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

NCT02328027 | Terminated Phase 1 Results DMC

• 2 other identifiers: 1002CAAA113A22101
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis; Ankylosing Spondylitis

Outcome Measures

Primary Outcomes (1)

• 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.

  From screening up to Day 90

Secondary Outcomes (9)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (1)

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

EXPERIMENTAL

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

Interventions

99mTc-rhAnnexin V-128 DRUG

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Advanced Accelerator Applications: lead

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Spondylitis, Ankylosing

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Ankylosis

Limitations and Caveats

The sponsor decided to terminate the study earlier than planned due to slow accrual (16 of the planned 20 patients).

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• John Prior, MD, PhD

  CHUV Lausanne

  PRINCIPAL INVESTIGATOR

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 31, 2014
• Study Start: December 11, 2014
• Primary Completion: October 17, 2017
• Study Completion: October 17, 2017
• Last Updated: October 8, 2020
• Results First Posted: June 9, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)