Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04093531
Recruitment Status : Recruiting
First Posted : September 18, 2019
Last Update Posted : March 5, 2021
Sponsor:
Information provided by (Responsible Party):
Ummara Shah, University of Rochester

Brief Summary:
This pilot study will make a preliminary determination of the safety of ustekinumab in patients with Primary Sjogren's Syndrome (PSS) and assess the response of systemic measures of inflammation (biomarkers).

Condition or disease Intervention/treatment Phase
Primary Sjögren Syndrome Drug: Ustekinumab Phase 1

Detailed Description:
This is a single-center, open label, pilot trial of ustekinumab in patients with Primary Sjögren's Syndrome (PSS). Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome
Actual Study Start Date : January 15, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ustekinumab

Arm Intervention/treatment
Experimental: Ustekinumab
All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel.
Drug: Ustekinumab
Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.




Primary Outcome Measures :
  1. Change in The European League Against Rheumatism (EULAR) Sjogren's Syndrome Patient Reported Index (ESSPRI) score from Baseline to Week 24 [ Time Frame: 24 weeks ]
    The primary endpoint is a well-established, patient reported questionnaire for use in PSS, the ESSPRI. The ESSPRI is composed of 3 scales - dryness, fatigue, and pain. Each scale is measured 0 - 10, 0 being no symptoms, 10 being maximal imaginable dryness, fatigue or pain. The total score is the mean score of the three scales. Baseline ESSPRI total score will be compared to week 24, end of treatment, ESSPRI total score.


Secondary Outcome Measures :
  1. Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure between day 0 and week 24 [ Time Frame: 24 weeks ]
    The SF-36 is a measure of health-related quality-of-life. It's a 36-item patient-reported questionnaire that covers 8 health domains. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. Changes in total scores in each domain from BL to week 24 will be measured.

  2. Change in serum biomarkers of inflammation from baseline to week 24 [ Time Frame: 24 weeks ]
    To determine whether the standard dosing schedule for ustekinumab lowers serum biomarkers of inflammation in patients with PSS blood will be collected at baseline, week 12 and week 24 for the following mechanistic studies: Serum levels of TNFα, IL-6, IL17, IL17A, IL17F, IL22, IL12, IL23, BAFF, B and T cell, blood interferon signature. Means, medians, standard deviations, minimums and maximums will be computed for each continuous mechanistic endpoint.

  3. Number of participants with treatment-emergent adverse events as defined by ICH definition of AE. [ Time Frame: 24 weeks ]
    Safety of ustekinumab in PSS patients will be measured by incidence of serious and non-serious adverse events per ICH definitions from prior to treatment and after the first dose of study drug. Number of events and number (%) of participants experiencing events will be summarized by system organ class and preferred term for each. In addition, AEs will be summarized by maximum severity and relationship to study drug.

  4. Change in total score of the EULAR Sjogren's syndrome disease activity index (ESSDAI) from baseline to week 24. [ Time Frame: 24 weeks. ]
    The ESSDAI is a disease activity measurement that has 12 domains. The score of each domain is the product of the weight of the domain by the level of activity. Activity levels are 0 - 3, 0 being no activity, 3 being high activity. The total score is the sum of the score of all domains. Change in total score from BL to week 24 will be measured.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

A subject who has met all of the following criteria is eligible for participation in the study:

  • Has provided written informed consent
  • Between the ages of 18-75 years (inclusive)
  • Body weight ≥ 40 kg
  • Meets the 2016 ACR EULAR criteria (score >4)

    • 3 points- Labial salivary gland with focal lymphocytic sialadenitis and focus score of >1 foci/4 mm2‡
    • 3 Points- Anti-SSA/Ro positive
    • 1 Point- Ocular Staining Score >5 in at least 1 eye
    • 1 Point- Schirmer's test <5 mm/5 minutes in at least 1 eye
    • 1 Point- Unstimulated whole saliva flow rate <0.1 ml/minute
  • If taking prednisone (or equivalent corticosteroid), the dose must be ≤ 10 mg/day and stable for at least 4 weeks prior to baseline visit
  • If taking hydroxychloroquine, the dose must be stable for at least 12 weeks prior to baseline.
  • If taking a cholinergic stimulant (e.g. pilocarpine, cevimeline), the dose must be stable for at least 4 weeks prior to baseline.
  • If a male of reproductive potential, must agree to practice two highly effective forms of contraception during the study (one of which must be a barrier method) and be able to continue contraception for 20 weeks after his last dose of study agent Subject must also agree not to donate sperm up to 20 weeks after his last dose of study agent.
  • If a female of childbearing potential, must agree to practice two highly effective forms of contraception during the study (one of which must be a barrier method) and able to continue contraception for 20 weeks after her last dose of study agent.

A subject who meets any of the following criteria is disqualified from participation in the study:

  • Has a chronic or persistent infection that might be worsened by immunosuppressive treatment (e.g., HIV, hepatitis B, hepatitis C, or tuberculosis).
  • History of untreated TB or positive QuantiFERON TB-Gold during screening period. If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug resistant TB infection are <5%) or active TB infection, a QuantiFERON TB-Gold test need not be obtained, but a chest radiograph or other appropriate image must still be obtained if not done so within the prior 3 months.
  • History of recurrent significant infections or occurrence of a serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within twelve weeks prior to Day 0.
  • Active symptomatic infection within two weeks prior to Day 0.
  • Receipt of live vaccine within four weeks prior to Day 0.
  • History or presence of primary or secondary immunodeficiency.
  • History of any life-threatening allergic reactions to pilocarpine or any components of ustekinumab. Pilocarpine will be used to stimulate salivary flow in order to assess flow rate.
  • Is currently pregnant or nursing.
  • Concurrent use of anticholinergic agents, such as tricyclic antidepressants, antihistamines, phenothiazines, antiparkinsonian drugs, anti-asthmatic medications, or gastrointestinal (GI) medications that cause xerostomia in more than 10% of patients.
  • Treatment with any of the following within the defined period prior to the screening and Day 0 visits:

    • 12 months for rituximab
    • 24 weeks for cyclophosphamide
    • 8 weeks for azathioprine, cyclosporine, methotrexate, and mycophenolate mofetil
    • 4 weeks for intravenous immunoglobulin
    • 4 weeks for etanercept
    • 8 weeks for adalimumab
    • 12 weeks for infliximab
    • 8 weeks Golimumab
    • 8weeks Certolizumab pegol
    • 16 weeks Abatacept
    • 4 weeks Tocilizumab SQ
    • 16 weeks Tocilizumab IV
    • 4 weeks Tofacitinib and Tofacitinib XR
  • Prednisone (or equivalent corticosteroid) > 10 mg/day.
  • A definite diagnosis of RA, SLE, systemic sclerosis, or dermatomyositis.
  • A history of alcohol or substance abuse.
  • A history of head and neck radiation therapy, sarcoidosis, or graft-versus-host disease.
  • A history of malignancy, except for a resected basal or major squamous cell carcinoma, cervical dysplasia, or in situ cervical cancer Grade I, within the last five years.
  • Abnormal laboratory results for the following parameters at the baseline visit:

    • Absolute neutrophil count (ANC): < 1500/mm3
    • Platelets: < 100,000/mm3
    • Hemoglobin: < 9 grams (g)/deciliter (dL)
    • Serum creatinine: ≥ 2.0 mg/dL
    • AST: > 1.5x upper limit of normal
    • ALT: > 1.5x upper limit of normal.
  • A psychiatric disorder rendering the subject incapable of providing informed consent.
  • Plans for foreign travel to countries other than Canada or Western Europe within the treatment period.
  • Inability or unwillingness to follow the protocol
  • Any condition or treatment that, in the opinion of the investigator, places the subject at an unacceptable risk as a participant in the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04093531


Contacts
Layout table for location contacts
Contact: Dustina Holt, MPH 585-273-5374 dustina_holt@urmc.rochester.edu

Locations
Layout table for location information
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Alena Leger    585-275-1634      
Sponsors and Collaborators
University of Rochester
Investigators
Layout table for investigator information
Principal Investigator: Ummara Shah, MD Assistant Professor of Medicine
Layout table for additonal information
Responsible Party: Ummara Shah, Assistant Professor of Medicine, University of Rochester
ClinicalTrials.gov Identifier: NCT04093531    
Other Study ID Numbers: Ustekinumab for PSS
First Posted: September 18, 2019    Key Record Dates
Last Update Posted: March 5, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Ummara Shah, University of Rochester:
primary sjogren syndrome
PSS
SjS
Sjogren
Ustekinumab
SS
Additional relevant MeSH terms:
Layout table for MeSH terms
Sjogren's Syndrome
Syndrome
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Ustekinumab
Dermatologic Agents