Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome

NCT04093531 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Ustekinumab for PSS
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Primary Sjögren Syndrome

Keywords

primary sjogren syndrome; PSS; SjS; Sjogren; Ustekinumab; SS

Outcome Measures

Primary Outcomes (1)

• Change in The European League Against Rheumatism (EULAR) Sjogren's Syndrome Patient Reported Index (ESSPRI) Score From Baseline to Week 24

  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 which ranges from 0- 10. Baseline ESSPRI total score will be compared to week 24, end of treatment, ESSPRI total score.

  baseline to 24 weeks

Secondary Outcomes (3)

• Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure Between Day 0 and Week 24

  baseline to 24 weeks

• Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24

  baseline to 24 weeks

• Total Score of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI)

  24 weeks.

Study Arms (1)

Ustekinumab

EXPERIMENTAL

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

Interventions

Ustekinumab DRUG

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.

Ustekinumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Rochester: lead
• Janssen, LP: collaborator

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Interventions

Ustekinumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was under enrolled and therefore not powered to show an effect.

Results Point of Contact

• Title: Ummara Shah, MD
• Organization: University of Rochester

ummara_shah@urmc.rochester.edu

585-275-1643

Study Officials

• Ummara Shah, MD

  Assistant Professor of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: September 18, 2019
• Study Start: January 15, 2020
• Primary Completion: May 11, 2022
• Study Completion: May 11, 2022
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)