99mTc-rhAnnexin V-128 a Phase I/IIa Study in Patients With Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS)
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|ClinicalTrials.gov Identifier: NCT02328027|
Recruitment Status : Terminated (Low recruitment)
First Posted : December 31, 2014
Results First Posted : June 9, 2020
Last Update Posted : October 8, 2020
This was a monocentric, open label, Phase I-IIa study. Eligible patients who signed the ICF received two single intravenous (IV) bolus of the imaging agent 99mTc-rhAnnexin V-128. The first dose was administered on Day 1, and the second dose on Day 42 (±2 weeks).
All patients were to start a new disease modifying treatment for RA or AS on Day 2. This disease modifying treatment was at the discretion of the investigator and was not chosen by the sponsor.
Safety was monitored at every visit. Whole body scintigraphic imaging was performed at Day 1 and Day 42 after 99mTc-rhAnnexin V-128 dosing. Clinical disease assessments were performed at screening, Day 42 and Day 90 to assess response to RA or AS treatment. Blood was drawn to test for 99mTc-rhAnnexin V-128 immunogenicity at screening and on Days 30, 56 and 90. Patients participating in the pharmacokinetic (PK)/dosimetric sub-study had additional assessments in the 24 hours following the Day 1 dose of 99mTc-rhAnnexin V-128.
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis Ankylosing Spondylitis||Drug: 99mTc-rhAnnexin V-128||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I-IIa Study of Safety, Tolerance, Pharmacokinetics, Dosimetry and Benefice of Early Nuclear Medicine Imaging of 99mTc-rhAnnexin V-128 in Patients With Rheumatoid Arthritis or Ankylosing Spondylitis|
|Actual Study Start Date :||December 11, 2014|
|Actual Primary Completion Date :||October 17, 2017|
|Actual Study Completion Date :||October 17, 2017|
Experimental: 99mTc-rhAnnexin V-128, i.v.
Patients will receive 2 administrations of the 99mTc-rhAnnexin V-128 medical imaging agent: one at Day 1 and the other at Day 42.
Drug: 99mTc-rhAnnexin V-128
1 single intravenous bolus administration of 250 MBq, at Day 1 and at Day 42.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death [ Time Frame: From screening up to Day 90 ]An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease, temporally associated with the use of a study medication, whether or not causally related to the study medication. TEAEs are defined as all AEs reported after the first dose. An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, life-threatening, results in persistent or significant disability/incapacity, results in congenital anomaly or birth defect, requires in-patient hospitalization or leads to prolongation of hospitalization.
- Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128 [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours) ]AUC is defined as area under the curve extrapolated to infinity of 99mTc-rhAnnexin V-128.
- Distribution Volume (Vz) of 99mTc-rhAnnexin V-128 [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours) ]Vz is defined as the distribution volume of 99mTc-rhAnnexin V-128.
- Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128 [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours) ]Cl is defined as the systemic clearance of 99mTc-rhAnnexin V-128.
- Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128 [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours) ]t1/2 is defined as the elimination half-life of 99mTc-rhAnnexin V-128.
- Serum Concentration of rhAnnexin V-128 Based on Enzyme-linked Immunosorbent Assay (ELISA) Analysis [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 24.00 hours) ]Serum concentration of rhAnnexin V-128 based on ELISA analysis were to be evaluated and reported overtime.
- 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00 and 24.00 hours) ]Total radioactivity count per minute in whole blood samples were reported.
- 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) [ Time Frame: Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00, 6.00 and 24.00 hours) ]Total radioactivity count per minute in serum samples were reported.
- 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) [ Time Frame: Day 1 (0 (Predose), 1.00, 4.00, 6.00 and 24.00 hours) ]Total radioactivity count per minute in urine samples were reported.
- Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis [ Time Frame: Day 1 (0 (Predose), up to 1.00 hour, from 1.00 to 4.00 hours, from 4.00 to 6.00 hours, from 16.00 to 24.00 hours) ]Urine samples (10 mL aliquots) were analysed as a function of time by SEC-HPLC technique at the local laboratory in order to gain information on the chemical status of 99mTc-rhAnnexin V-128 and on the presence of 99mTc-rhAnnexin V-128-related species.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02328027
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Vaud, Switzerland, 1011|
|Principal Investigator:||John Prior, MD, PhD||CHUV Lausanne|
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|