Not available

• Register: EUCTR
• Last refreshed on: 12 April 2021
• Main ID: EUCTR2013-004561-13-PT
• Date of registration: 07/05/2014
• Prospective Registration: Yes
• Primary sponsor: Ionis Pharmaceuticals, Inc
• Public title: Not available
• Scientific title: An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 420915 in Patients with Familial Amyloid Polyneuropathy (FAP) - ISIS 420915-CS3
• Date of first enrolment: 04/07/2014
• Target sample size: 135
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004561-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, France, Germany, Italy, New Zealand, Portugal, Spain, United Kingdom, United States

Contacts

• Name: Matt R. Buck
• Affiliation: Ionis Pharmaceuticals, Inc

• Name: Matt R. Buck
• Affiliation: Ionis Pharmaceuticals, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Completion of ISIS 420915-CS2 with the following as judged by the Investigator and Sponsor:
a. Satisfactory completion of dosing and end of treatment (EOT) efficacy assessments
b. No significant tolerability issues
c. Satisfactory compliance to the ISIS 420915-CS2 protocol requirements
2. Willingness to take vitamin A supplements
3. Satisfy one of the following:
a. Females: Non-pregnant and non-lactating; surgically sterile, postmenopausal, abstinent, or if engaged in sexual relations of childbearing potential, patient is using an acceptable contraceptive method (refer to Section 6.3.1) from the time of signing the informed consent form until at least 3 months after the last dose of ISIS 420915.
b. Males: Surgically sterile, abstinent, or if engaged in sexual relations with a female of childbearing potential, patient is utilizing an acceptable contraceptive method (refer to Section 6.3.1) during and for 3 months after the last dose of ISIS 420915.
4. Must have given written informed consent (signed and dated) and any authorization required by local law and be able to comply with all study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion criteria:
Have any new condition or worsening of existing condition that in the opinion of the Investigator or Sponsor would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Familial Amyloid Polyneuropathy
MedDRA version: 20.0 Level: LLT Classification code 10057949 Term: Familial amyloid polyneuropathy System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: Human Transthyretin Antisense Oligonucleotide
Product Code: ISIS 420915
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ISIS 420915
CAS Number: 1432726-13-0
Current Sponsor code: ISIS 420915
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of extended dosing with ISIS 420915 in patients with Familial Amyloid Polyneuropathy.

Primary end point(s): Safety Endpoints
• Adverse events
• Vital signs and weight
• Physical examination
• Clinical laboratory tests
• ECG
• Use of concomitant medication
• Ophthalmology and ERG examinations

Secondary Objective: To evaluate the efficacy of extended dosing with ISIS 420915 based on change from baseline and progression rate, if applicable, in the following measures:
• Modified Neuropathy Impairment Score +7 (mNIS+7)
• Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire:
o total score (all patients)
o symptoms domain score (Stage 1 patients)
o physical functioning/large fiber neuropathy domain score (Stage 2 patients)
• Modified body mass index (mBMI) and body mass index (BMI) • NIS, heat-pain sensory, touch-pressure sensory, nerve conduction, and heart rate to deep breathing tests (components of mNIS+7)
• Polyneuropathy disability score (PND score)
• To evaluate the pharmacodynamic (PD) effect of extended dosing with ISIS 420915 based on change from baseline in transthyretin (TTR) and retinol binding protein 4 (RBP4)
• Global longitudinal strain (GLS) by echocardiogram (ECHO)
To evaluate the plasma trough levels of ISIS 420915.

Timepoint(s) of evaluation of this end point: Through the course of the study.

Secondary Outcome(s)

Secondary end point(s): Efficacy Endpoints
• Change in the mNIS+7 score and components from baseline to Week 78 and Week 156
• Change in the NIS score and components from baseline to Y5-W52 and Y4-W52
• Change in the Norfolk QOL-DN questionnaire scores from baseline to Week 78 Week 156 and Week 52 of each subsequent year
• Change in the mBMI and BMI from baseline to Week 78 and Week 156
• Change in PND score from baseline to Week 78 Week 156 and at Week 52 of each subsequent year.
• Changes in Global longitudinal strain (GLS) by echocardiogram (ECHO)from baseline to Week 78 , Week 156 and at Week 52 of each subsequent year in the ISIS 420915-CS2 ECHO subgroup and in the Cardiomyopathy-ECHO (CM-ECHO) Set

Timepoint(s) of evaluation of this end point: Week 78 and Week 156 and at Week 52 of each subsequent year

Secondary ID(s)

ISIS420915-CS3

Source(s) of Monetary Support

Ionis Pharmaceuticals

Ethics review

Status: Approved
Approval date: 04/07/2014
Contact: