Clinical trial • Phase III • Rare Disease|Endocrinology

ISIS 678354 SODIUM SALT for Familial chylomicronemia syndrome (FCS)

Phase III trial of ISIS 678354 SODIUM SALT for Familial chylomicronemia syndrome (FCS). open-label, none/not specified-controlled. 30 participants.

Overview

Trial Therapeutic Area
Rare Disease|Endocrinology
Trial Disease
Familial chylomicronemia syndrome (FCS)
Trial Stage
Phase III
Drug Modality
Oligonucleotide

Key dates

Initial CTIS Submission Date
17-07-2024
First CTIS Authorization Date
12-08-2024

Trial design

open-label, none/not specified-controlled Phase III trial across 14 sites in Sweden, France, Italy and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
30
Trial Duration For Participant
1463

Eligibility

Recruits 30 Vulnerable population selected (isVulnerablePopulationSelected = true). Informed consent will be obtained using subject information sheets and informed consent forms (L1 ICF documents) provided in country-specific versions and multiple languages (examples in the record include English, Spanish, French, Italian, Dutch, Portuguese, Swedish, Slovak)..

Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Informed consent will be obtained using subject information sheets and informed consent forms (L1 ICF documents) provided in country-specific versions and multiple languages (examples in the record include English, Spanish, French, Italian, Dutch, Portuguese, Swedish, Slovak).

Inclusion criteria

  • {"criterion_text":"- Satisfactory completion of the ISIS 678354 CS3 index study (last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement"}
  • {"criterion_text":"- Willing to follow a diet comprising ≤ 20 g fat per day during the study"}

Exclusion criteria

  • {"criterion_text":"- Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary objective is to evaluate safety and tolerability of treatment with olezarsen","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Percent change in fasting TG from Baseline at Month 6 (average of Weeks 23, 25 and 27)","definition_or_measurement_approach":"Percent change in fasting TG from Baseline at Month 6 (average of Weeks 23, 25 and 27)"}
  • {"endpoint_text":"- Percent change in fasting TG from Baseline at Month 12 (average of Week 51 and 53), Month 24 (average of Week 103 and Week 105) and Month 36 (average of Week 155 and Week 157), and Month 48 (average of Week 205 and 209)","definition_or_measurement_approach":"Percent change in fasting TG from Baseline at specified months using averages of specified weeks (Month 12: Weeks 51 & 53; Month 24: Weeks 103 & 105; Month 36: Weeks 155 & 157; Month 48: Weeks 205 & 209)"}
  • {"endpoint_text":"- Proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Proportion of patients with ≥40% reduction in fasting TG from Baseline measured at Months 6, 12, 24, 36 and 48"}
  • {"endpoint_text":"- Percent change in fasting apoB48 from Baseline at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Percent change in fasting apoB48 from Baseline measured at Months 6, 12, 24, 36 and 48"}
  • {"endpoint_text":"- Percent change in fasting apoC-III from Baseline at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Percent change in fasting apoC-III from Baseline measured at Months 6, 12, 24, 36 and 48"}
  • {"endpoint_text":"- Percent change in fasting non-HDL from Baseline at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Percent change in fasting non-HDL-C from Baseline measured at Months 6, 12, 24, 36 and 48"}
  • {"endpoint_text":"- Proportion of patients who achieve fasting TG 880mg/dL at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Proportion of patients achieving fasting TG ≤ 880 mg/dL at Months 6, 12, 24, 36 and 48"}
  • {"endpoint_text":"- Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105, 157 or 209)","definition_or_measurement_approach":"Adjudicated acute pancreatitis event rate during the Treatment Period defined across Weeks 1 through 53, 105, 157 or 209"}
  • {"endpoint_text":"- Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105 157 or 209), in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to treatment with study drug in the index study","definition_or_measurement_approach":"Adjudicated acute pancreatitis event rate during Treatment Period (Weeks 1–53/105/157/209) in the subgroup with ≥2 adjudicated acute pancreatitis events in the 5 years prior to index-study treatment"}
  • {"endpoint_text":"- Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53, 105 157 or 209) in patient with a prior history of pancreatitis within 10 years prior to Screening in the index study","definition_or_measurement_approach":"Adjudicated acute pancreatitis event rate during Treatment Period (Weeks 1–53/105/157/209) in patients with prior history of pancreatitis within 10 years prior to screening in the index study"}
  • {"endpoint_text":"- Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Proportion of patients with ≥70% reduction in fasting TG from Baseline measured at Months 6, 12, 24, 36 and 48"}
  • {"endpoint_text":"- Proportion of patients who achieve fasting TG ≤ 500 mg/dL at Month 6, 12, 24, 36, 48","definition_or_measurement_approach":"Proportion of patients achieving fasting TG ≤ 500 mg/dL at Months 6, 12, 24, 36 and 48"}

Recruitment

Planned Sample Size
30
Recruitment Window Months
50
Consent Approach
Informed consent obtained using subject information sheets and informed consent forms (L1 ICF documents). Country-specific ICFs and language versions are provided (documents listed include versions in English, Spanish, French, Italian, Dutch, Portuguese, Swedish, Slovak). A pregnant partner ICF and other ancillary subject information materials are also listed.

Geography

Total Number Of Sites
14
Total Number Of Participants
30

Sweden

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
12-08-2024
Processing Time Days
5
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Molecular and Clinical Medicine
Principal Investigator Name
Stefano Romeo
Principal Investigator Email
stefano.romeo@wlab.gu.se
Contact Person Name
Stefano Romeo
Contact Person Email
stefano.romeo@wlab.gu.se

France

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
26-09-2024
Processing Time Days
50
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Endrocrinilogy
Principal Investigator Name
Bruno Verges
Principal Investigator Email
bruno.verges@chu-dijon.fr
Contact Person Name
Bruno Verges
Contact Person Email
bruno.verges@chu-dijon.fr
Site Name
Hospices Civils De Lyon
Department Name
Endrocrinology
Principal Investigator Name
Sybil Charriere
Principal Investigator Email
sybil.charriere@chu-lyon.fr
Contact Person Name
Sybil Charriere
Contact Person Email
sybil.charriere@chu-lyon.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Nutrition, metabolic diseases and endocrinology
Principal Investigator Name
René Valero
Principal Investigator Email
rene.valero@ap-hm.fr
Contact Person Name
René Valero
Contact Person Email
rene.valero@ap-hm.fr

Italy

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
02-09-2024
Processing Time Days
26
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Metabolic Diseases
Principal Investigator Name
Marcello Arca
Principal Investigator Email
marcello.arca@uniroma1.it
Contact Person Name
Marcello Arca
Contact Person Email
marcello.arca@uniroma1.it
Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
Internal Medicine
Principal Investigator Name
Angelo Baldassarre Cefalù
Principal Investigator Email
abaldassare.cefalu@unipa.it
Contact Person Name
Angelo Baldassarre Cefalù
Contact Person Email
abaldassare.cefalu@unipa.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Internal Medicine
Principal Investigator Name
Matteo Di Minno
Principal Investigator Email
matteo.diminno@unina.it
Contact Person Name
Matteo Di Minno
Contact Person Email
matteo.diminno@unina.it

Spain

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
12-08-2024
Processing Time Days
5
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Internal Medicine
Principal Investigator Name
Agustín Blanco Echevarría
Principal Investigator Email
agustin.blanco@salud.madrid.org
Contact Person Name
Agustín Blanco Echevarría
Site Name
Hospital Clinic De Barcelona
Department Name
Endocrinology and Nutrition
Principal Investigator Name
Amanda Jiménez Pineda
Principal Investigator Email
ajimenez1@clinic.cat
Contact Person Name
Amanda Jiménez Pineda
Contact Person Email
ajimenez1@clinic.cat
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Internal Medicine
Principal Investigator Name
Ovidio Muñiz Grijalvo
Principal Investigator Email
cmunizg@gmail.com
Contact Person Name
Ovidio Muñiz Grijalvo
Contact Person Email
cmunizg@gmail.com

Slovakia

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
14-08-2024
Processing Time Days
7
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Metabolické centrum Kataríny Rašlovej s.r.o.
Department Name
Ambulancia diabetológie a porúch látkovej premeny a výživy
Principal Investigator Name
Katarína Rašlová
Principal Investigator Email
metabolickecentrum@yahoo.com
Contact Person Name
Katarína Rašlová
Contact Person Email
metabolickecentrum@yahoo.com

Portugal

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
16-08-2024
Processing Time Days
9
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Unidade Local De Saude Do Alto Ave E.P.E.
Department Name
Serviço de Gastrenterologia
Principal Investigator Name
Tiago Cúrdia Gonçalves
Contact Person Name
Tiago Cúrdia Gonçalves
Site Name
Unidade Local De Saude De Lisboa Ocidental E.P.E.
Department Name
Serviço de Endocrinologia
Principal Investigator Name
João Sequeira Duarte
Principal Investigator Email
jmsduarte@chlo.min-saude.pt
Contact Person Name
João Sequeira Duarte
Contact Person Email
jmsduarte@chlo.min-saude.pt

Netherlands

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
13-08-2024
Processing Time Days
6
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Stichting Amsterdam UMC
Department Name
Vascular Medicine
Principal Investigator Name
Erik Sjoerd Gerard Stroes
Principal Investigator Email
e.s.stroes@amsterdamumc.nl
Contact Person Name
Erik Sjoerd Gerard Stroes
Contact Person Email
e.s.stroes@amsterdamumc.nl

Sponsor

Primary sponsor

Full Name
Ionis Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Pharmaceutical Product Development LLC
Responsibilities
code:4
Name
Medpace Finland Oy
Responsibilities
codes:1,10,12,13,15 (Maintenance of QA and QC of CRO systems and processes),2,4,5,8
Name
Almac Clinical Services Limited
Responsibilities
code:15 (Qualifed Person release of IMP)
Name
Bioclinica Inc.
Responsibilities
code:7
Name
Charles River Laboratories Montreal ULC
Responsibilities
code:4
Name
Versiti Wisconsin Inc.
Responsibilities
code:4

Third parties

  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes:1,10,12,13,15 (Maintenance of QA and QC of CRO systems and processes),2,4,5,8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Versiti Wisconsin Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Switzerland","full_name":"Socar Research S.A.","duties_or_roles":"code:15 (Pancreatitis and MACE Adjudication Committee (PAC))","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Accellacare Limited","duties_or_roles":"code:15 (Home health)","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"code:15 (Qualifed Person release of IMP)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"code:7","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
ISIS 678354
Active Substance
ISIS 678354 SODIUM SALT
Modality
Oligonucleotide
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Maximum Dose
50 mg
Investigational Product Name
ISIS 678354
Active Substance
ISIS 678354 SODIUM SALT
Modality
Oligonucleotide
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Maximum Dose
80 mg
Investigational Product Name
ISIS 678354
Active Substance
ISIS 678354 SODIUM SALT
Modality
Oligonucleotide
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Maximum Dose
80 mg

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