Ankylosing Spondylitis, Rheumatoid Arthritis
Conditions
Brief summary
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.
Detailed description
The study was terminated early after the inclusion of 16 of the 20 planned patients. The sponsor decided to terminate the study earlier than planned due to slow accrual. Novartis acquired Advanced Accelerator Applications SA.
Interventions
1 single intravenous bolus administration of 250 MBq, at Day 1 and at Day 42.
Sponsors
Advanced Accelerator Applications
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with RA based on ACR/EULAR 2010 criteria (score \>=6), or Patients diagnosed with AS based on the ASAS criteria. Patients with RA must have serology assessment performed and documented at the time of enrollment. * Patient with RA active disease (DAS \> 2,6) and the introduction of a Bi-DMARD should be indicated. RA patients must have been treated with DMARD (methotrexate, leflunomide and sulfasalazine) or combination of these treatments for at least 3 months. Treatment will be pursued while on study. or RA patients must have been previously treated with Bi-DMARD before initiation of the new Bi-DMARD treatment. The non-response of the previous Bi-DMARD treatment must be documented. or Patients with AS with insufficiently controlled disease while under NSAID and indication for Bi-DMARD. These patients must be under NSAID for at least 3 months and under the same NSAID for at least 1 month prior to enrollment. * ≥ 18 years old * Karnofsky ≥ 80% * Negative Pregnancy test for women with childbearing potential * For women with childbearing potential, use of two reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, associated with other barrier method of contraception such as the use of condoms) , throughout their participation in the study * Absence of ECG anomaly * written ICF signed
Exclusion criteria
* Pregnancy or lactation * Liver impairment (ALT, AST or Bilirubin \> 2 ULN) at screening visit or baseline * Kidney impairment (serum creatinine \> 1.5 mg/dL) * History of congestive heart failure (NYHA III & IV) * History of malignant disease within 5 years * History of any disease or relevant physical or psychiatric condition or abnormal physical finding which may interfere with the study objectives at the investigator judgment * Known hypersensitivity to the investigational drug or any of its components * Participation to another clinical trial within 4 weeks before study inclusion except for patients who have participated or who are currently participating in an interventional study without any study drug administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution Volume (Vz) of 99mTc-rhAnnexin V-128 | 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 | 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 | 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 | 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. |
| Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128 | 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. |
| 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 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) | 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 | 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. |
| 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 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. |
Countries
Switzerland
Participant flow
Recruitment details
It was planned that 20 evaluable patients with either RA or AS (enrolled in a 1:1 ratio) would be included and would complete the assessments on Day 56, however recruitment was terminated after inclusion of 16 patients.
Pre-assignment details
Of the 16 enrolled participants, 10 participants would take part in a PK/dosimetric sub-study, after providing written approval (only 5 participants were enrolled to the sub-study). Of the first 6 enrolled participants overall, at least 3 had to take part in the sub-study to optimise the PK time points for subsequent participants .
Participants by arm
| Arm | Count |
|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis Participants with AS received a single bolus injection of 99mTc-rhAnnexin V-128 at a dose of 250 MBq through an IV catheter in an antecubital vein, followed by a saline flush on Day 1 and on Day 42. | 5 |
| 99mTc-rhAnnexin V-128: Rheumatoid Arthritis Participants with RA received received a single bolus injection of 99mTc-rhAnnexin V-128 at a dose of 250 MBq through an IV catheter in an antecubital vein, followed by a saline flush on Day 1 and on Day 42. | 11 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128: Rheumatoid Arthritis | Total |
|---|---|---|---|
| Age, Continuous | 43.2 Years STANDARD_DEVIATION 10.73 | 51.6 Years STANDARD_DEVIATION 18.74 | 49.0 Years STANDARD_DEVIATION 16.77 |
| Race/Ethnicity, Customized Caucasian | 4 Participants | 11 Participants | 15 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Switzerland | 5 Participants | 11 Participants | 16 Participants |
| Sex: Female, Male Female | 0 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 11 |
| other Total, other adverse events | 3 / 5 | 11 / 11 |
| serious Total, serious adverse events | 0 / 5 | 1 / 11 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death
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.
Time frame: From screening up to Day 90
Population: Safety analysis set included all participants who have received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | TEAEs | 3 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | SAEs | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | Death | 0 Participants |
| 99mTc-rhAnnexin V-128: Rheumatoid Arthritis | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | TEAEs | 11 Participants |
| 99mTc-rhAnnexin V-128: Rheumatoid Arthritis | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | SAEs | 1 Participants |
| 99mTc-rhAnnexin V-128: Rheumatoid Arthritis | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death | Death | 0 Participants |
Secondary
99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Total radioactivity count per minute in whole blood samples were reported.
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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 0 (Predose) | 0.0 counts per minute (CPM) in 1 mL sample | Standard Deviation 0 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 5 min | 1667814 counts per minute (CPM) in 1 mL sample | Standard Deviation 209478 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 10 min | 1188917 counts per minute (CPM) in 1 mL sample | Standard Deviation 162265 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 15 min | 976977 counts per minute (CPM) in 1 mL sample | Standard Deviation 168240 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 30 min | 560111 counts per minute (CPM) in 1 mL sample | Standard Deviation 183995 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 1h | 270715 counts per minute (CPM) in 1 mL sample | Standard Deviation 101320 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 1.5h to 2.0h | 140730 counts per minute (CPM) in 1 mL sample | Standard Deviation 30842 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 3.0h to 4.0h | 64421 counts per minute (CPM) in 1 mL sample | Standard Deviation 20850 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 24h | 1803 counts per minute (CPM) in 1 mL sample | Standard Deviation 641 |
Secondary
99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Total radioactivity count per minute in serum samples were reported.
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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | Predose | 0.0 counts per minute (CPM) in 1 mL sample | Standard Deviation 0 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 5 min | 2043946 counts per minute (CPM) in 1 mL sample | Standard Deviation 654557 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 10 min | 1432102 counts per minute (CPM) in 1 mL sample | Standard Deviation 453282 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 15 min | 1176933 counts per minute (CPM) in 1 mL sample | Standard Deviation 299437 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 30 min | 719880 counts per minute (CPM) in 1 mL sample | Standard Deviation 287310 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 1h | 349309 counts per minute (CPM) in 1 mL sample | Standard Deviation 103963 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 1.5h to 2.0h | 223067 counts per minute (CPM) in 1 mL sample | Standard Deviation 51303 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 3.0h to 4.0h | 106070 counts per minute (CPM) in 1 mL sample | Standard Deviation 31082 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 6h | 56768 counts per minute (CPM) in 1 mL sample | — |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 24h | 3126 counts per minute (CPM) in 1 mL sample | Standard Deviation 1010 |
Secondary
99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)
Total radioactivity count per minute in urine samples were reported.
Time frame: Day 1 (0 (Predose), 1.00, 4.00, 6.00 and 24.00 hours)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 0 (Predose) | 12 counts per minute (CPM) in 1 mL sample | Standard Deviation 26 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 1 hour | 6613620 counts per minute (CPM) in 1 mL sample | Standard Deviation 1786521 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 4 hours | 9135076 counts per minute (CPM) in 1 mL sample | Standard Deviation 3248412 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 16 hours | 1517263 counts per minute (CPM) in 1 mL sample | Standard Deviation 1180019 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample) | 24 hours | 96155.2 counts per minute (CPM) in 1 mL sample | Standard Deviation 84394.79 |
Secondary
Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128
AUC is defined as area under the curve extrapolated to infinity 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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128 | Blood | 41.2 nanogram*hour per milliliter (ng.h/mL) | Standard Deviation 13.7 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128 | Serum | 53.6 nanogram*hour per milliliter (ng.h/mL) | Standard Deviation 22.6 |
Secondary
Distribution Volume (Vz) of 99mTc-rhAnnexin V-128
Vz is defined as the distribution volume 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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Distribution Volume (Vz) of 99mTc-rhAnnexin V-128 | Blood | 30.3 Liters (L) | Standard Deviation 9 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Distribution Volume (Vz) of 99mTc-rhAnnexin V-128 | Serum | 26.1 Liters (L) | Standard Deviation 11.5 |
Secondary
Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128
t1/2 is defined as the elimination half-life 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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128 | Blood | 3.6 hours | Standard Deviation 0.2 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128 | Serum | 3.8 hours | Standard Deviation 0.3 |
Secondary
Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis
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.
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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | 0 (Predose)-HPLC Performed?=Yes | Species found = No | 5 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | 0 (Predose)-HPLC Performed?=Yes | Species found = Not Specified | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | Up to 1 hour-HPLC Performed?=Yes | Species found = No | 5 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | Up to 1 hour-HPLC Performed?=Yes | Species found = Not Specified | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 1 to 4 hours-HPLC Performed?=Yes | Species found = No | 5 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 1 to 4 hours-HPLC Performed?=Yes | Species found = Not Specified | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 4 to 6 hours-HPLC Performed?=Yes | Species found = No | 5 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 4 to 6 hours-HPLC Performed?=Yes | Species found = Not Specified | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 16 to 24 hours-HPLC Performed?=Yes | Species found = No | 4 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 16 to 24 hours-HPLC Performed?=Yes | Species found = Not Specified | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 16 to 24 hours-HPLC Performed?=No | Species found = No | 0 Participants |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis | From 16 to 24 hours-HPLC Performed?=No | Species found = Not Specified | 1 Participants |
Secondary
Serum Concentration of rhAnnexin V-128 Based on Enzyme-linked Immunosorbent Assay (ELISA) Analysis
Serum concentration of rhAnnexin V-128 based on ELISA analysis were to be evaluated and reported overtime.
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)
Population: Pharmacokinetic (PK) population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Due to low concentration of the protein in serum PK parameters could not be derived.
Secondary
Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128
Cl is defined as the systemic clearance 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)
Population: PK population included all participants who participated in the PK/dosimetry sub-study which included participants regardless of their diagnosis (RA or AS). Here 'n' (number analyzed) signifies participants who were evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128 | Blood | 5.82 Liter per hour (L/h) | Standard Deviation 1.59 |
| 99mTc-rhAnnexin V-128: Ankylosing Spondylitis | Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128 | Serum | 4.68 Liter per hour (L/h) | Standard Deviation 1.67 |