Back to results

99mTc-rhAnnexin V-128 a Phase I/IIa Study in Patients With Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS)

Primary Purpose

Rheumatoid Arthritis, Ankylosing Spondylitis

Status

Terminated

Phase

Phase 1

Locations

Switzerland

Study Type

Interventional

Intervention

99mTc-rhAnnexin V-128

About this trial

This is an interventional diagnostic trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Centre Hospitalier Universitaire Vaudois

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

99mTc-rhAnnexin V-128, i.v.

Arm Description

Patients will receive 2 administrations of the 99mTc-rhAnnexin V-128 medical imaging agent: one at Day 1 and the other at Day 42.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Distribution Volume (Vz) of 99mTc-rhAnnexin V-128

Vz is defined as the distribution volume of 99mTc-rhAnnexin V-128.

Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128

Cl is defined as the systemic clearance of 99mTc-rhAnnexin V-128.

Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128

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

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)

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)

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)

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

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.

Full Information

NCT ID

NCT02328027

First Posted

December 18, 2014

Last Updated

September 16, 2020

Sponsor

Advanced Accelerator Applications

1. Study Identification

Unique Protocol Identification Number

NCT02328027

Brief Title

99mTc-rhAnnexin V-128 a Phase I/IIa Study in Patients With Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS)

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Terminated

Why Stopped

Low recruitment

Study Start Date

December 11, 2014 (Actual)

Primary Completion Date

October 17, 2017 (Actual)

Study Completion Date

October 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Advanced Accelerator Applications

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis, Ankylosing Spondylitis

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

99mTc-rhAnnexin V-128, i.v.

Arm Type

Experimental

Arm Description

Patients will receive 2 administrations of the 99mTc-rhAnnexin V-128 medical imaging agent: one at Day 1 and the other at Day 42.

Intervention Type

Drug

Intervention Name(s)

99mTc-rhAnnexin V-128

Intervention Description

1 single intravenous bolus administration of 250 MBq, at Day 1 and at Day 42.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death

Description

Time Frame

From screening up to Day 90

Secondary Outcome Measure Information:

Title

Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128

Description

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)

Title

Distribution Volume (Vz) of 99mTc-rhAnnexin V-128

Description

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)

Title

Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128

Description

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)

Title

Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128

Description

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)

Title

Serum Concentration of rhAnnexin V-128 Based on Enzyme-linked Immunosorbent Assay (ELISA) Analysis

Description

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)

Title

99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)

Description

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)

Title

99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)

Description

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)

Title

99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)

Description

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)

Title

Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis

Description

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Prior, MD, PhD

Organizational Affiliation

CHUV Lausanne

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Centre Hospitalier Universitaire Vaudois

City

Lausanne

State/Province

Vaud

ZIP/Postal Code

1011

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

99mTc-rhAnnexin V-128 a Phase I/IIa Study in Patients With Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS)

We'll reach out to this number within 24 hrs