A PH I Pilot Imaging Study to Evaluate Molecular Imaging Methods in HVs and pSS Pts

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02899377
• Date of registration: 23/08/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A PH I Pilot Imaging Study to Evaluate Molecular Imaging Methods in HVs and pSS Pts
• Scientific title: A Pilot Study to Evaluate Molecular Imaging Methods in Primary Sjögren's Syndrome
• Date of first enrolment: November 18, 2016
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02899377
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Diagnostic. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- GROUP A: Healthy Volunteers Subjects for both PET/CT and MRI: Aged >=40 years
inclusive at the time of signing the informed consent.

Subjects for MRI, without PET/CT: Aged >=30 years inclusive at the time of signing the
informed consent Healthy as defined by the investigator, or medically qualified designee,
based on a medical evaluation including medical history, physical examination, and
laboratory tests.

- Group B: Primary Sjögren's Syndrome Patients Age >=30 years, at the time of signing
the informed consent. Diagnosis of pSS according to the American-European Consensus
Group criteria Baseline unstimulated salivary flow >0.0 mL/min or evidence of
glandular reserve function (stimulated baseline salivary flow >0.05 mL/min).

Systemically active disease, ESSDAI >=5 points

- All Subjects Body weight >=50 kilogram (kg) and body mass index within the range 18.5
to 35 kg/m^2 (inclusive)

Male or Female, where one of the following conditions apply:

A female subject is eligible to participate if she is not pregnant (as confirmed by a
negative serum human chorionic gonadotrophin test) at screening, and a negative urine
pregnancy test 4-7 days prior to Visit 1, on the day of Visit 1 (on each day of scanning),
on Visit 2, is not lactating, and at least one of the following conditions applies:
non-reproductive potential or reproductive potential and agrees to use contraceptive
methods listed in the protocol from 28 days prior to Visit 1 until follow up.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form.

Exclusion Criteria:

- Diagnosis of secondary Sjögren's Syndrome.

- Diagnosis of another systemic autoimmune disease, apart from pSS, including but not
limited to, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis or
systemic vasculitis. For Group B subjects, autoimmune conditions associated with pSS
(for example autoimmune thyroiditis, primary biliary cirrhosis or coeliac disease),
are not included in this exclusion, but should be described in the medical history
taken baseline. If in doubt please consult the medical monitor.

- Subjects with active life-threatening or organ-threatening effects of pSS meaning that
they may not be able to complete the study visits according to the protocol (as
determine by the investigator) (Group B).

- History of coagulation or bleeding disorders which would increase the risk of minor
salivary gland biopsy (for example, but not limited to, Hemophilia A or B, Von
Willibrand's disease, platelet function disorders; Group B).

- History of malignancy within 5 years of screening that, in the view of the
investigator, in consultation with the medical monitor if required, could confound the
results of the 18F-FDG PET/CT scan (including lymphoma associated with pSS). This does
not include cervical carcinoma in situ or non-melanoma skin malignancy that has been
treated with curative surgical treatment.

- History of unresolved acute or chronic infection that, in the view of the investigator
in consultation with the medial monitor, if required, could confound the results of
the 18F-FDG PET/CT.

- Subject with diabetes mellitus requiring insulin therapy

- Contraindications to MRI scanning (as assessed by MRI safety questionnaire).

- History of, or suffers from, claustrophobia or feel that they will be unable to lie
still in the PET or MRI scanner for a period of up to 1 to 2 hours.

- Where participation in the study would result in donation of blood or blood products
in excess of 500mL within a 56 day period.

- Previous inclusion in a research protocol involving nuclear medicine, PET or
radiological investigations, or as a result of occupational exposure with a
significant radiation burden (a significant radiation burden being defined as 10mSv in
addition to natural background radiation, in the previous 3 years including the dose
from this study). A clinical procedure where the subject received a direct benefit (eg
diagnostic test) will not be included in the calculation of exposure.

- Lack of adequate peripheral venous access for cannulation.

- Current participation in a study with an investigational product, or recent
participation within 5 half lives of discontinuation the drug, or within twice the
duration of the biological effect of the drug, whichever is longer

- Group A: Healthy volunteers Subject is unable to refrain from taking prescription or
non-prescription drugs (including vitamins and dietary or herbal supplements), within
7 days prior to Visit 1 until completion of Visit 2, unless in the opinion of the
investigator and Sponsor the medication will not interfere with the study.

- Group B: pSS subjects taking immunomodulatory treatment at screening are excluded
unless they have been on stable doses of these medicines for 6 weeks prior to
Screening/Baseline and are expected to remain on stable doses of these medications
until the Follow up visit. This would include drugs such as glucocorticoids,
immunosuppressive agents (for example, hydroxychloroquine, azathioprine, methotrexate,
mycophenolate mofetil, and biologic therapies). If in doubt, to be discussed with the
Medical Monitor.

- Group B: pSS subjects receiving treatment with anti-coagulant medications, including
but not limited to warfarin, heparin, thrombin inhibitors, and Factor Xa inhibitors,
and aspirin, unless the subjects is able to discontinue these medications one week
prior to minor salivary gland biopsy, or according to local guidelines. The treatment
may be restarted 3 days after the biopsy, or according to local guidelines.

- History of alcohol, prescription or non-prescription drug abuse which could interfere
with participation in the trial according to the protocol, or in the opinion of the
investigator impacts on the physical or mental wellbeing of the subject

- History of allergy/hypersensitivity to study medications including local anesthesia
(Group B), radio-isotopes or gadolinium-containing contrast agents (all subjects).

- Contraindications to gadolinium-containing contrast agents in accordance with product
labeling and local guidelines

- Estimated GFR (Modification of Diet in Renal Disease calculation) of less than 60
mL/min/1.73m^2 at screening.

- Platelet count below the laboratory normal range at screening, or prothrombin time
above the laboratory normal range at screening (Group B).

- Subject with


Age minimum: 30 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Autoimmune Diseases

Intervention(s)

Radiation: 11C-MET PET/CT Imaging

Procedure: Minor Salivary gland (labial) biopsy

Procedure: MRI Imaging with intravenous contrast with gadoterate meglumine

Radiation: 18F-FDG PET/CT Imaging

Primary Outcome(s)

Multi-parametric MRI Derived Parameter: Microvascular Volume Fraction [Time Frame: Visit 1: Within 6 weeks after Baseline]

SUV of Lachrymal Gland, Parotid Gland, and Submandibular Gland for 18F-FDG for pSS Participants [Time Frame: Visit 1: Within 6 weeks after Baseline]

TR Ratio for 11C- MET of Salivary Glands, Lachrymal Gland, Parotid Gland, and Submandibular Gland [Time Frame: Visit 1: Within 6 weeks after Baseline]

Tissue to Reference (TR) Ratio for 18F- FDG for pSS Participants [Time Frame: Visit 1: Within 6 weeks after Baseline]

Total Inflammatory Volume for 18F- FDG for pSS Participants at Selected Body Areas [Time Frame: Visit 1: Within 6 weeks after Baseline]

Multi-parametric MRI Derived Parameter: Exchange Rate (KTrans) [Time Frame: Visit 1: Within 6 weeks after Baseline]

Total Inflammatory Volume 11C- MET at Selected Body Areas [Time Frame: Visit 1: Within 6 weeks after Baseline]

Multi-parametric MRI Derived Parameter: Pure Diffusion Coefficient (D) [Time Frame: Visit 1: Within 6 weeks after Baseline]

Standardized Uptake Value (SUV) for 18F-FDG for pSS Participants in Selected Body Areas [Time Frame: Visit 1: Within 6 weeks after Baseline]

Multi-parametric MRI Derived Parameter: Apparent Diffusion Coefficient (ADC) [Time Frame: Visit 1: Within 6 weeks after Baseline]

TR Ratio for 11C- MET [Time Frame: Visit 1: Within 6 weeks after Baseline]

SUV of Lachrymal Gland, Parotid Gland, and Submandibular Gland for 11C-MET [Time Frame: Visit 1: Within 6 weeks after Baseline]

TR Ratio of Lachrymal Gland, Parotid Gland, and Submandibular Gland for 18F-FDG for pSS Participants [Time Frame: Visit 1: Within 6 weeks after Baseline]

SUV for 11C- MET in Selected Body Areas [Time Frame: Visit 1: Within 6 weeks after Baseline]

Secondary Outcome(s)

Net Irreversible Influx Rate Constant (Ki) From 11C-MET PET/CT [Time Frame: 0.1, 0.4, 0.6, 0.9, 1.1, 1.4, 1.6, 1.9, 2.5, 3.5, 4.5, 6.0, 8, 10, 12, 14, 17.5, 22.5, 27.5, 32.5 and 37.5 minutes post-injection]

Correlation Between Static and Dynamic Imaging Metrics in 11C-MET [Time Frame: 0.1, 0.4, 0.6, 0.9, 1.1, 1.4, 1.6, 1.9, 2.5, 3.5, 4.5, 6.0, 8, 10, 12, 14, 17.5, 22.5, 27.5, 32.5 and 37.5 minutes post-injection]

Secondary ID(s)

203818

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Quintiles, Inc.

Results

• Results available: Yes
• Date Posted: 25/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02899377