Rheumatoid ArthritisPhase 3NCT05246280
Tc 99m Tilmanocept Imaging for Early Prediction of Anti-TNFα Therapy Response in Moderate to Severe Active RA
A Phase 3 study testing TC99m-tilmanocept in people with Rheumatoid Arthritis, run by Navidea Biopharmaceuticals at 13 sites in United States.
Trial summary
This study will confirm the ability of Tc 99m tilmanocept imaging to predict clinical response in individuals with RA who are beginning anti-TNFα therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- TC99m-tilmanocept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 13 sitesUnited States
- Study dates
- 2 Mar 2022to 9 Jul 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures.
- The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis.
- The subject is a candidate for initiation of, or change to, a new anti-TNFα bDMARD therapy.
- The subject has RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10).
- The subject has moderate to severe RA as determined by a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the Erythrocyte Sedimentation Rate [ESR] test and Visual Analog Scale [VAS]).
- Subjects receiving traditional DMARDs must have been on therapy for ≥ 90 days and at a stable dose for ≥ 30 days prior to the first imaging visit (Day 0).
- Subjects receiving bDMARD or janus kinase (JAK) inhibitor therapy must have been at a stable dose > 60 days prior to the first imaging visit (Day 0).
- If the subject is receiving NSAIDS (nonsteroidal anti-inflammatory drug) or oral corticosteroids, the dose has been stable for > 28 days prior to the first imaging visit (Day 0). The corticosteroid dose must be ≤ 10 mg/day of prednisone or an equivalent steroid dose.
Who cannot join
- The subject is pregnant or lactating.
- The subject size or weight is not compatible with imaging per the investigator.
- The subject is currently receiving radiation therapy or chemotherapy or has received radiation or chemotherapy within the past 5 years.
- The subject has an active malignancy or a history of malignancy within the past 5 years.
- The subject has had a finger, hand, and/or wrist amputation or hand or wrist joint arthroplasty.
- The subject has renal insufficiency as demonstrated by a glomerular filtration rate of < 60 mL/min.
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- The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase [SGPT]) or AST (aspartate aminotransferase [SGOT]) greater than 2 times the upper limit of normal.
- The subject has any severe, acute, or chronic medical conditions and/or psychiatric conditions and/or laboratory abnormalities that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration that would deem the subject inappropriate for study participation.
- The subject has a history of hypersensitivity reactions to TNF-inhibitors.
- The subject has a known allergy to or has had an adverse reaction to dextran exposure.
- The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration at the first imaging visit (Day 0).
- The subject has received intra-articular corticosteroid injections ≤ 8 weeks prior to the first imaging visit (Day 0).
- The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept at the first imaging visit (Day 0).
- The subject has heart failure [New York Heart Association (NYHA) Class III-IV], a demyelinating disorder, or a chronic/latent infection [e.g., +Purified Protein Derivative (PPD) test, Human Immunodeficiency Virus (HIV), Hepatitis B].
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Highlands Advanced Rheumatology and Arthritis Center
Avon Park, Florida, 33825
Attune Health Research
Beverly Hills, California, 90211
Believe Clinical Trials
Coral Springs, Florida, 33065
Arthritis and Osteoporosis Center of Coastal Bend
Corpus Christi, Texas, 78415
Nouvelle Clinical Research
Cutler Bay, Florida, 33189
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Vida Clinical Research
Kissimmee, Florida, 34741
Physician Research Collaboration
Lincoln, Nebraska, 68516
Life Clinical Trials
Margate, Florida, 33063
D&H National Research Centers, Inc
Miami, Florida, 33155
Advanced Clinical Research of Orlando
Ocoee, Florida, 34761
University of California, San Francisco
San Francisco, California, 94110
Essential Medical Research
Tulsa, Oklahoma, 74137
About this study
Official title: Evaluation of Tc 99m Tilmanocept Imaging for the Early Prediction of Anti-TNFα Therapy Response in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)
This study will confirm the ability of Tc 99m tilmanocept imaging to predict clinical response in individuals with RA who are beginning anti-TNFα therapy.
Read the detailed description
This is a prospective, open-label, multicenter study designed to evaluate the early predictive capacity of Tc 99m tilmanocept planar imaging for downstream clinical response(s) in individuals with moderate to severe RA who are candidates for change in anti-TNFα therapy. Temporal (Baseline to 5 week) differences in quantitative imaging will be correlated with longitudinal (Baseline to 12- and 24-week) assessments of clinical RA outcomes to evaluate the clinical utility of Tc 99m tilmanocept for the expedited evaluation of antirheumatic treatment efficacy when compared with longitudinal assessments in clinical practice.
- Conditions
- Rheumatoid Arthritis
- Being tested
- TC99m-tilmanocept
- Keywords
- RA, Tilmanocept
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TC99m-tilmanoceptDrug
Also called tilmanocept, Lymphoseek
Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface.
| Study group | Role | What they receive |
|---|---|---|
| Candidates for initiation of anti-TNFα bDMARD therapy | Experimental | All subjects will be candidates for initiation of, or change to, a new anti-TNFα bDMARD for RA treatment. Receives: Drug: TC99m-tilmanocept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Specificity of Tilmanocept Uptake Value (TUV)
Specificity of the change in TUVglobal with bucketing from baseline to 5 weeks after a change in anti-TNFα therapy (ΔTUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy.
Measured: Up to 213 days
Sensitivity of Tilmanocept Uptake Value (TUV)
Sensitivity of the change in TUVglobal with bucketing from baseline to 5 weeks after change in anti-TNFα therapy (ΔTUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy.
Measured: Up to 213 days
Secondary outcomes (13)
Negative Predictive Value (NPV) of TUV Baseline at Week 24
NPV of TUV global obtained at baseline (TUVglobal[b]) with respect to ACR50 at week 24 after change in anti-TNFα therapy
Measured: Up to 213 days
Sensitivity and Specificity of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Week 12
Concordance of ΔTUVglobal[5w] with bucketing and ACR50 at week 12, evaluated using sensitivity and specificity.
Measured: Up to 213 days
NPV, and PPV, and OA of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Weeks 12 and 24
Concordance of ΔTUVglobal[5w] (with bucketing) and clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ΔTUVglobal[5w] and the clinical criteria will be evaluated using NPV, PPV and overall accuracy.
Measured: up to 213 days
Negative Predictive Value (NPV) of TUV Baseline at Week 12
Negative predictive value (NPV) of TUVglobal obtained at baseline (TUVglobal[b]) with respect to ACR50 at week 12
Measured: up to 213 days
Concordance of TUV Baseline and Change in Clinical Disease Activity Index (CDAI), 28-joint Count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria
TUVglobal[b] and response to new anti-TNFα bDMARD therapy defined by the change from baseline (CFB) of CDAI to 12 +/- 1 weeks and 24 +/- 1 weeks, by the CFB of DAS28 to 12 +/- 1 weeks and 24 +/- 1 weeks and by the CFB in each of the ACR Response Criteria components at 12 +/- 1 weeks and at 24 +/- 1 weeks.
Measured: Up to 213 days
Concordance of TUV Baseline to Week 5 and Change in Clinical Disease Activity Index (CDAI)
ΔTUVglobal[5w] and response to new anti-TNFα bDMARD therapy defined by the CFB of CDAI to 12 +/- 1 weeks and 24 +/- 1 weeks.
Measured: Up to 213 days
Concordance of TUV Baseline to Week 5 and Clinical Disease Activity Index (CDAI),28-joint Count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria
Concordance of ΔTUVglobal[5w] (without bucketing) and clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ΔTUVglobal[5w] and the clinical criteria will be evaluated using NPV, PPV, sensitivity, specificity, and overall accuracy.
Measured: Up to 213 days
Concordance of TUV Baseline to Week 12 and Clinical Disease Activity Index (CDAI),28-joint Count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria
Concordance of ΔTUVglobal[12w] and change in clinical criteria, including ACR Response Criteria, CDAI, DAS28, and HAQ-DI©. Concordance between ΔTUVglobal[12w] and the clinical criteria will be evaluated using NPV, PPV, sensitivity, specificity, and overall accuracy.
Measured: Up to 213 days
Correlation of TUV Baseline to Week 5 and ACR Response Criteria Components
Correlation of ΔTUVglobal[5w] and response to new anti-TNFα bDMARD therapy from baseline to 24 +/- 1 weeks defined by the changes from baseline in each of the ACR Response Criteria components, including:
- Tender joint count (TJC)
- Swollen joint count (SJC)
- Patient assessment of global disease activity
- Rheumatologist assessment of global disease activity
- Patient assessment of pain
- Patient assessment of physical function
- Acute-phase reactant value
Measured: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by AEs
Incidence of AEs related to Tc 99m tilmanocept.
Measured: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in Clinical Laboratory Tests
Number of participants with changes over time in clinical laboratory tests (hematology, serum chemistry, urinalysis, and RA panel).
Measured: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in ECG Parameters
Number of participants with changes over time in ECG parameters (PRS Interval, QRS Duration, QT Interval, and QTc Interval).
Measured: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in Vital Signs
Number of participants with changes over time in vital signs (blood pressure, heart rate, respiratory rate, and temperature).
Measured: Up to 213 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2022
- Study start2 Mar 2022
- Primary completion9 Jul 2024
- Study completion9 Jul 2024
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Navidea Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Blue, MD, Study director, Navidea Biopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05246280
- Sponsor's protocol ID
- NAV3-33
- Status last verified
- Jan 2025
- First submitted
- 16 Dec 2021
- Last updated
- 23 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Tc 99m Tilmanocept Imaging for the Early Prediction of Anti-TNFα Therapy Response in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)
- ClinicalTrials.gov ID
- NCT05246280
- Acronym / sponsor ID
- NAV3-33
- Conditions
- Rheumatoid Arthritis
- Keywords
- RA, Tilmanocept
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 169 participants (actual)
- Lead sponsor
- Navidea BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2022 (actual)
- Primary completion
- 9 Jul 2024 (actual)
- Study completion
- 9 Jul 2024 (actual)
- First posted
- 18 Feb 2022 (actual)
- Results
- Posted 23 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will confirm the ability of Tc 99m tilmanocept imaging to predict clinical response in individuals with RA who are beginning anti-TNFα therapy.
Detailed description
This is a prospective, open-label, multicenter study designed to evaluate the early predictive capacity of Tc 99m tilmanocept planar imaging for downstream clinical response(s) in individuals with moderate to severe RA who are candidates for change in anti-TNFα therapy. Temporal (Baseline to 5 week) differences in quantitative imaging will be correlated with longitudinal (Baseline to 12- and 24-week) assessments of clinical RA outcomes to evaluate the clinical utility of Tc 99m tilmanocept for the expedited evaluation of antirheumatic treatment efficacy when compared with longitudinal assessments in clinical practice.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Candidates for initiation of anti-TNFα bDMARD therapy | Experimental | Drug: TC99m-tilmanoceptAll subjects will be candidates for initiation of, or change to, a new anti-TNFα bDMARD for RA treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) authorization before the initiation of any study-related procedures.
- The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis.
- The subject is a candidate for initiation of, or change to, a new anti-TNFα bDMARD therapy.
- The subject has RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10).
- The subject has moderate to severe RA as determined by a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the Erythrocyte Sedimentation Rate [ESR] test and Visual Analog Scale [VAS]).
Key exclusion criteria (14 listed)
- The subject is pregnant or lactating.
- The subject size or weight is not compatible with imaging per the investigator.
- The subject is currently receiving radiation therapy or chemotherapy or has received radiation or chemotherapy within the past 5 years.
- The subject has an active malignancy or a history of malignancy within the past 5 years.
- The subject has had a finger, hand, and/or wrist amputation or hand or wrist joint arthroplasty.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TC99m-tilmanoceptAlso: tilmanocept, LymphoseekTilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. | Drug | Candidates for initiation of anti-TNFα bDMARD therapy |
Primary outcome
Specificity of Tilmanocept Uptake Value (TUV)
Time frame: Up to 213 days
Specificity of the change in TUVglobal with bucketing from baseline to 5 weeks after a change in anti-TNFα therapy (ΔTUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy.
Sensitivity of Tilmanocept Uptake Value (TUV)
Time frame: Up to 213 days
Sensitivity of the change in TUVglobal with bucketing from baseline to 5 weeks after change in anti-TNFα therapy (ΔTUVglobal[5w] with bucketing) with respect to ACR50 at week 24 after the change in therapy.
13 secondary outcomes
Negative Predictive Value (NPV) of TUV Baseline at Week 24
Time frame: Up to 213 days
Sensitivity and Specificity of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Week 12
Time frame: Up to 213 days
NPV, and PPV, and OA of ΔTUVglobal[5w] With Bucketing With Respect to ACR50 at Weeks 12 and 24
Time frame: up to 213 days
Negative Predictive Value (NPV) of TUV Baseline at Week 12
Time frame: up to 213 days
Concordance of TUV Baseline and Change in Clinical Disease Activity Index (CDAI), 28-joint Count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria
Time frame: Up to 213 days
Concordance of TUV Baseline to Week 5 and Change in Clinical Disease Activity Index (CDAI)
Time frame: Up to 213 days
Concordance of TUV Baseline to Week 5 and Clinical Disease Activity Index (CDAI),28-joint Count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria
Time frame: Up to 213 days
Concordance of TUV Baseline to Week 12 and Clinical Disease Activity Index (CDAI),28-joint Count Disease Activity Score (DAS28), and American College of Rheumatology (ACR) Response Criteria
Time frame: Up to 213 days
Correlation of TUV Baseline to Week 5 and ACR Response Criteria Components
Time frame: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by AEs
Time frame: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in Clinical Laboratory Tests
Time frame: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in ECG Parameters
Time frame: Up to 213 days
Safety of IV-administered Tilmanocept Radiolabled With Tc 99m Assessed by Number of Participants With Changes Over Time in Vital Signs
Time frame: Up to 213 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Blue, MD study director
Navidea Biopharmaceuticals
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TC99m-tilmanocept in people with Rheumatoid Arthritis, run by Navidea Biopharmaceuticals at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Specificity of Tilmanocept Uptake Value (TUV) (time frame: Up to 213 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2025.