Musculoskeletal Ultrasound in Predicting Early Dose Titration With Tocilizumab

NCT01717859 | Completed Phase 4 Results

• 1 other identifier: ML28542
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine if a change in inflammation or baseline inflammation seen on the ultrasound is a good indicator of how rheumatoid arthritis patients respond to TCZ 4mg/kg and whether early prediction of dose escalation is possible by utilizing ultrasound inflammatory measures.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)

  34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Power Doppler scores. This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level.

  Baseline, 3 Month

Secondary Outcomes (7)

• Baseline to Month 6 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)

  Baseline, 6 Month

• Baseline to Month 3 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints

  Baseline, 3 Month

• Baseline to Month 6 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints

  Baseline, 6 Month

• Baseline to Month 3 Change in DAS28/ESR

  Baseline, 3 month

• Baseline to Month 6 Change in DAS28/ESR

  Baseline, 6 Month

Study Arms (1)

Tocilizumab

OTHER

All subjects will receive tocilizumab.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

All subjects will start at 4mg/kg. After 3 months, if DAS28 \> 3.2, dosage will be escalated to 8 mg/kg.

Also known as: Actemra

Tocilizumab

Eligibility Criteria

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

You may qualify if:

• Patients must have rheumatoid arthritis. Patients will be included in the trial based on the following criteria:
• Patient must meet 1987 American College of Rheumatology (ACR) criteria,
• Age \> 18 years of age,
• Baseline DAS28/ESR\>4.4,
• Stable concomitant DMARDs for more than 1 month (methotrexate, leflunomide, plaquenil, sulfasalazine, or no DMARDs). However, if the patient is not on DMARD, history of DMARD use required.
• If not on DMARD (and the patient satisfies the above statement), the patient can opt for monotherapy with tocilizumab or combination therapy OR
• If on biologic monotherapy, can opt for monotherapy with tocilizumab or DMARD combination therapy (ie. patients cannot be on biologic with TCZ)
• \) Power Doppler score of \>10 at screening.
• General Medical Concerns:
• Normal organ function, except if abnormal due to the disease under investigation
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
• Subject has provided written informed consent.

You may not qualify if:

• A patient will be excluded if the answer to any of the following statements is "yes".
• General:
• Major surgery (including joint surgery) within 8 weeks prior to baseline or planned major surgery within 6 months after baseline.
• Excluded Previous or Concomitant Therapy:
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of baseline.
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3.
• Previous treatment with anti-CD19 and anti-CD20 within 6 months of start of the study.
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.
• Previous treatment with TCZ.
• Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
• Use of prednisone \> 10mg at baseline.
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)
• Current liver disease as determined by principal investigator unless related to primary disease under investigation

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UCLA David Geffen School of Medicine, Division of Rheumatology

Los Angeles, California, 90095, United States

Location

Related Publications (4)

• Charles-Schoeman C, Wang J, Shahbazian A, Wilhalme H, Brook J, Kaeley GS, Oganesian B, Ben-Artzi A, Elashoff DA, Ranganath VK. Power doppler ultrasound signal predicts abnormal HDL function in patients with rheumatoid arthritis. Rheumatol Int. 2023 Jun;43(6):1041-1053. doi: 10.1007/s00296-023-05285-7. Epub 2023 Feb 24.

  PMID: 36828925 DERIVED

• Morris NT, Brook J, Ben-Artzi A, Martin W, Kermani TA, Avedikian-Tatosyan L, Karpouzas G, Nagam H, Navarro G, Choi S, Taylor MB, Elashoff D, Kaeley GS, Ranganath VK. Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients. Clin Rheumatol. 2021 Dec;40(12):5055-5065. doi: 10.1007/s10067-021-05857-7. Epub 2021 Jul 16.

  PMID: 34269927 DERIVED

• Kuo D, Morris NT, Kaeley GS, Ben-Artzi A, Brook J, Elashoff DA, Ranganath VK. Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy. Clin Rheumatol. 2021 Mar;40(3):1077-1084. doi: 10.1007/s10067-020-05340-9. Epub 2020 Aug 15.

  PMID: 32803573 DERIVED

• Choate EA, Kaeley GS, Brook J, Altman RD, FitzGerald JD, Floegel-Shetty AR, Elashoff DA, Ranganath VK. Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoid arthritis patients. BMC Rheumatol. 2020 Feb 3;4:8. doi: 10.1186/s41927-019-0107-2. eCollection 2020.

  PMID: 32025629 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Veena K. Ranganath
• Organization: UCLA

vranganath@mednet.ucla.edu

310-825-4321

Study Officials

• Veena Ranganath, MD, MS

  UCLA David Geffen School of Medicine, Division of Rheumatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., M.S., Assistant Clinical Professor

Study Record Dates

• First Submitted: October 19, 2012
• First Posted: October 31, 2012
• Study Start: September 1, 2014
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: May 15, 2019
• Results First Posted: November 29, 2018

Record last verified: 2019-05

Locations

US (1)