mean values of DAS28 at week 24 of UST monotherapy compared to add-on to MTX with stratification according to patients on or without MTX before randomization.

  week 24

Secondary Outcomes (68)

• Assessment of mean DAS28 at week 52

  week 52

• Assessment of DAS28

  week 4

• Assessment of DAS28

  week 16

• Assessment of DAS28

  week 24

• Assessment of DAS28

  week 40

Study Arms (4)

Methotrexate naive - Ustekinumab and Methotrexate

ACTIVE COMPARATOR

Methotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

Drug: Methotrexate; Drug: Ustekinumab

Methotrexate naive - Ustekinumab and Placebo to Methotrexate

PLACEBO COMPARATOR

Methotrexate naive subjects will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

Drug: Ustekinumab; Other: Placebo

Methotrexate pre-treated subjects-Ustekinumab and Methotrexate

ACTIVE COMPARATOR

subjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

Drug: Methotrexate; Drug: Ustekinumab

Methotrexate pre-treated subjects-Ustekinumab and PLC

PLACEBO COMPARATOR

subjects pretreated with Methotrexate will be randomised to receive Methotrexate or Placebo, Ustekinumab will be given open-label

Drug: Ustekinumab; Other: Placebo

Interventions

Methotrexate DRUG

subjects will receive once weekly 15 mg (3 capsules) MTX

Methotrexate naive - Ustekinumab and Methotrexate; Methotrexate pre-treated subjects-Ustekinumab and Methotrexate

Ustekinumab DRUG

subject will receive Ustekinumab open-label over a treatment period of 52 weeks

Also known as: Stelara

Methotrexate naive - Ustekinumab and Methotrexate; Methotrexate naive - Ustekinumab and Placebo to Methotrexate; Methotrexate pre-treated subjects-Ustekinumab and Methotrexate; Methotrexate pre-treated subjects-Ustekinumab and PLC

Placebo OTHER

subjects will receive once weekly 3 capsules PLC to MTX

Methotrexate naive - Ustekinumab and Placebo to Methotrexate; Methotrexate pre-treated subjects-Ustekinumab and PLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with active psoriatic arthritis who are naïve to UST will be stratified to either without MTX-therapy or on MTX-treatment (dosage 15mg once weekly) for at least 12 weeks prior to screening.
• Active PsA is defined as TJC ≥4 and SJC ≥4 (68/66 joint count) and DAS28 ≥ 3,2 at screening
• PsA according to CASPAR criteria
• At least age of 18 years
• Presence of chest x-ray without signs of active or latent infection (esp. for tuberculosis) within the last 3 months
• Permitted pre-treatment with up to three biologic-agents, whereupon only one biologic agent must be withdrawn due to inadequate response.
• For MTX-naive patients: Previous use of NSAID
• Written informed consent obtained prior to the initiation of any protocol-required procedures
• For the group on MTX: Patients must have stable MTX dosages of at least 15mg once weekly for at least 12 weeks prior to screening and stable MTX dosages of at 15mg once weekly for at least 4 weeks prior to screening
• Compliance of intake of MTX must be documented by treating physician
• For the group without MTX therapy: patients must be eligible for MTX treatment (according to SmPC) and have not failed prior MTX treatment for the treatment of PsA

You may not qualify if:

• Previous use of UST or any other anti-IL23 agent
• according to SmPC
• \- Inadequate Response to prior MTX-treatment for Psoriatic Arthritis
• previous B-cell depleting therapy
• Patients with other chronic inflammatory articular disease or systemic autoimmune disease with musculoskeletal symptoms
• Patients with active Tb
• Patients with latent Tb, measured by Interferon gamma release assay, that are not pre-treated for at least 1 months and planned to be treated 9 months in total with INH once a day according to local guidelines
• Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms
• Primary or secondary immunodeficiency
• History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised
• Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome
• History of a severe psychological illness or condition
• Known hypersensitivity to any component of the product
• Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test
• Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier)

Sponsors & Collaborators

• Dr. Frank Behrens: lead
• Janssen-Cilag Ltd.: collaborator

Study Sites (1)

CIRI

Frankfurt am Main, Hessia, 60526, Germany

Location

Related Publications (2)

• Koehm M, Rossmanith T, Foldenauer AC, Herrmann E, Brandt-Jurgens J, Burmester GR, Kellner H, Kiltz U, Kofler DM, Rech J, Mojtahed-Poor S, Jonetzko C, Burkhardt H, Behrens F; MUST Investigator Group. Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial. Lancet Rheumatol. 2023 Jan;5(1):e14-e23. doi: 10.1016/S2665-9913(22)00329-0.

  PMID: 38251504 DERIVED

• Mojtahed Poor S, Henke M, Ulshofer T, Kohm M, Behrens F, Burkhardt H, Schiffmann S. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 Dec 1;62(12):3993-3999. doi: 10.1093/rheumatology/kead177.

  PMID: 37079726 DERIVED

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

Methotrexate; Ustekinumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Frank Behrens, MD

  Fraunhofer IME

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Methotrexate tablets will be encapsulated equal to Placebo to ensure blinding. Ustekinumab will be open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating Investigator and representative of sponsor

Model Details: randomised, placebo-controlled, double-blind, multicenter study

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: May 11, 2017
• Study Start: December 15, 2016
• Primary Completion: April 12, 2021
• Study Completion: October 21, 2021
• Last Updated: March 2, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)