Clinical trial NCT04093531: Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome
Official title: Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Sjögren Syndrome
Keywords: primary sjogren syndrome
PSS
SjS
Sjogren
Ustekinumab
SS
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: Janssen, LP
First posted: 2019-09-18
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Change in The European League Against Rheumatism (EULAR) Sjogren's Syndrome Patient Reported Index (ESSPRI) Score From Baseline to Week 24
timeFrame: baseline to 24 weeks
Secondary outcomes:
measure: Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure Between Day 0 and Week 24
timeFrame: baseline to 24 weeks
measure: Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24
timeFrame: baseline to 24 weeks
measure: Total Score of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI)
timeFrame: 24 weeks.
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester
state: New York
Study officials:
affiliation: Assistant Professor of Medicine
name: Ummara Shah, MD
role: PRINCIPAL_INVESTIGATOR
References: