Primary Sjogren Syndrome

This is a Phase I/IIa Trial to evaluate the application of Placental Mesenchymal Stem/Stromal Cell (P-MSC) Therapy for the treatment and management of Sjogrens Syndrome.

Inclusion Criteria:

  1. Patients who are 18 years or older;
  2. Fluent in written and spoken English and in a position to provide written informed consent to participate;
  3. South East Queensland (SEQ)-based resident who is in a position to attend a 12-month follow up visit after their second dose of study treatment.
  4. Signs and symptoms of pSS (as delineated) below are not reversible following current clinical management plans;
  5. Female volunteers of child-bearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin or β-hCG) and both male and female volunteers have agreed to practice effective, reliable contraceptive regimen as described in Section 9.4.4 for the duration of this clinical trial;
  6. Have met the American-European Consensus Group (AECG) classification criteria for pSS:
     

I. Ocular symptoms – a positive response to at least one of the following questions:

  1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
  2. Do you have a recurrent sensation of sand or gravel in the eyes?
  3. Do you use tear substitutes more than three times a day?
     

II. Oral symptoms – a positive response to at least one of the following questions:

  1. Have you had a daily feeling of dry mouth for more than 3 months?
  2. Have you had recurrently or persistently swollen salivary glands as an adult?
  3. Do you frequently drink liquids to aid in swallowing dry food?
     

III. Ocular Signs – objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:

  1. Schirmer’s I test performed without anaesthesia (≤5 mm in 5 minutes);
  2. Rose Bengal score or other ocular dye score (≥4 according to van Bijsterveld’s scoring system).


IV. Histopathology – in minor salivary glands (obtained through normal appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score ≥ 1, defined as number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4mm2 of glandular tissue.

V. Salivary gland involvement – objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests:

  1. Unstimulated whole salivary flow (≤ 1.5mL in 15 minutes or ≤ 1.5 g in 15 minutes));
  2. Parotid sialography showing the presence of diffuse sialectasias (punctuate, cavitary or destructive pattern), without evidence of obstruction in major ducts;
  3. Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of tracer.


VI. Autoantibodies – presence in the serum of the following autoantibodies:

  1. Antibodies to Ro (SSA) or La (SSB) antigens, or both.

For primary SS:

In patients without any potentially associated disease, pSS may be defined as follows:

  1. The presence of any 4 of the 6 items is indicative of pSS as long as either item IV (histopathology) or VI (serology) is positive;
  2. The presence of any 3 of the four objective criteria items (i.e., items III, IV, V, VI)
  3. The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in clinical-epidemiological survey.


The definition of moderate to severe disease progression is based on the fact that in addition to ocular and oral signs and symptoms of pSS, study participants also have other systemic symptoms that affect their quality of life and have resulted in more aggressive immune suppression in the preceding 6 months to manage their disease.  Determination of pSS will be made by the PI. 


Exclusion Criteria: 
 

  1. A concurrent condition that may limit the decision-making capabilities of the participant (tissue donor) during the informed consent process;
  2. Past head and neck radiation treatment;
  3. A positive diagnosis of Human Immunodeficiency Virus (HIV) and/or Hepatitis C Virus (HCV) and/or Hepatitis B Virus (HBV) and/or Human cytomegalovirus (HCV) and/or Human T Cell Lymphotrophic Virus (HTLV-1) infection;
  4. A past diagnosis of Tuberculosis (TB) or a positive Mantoux screening test;
  5. Acquired Immune Deficiency Syndrome (AIDS);
  6. Past medical history or pre-existing lymphoma or positive screening clinical laboratory test results indicative of haematological malignancy;
  7. Past medical history or current sarcoidosis and/or amyloidosis;
  8. Acute or chronic graft versus host disease;
  9. Use of anticholinergic drugs (since a time shorter than 4-fold the T½ of the drug);
  10. Past history of solid organ or bone marrow transplantation;
  11. Women who are pregnant or lactating;
  12. Type 1 or type 2 diabetes;
  13. Past history of carcinoma not including focal squamous cell carcinoma (of skin)or basal cell carcinoma of the skin that is fully resolved following surgical or medical intervention;
  14. Known or suspected history of alcohol or drug abuse;
  15. Current smoker (known or suspected);
  16. Clinically significant medical conditions including but not limited to cardiovascular, neurological, psychiatric, renal, hepatic, haematological or endocrine abnormalities that in the PI’s opinion are uncontrolled and likely to affect the volunteer’s ability to comply with the study requirements;
  17. A genetic condition that is known to affect the connective tissue such as for example Marfan’s Syndrome or Ehlers Danlos Syndrome
  18. A past diagnosis of metabolic syndrome and/or history of grade III (morbid) obesity(BMI≥40);
  19. A history of severe allergies which has resulted in past anaphylactic incidents;
  20. A hypersensitivity reaction to the study treatment and the detection of donor-specific antibodies within 30 days of the event (clinical syndrome);
  21. Recent travel to areas where exposure to parasites or other infectious agents is highly likely;
  22. Patients who are diagnosed with secondary SS at the time of the screening visit based on the AECG consensus criteria as follows: In patients with a ‘potentially associated’ disease (for instance another well-defined connective tissue disease) the presence of item I and item II plus any 2 from among items III, IV and V may be considered as indicative of secondary SS, as per the Inclusion Criteria guidelines for SS diagnosis;
  23. Uncontrolled systemic hypertension (> 180/110 mmHg) at the screening visit;
  24. Clinically significant dysrhythmia detected from the screening visit ECG report;
  25. Clinically significant anaemia (haemoglobin <90g/L) from the screening visit haematology report;
  26. Pre-existing clotting disorders (thrombophilla), independent of pSS, including past history of deep vein thrombosis (DVT) and/or pulmonary embolism (PE);
  27. Serum Alanine Transaminase (ALT) or Aspartate Amino Transferase (AST) ≥3-fold the upper limit of normal or Bilirubin ≥ 2-fold the upper limit of normal at the screening visit;
  28. Severe renal impairment where creatinine clearance <30mL/minute at the time of the screening visit based on clinical chemistry results;
  29. Use of anti-platelet or anti-coagulant medication at the time of study treatment that in the opinion of the PI will interfere with the safety of the treatment infusion;
  30. Blood donation within 45 days preceding this trial and including blood donation during this clinical trial;
  31. IgG4-related disease (IgG4-RD);
  32. Major elective surgery scheduled during the course of active treatment administration and follow up;
  33. Concurrent enrolment in another interventional (medical or surgical) clinical trial during the course of this clinical trial (between screening and End of Study (inclusive));
  34.  Social factors likely to cause inability to complete the study.


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pSS FREQUENTLY ASKED QUESTIONS

Sjögren’s Syndrome (SS) is a chronic autoimmune disease characterised when the body’s immune system attacks its own healthy cells that produce saliva and tears. 

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pSS FREQUENTLY ASKED QUESTIONS