JOURNAL ONKOLOGIE – STUDIE

FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04768972

Studienbeginn:
Juni 2021

Letztes Update:
08.04.2024

Wirkstoff:
ION363, Placebo

Indikation (Clinical Trials):
Sarcoma, Motor Neuron Disease, Amyotrophic Lateral Sclerosis, Sclerosis

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 3

Sponsor:
Ionis Pharmaceuticals, Inc.

Collaborator:
-

Kontakt

Ionis Pharmaceuticals
Kontakt:
Phone: (844) 421-0104
E-Mail: ionisNCT04768972study@clinicaltrialmedia.com» Kontaktdaten anzeigen

Studienlocations
(3 von 20)

Leberkrebszentrum Universitätsklinikum Ulm
Albert-Einstein-Allee 23
89081 Ulm
DeutschlandRekrutierend» Google-Maps

University of California San Diego
92037 La Jolla
United StatesRekrutierend» Google-Maps

Stanford University Medical Center
94304 Palo Alto
United StatesRekrutierend» Google-Maps

Johns Hopkins University
21205 Baltimore
United StatesRekrutierend» Google-Maps

Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps

Washington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-Maps

Columbia University Medical Center
10032 New York
United StatesRekrutierend» Google-Maps

The Ohio State University Wexner Medical Center
43210 Columbus
United StatesRekrutierend» Google-Maps

University of Utah
84132 Salt Lake City
United StatesRekrutierend» Google-Maps

UZ Leuven
3000 Leuven
BelgiumRekrutierend» Google-Maps

PSEG Centro de Pesquisa Clinica S.A.
04038-002 São Paulo
BrazilRekrutierend» Google-Maps

Montreal Neurological Institute
H3A 2B4 Montreal
CanadaRekrutierend» Google-Maps

St. James Hospital
D08 A978 Dublin
IrelandRekrutierend» Google-Maps

Citta della Salute e della Scienza di Torino - Ospedale le Molinette
10126 Torino
ItalyRekrutierend» Google-Maps

Hanyang University Seoul Hospital
4763 Seoul
Korea, Republic ofRekrutierend» Google-Maps

Universitair Medisch Centrum Utrecht
3584 CX Utrecht
NetherlandsRekrutierend» Google-Maps

University Hospital of Umea
SE-901 85 Umeå
SwedenRekrutierend» Google-Maps

Kantonsspital St. Gallen
9007 Saint Gallen
SwitzerlandRekrutierend» Google-Maps

Taipei Veterans General Hospital (VGHTP)
11217 Taipei City
TaiwanRekrutierend» Google-Maps

King's College Hospital
SE5 9RT London
United KingdomRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

This is a multi-center, three-part study of ION363 in up to 95 participants. Part 1 will

consist of participants who will be randomized in a 2:1 ratio to receive a multi-dose regimen

of ION363 or placebo for a period of 60 weeks, followed by Part 2, in which participants will

receive open-label ION363 for a period of 84 weeks. Participants may continue to receive

open-label ION363 in Part 3 for up to 3 additional years or until ION363 becomes commercially

available in the patient's country or until the Sponsor discontinues the ION363 development

program, whichever occurs earlier.

Ein-/Ausschlusskriterien

Inclusion Criteria for Part 1:

1. Participants must be ≥10 years of age at the time of informed consent and have signs

or symptoms consistent with an ALS disease (in the opinion of the Investigator).

2. Genetic mutation in FUS confirmed by a testing laboratory that is Clinical Laboratory

Improvement Amendments (CLIA) certified and European Conformity (CE)-marked, or

equivalent. Mutations must be reviewed and approved by a variant classification

committee.

3. Upright (sitting position) slow vital capacity (SVC) is ≥ 50% of predicted value (as

adjusted for sex, age, and height) OR if SVC is < 50% of predicted value, must be 10

to 30 years of age (inclusive) at the time of informed consent AND had ALS symptom

onset within 12 months before the time of informed consent.

4. Participants taking edaravone, riluzole, Relyvrio (sodium phenylbutyrate/taurursodiol

combination, called Albrioza in Canada), sodium phenylbutyrate, or

tauroursodeoxycholic acid (TUDCA, also known as taurursodiol or urosodiol) must be on

a stable dose for ≥ 28 days prior to Day 1, and willing to continue on that dose

throughout the duration of the study, unless the Investigator determines that it

should be discontinued for medical reasons, in which case it may not be restarted

during the study.

5. Stable concomitant medications and nutritional support for at least 1 month prior to

Study Day 1. Concomitant medications or nutritional support that have not been stable

for at least 1 month prior to Study Day 1 may be allowed in consultation with the

Sponsor Medical Monitor or designee.

6. Females must not be pregnant or lactating. Males and females must be willing to

following protocol-specified contraception requirements, or be surgically sterile, or

be post-menopausal (females).

7. Has an informant/caregiver who, in the Investigator's judgment, has frequent and

sufficient contact with the participant as to be able to provide accurate information

about the participant's cognitive and functional abilities throughout the study. In

addition, a patient who is < 18 years old must have a trial partner (parent,

caregiver, or other) who is reliable, competent, at least 18 years of age, and willing

to accompany the patient to all trial visits.

Inclusion Criteria for Part 2:

1. Completed, or rescued from, Part 1, or

2. Enrolled and received at least 1 dose of ION363 in the Investigator-initiated study

program

3. Patient meeting Criteria #1-2 is otherwise suitable for study participation, in the

opinion of the Investigator

Exclusion Criteria for Part 1:

1. Requiring permanent ventilation (> 22 hours of mechanical ventilation [invasive or

noninvasive] per day for > 21 consecutive days) and/or tracheostomy.

2. Any known genetic variant (other than those in the FUS gene) that is pathogenic or

likely to be pathogenic for the ALS-frontotemporal dementia (FTD) spectrum of disease.

3. Positive test result for:

1. Human immunodeficiency virus (HIV)

2. Hepatitis C (HCV), unless previously treated and has been serum/plasma HCV RNA

negative for at least 6 months after the end of treatment

3. Hepatitis B (HBV) by HBV surface antigen test, unless currently on

nucleotide/nucleoside analogue treatment

4. Clinically significant abnormalities in medical history (e.g., previous acute coronary

syndrome within 3 months before Screening, major surgery within 2 months before

Screening) or physical examination.

5. Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mm

Hg]).

6. Malignancy within 1 year before Screening, except for basal or squamous cell carcinoma

of the skin or carcinoma in situ of the cervix that has been successfully treated.

Participants with a history of other malignancies that have been treated with curative

intent and which have not recurred within 6 months may also be eligible per

Investigator judgement.

7. Obstructive hydrocephalus

8. Known significant brain or spinal disease that would interfere with the lumbar

puncture (LP) process, CSF circulation or safety assessment, including tumors or

abnormalities by magnetic resonance imaging (MRI) or computed tomography, subarachnoid

hemorrhage, suggestion of raised intracranial pressure on MRI or ophthalmic

examination, spinal stenosis or curvature, Chiari malformation, syringomyelia,

tethered spinal cord syndrome and connective tissue disorders such as Ehlers-Danlos

syndrome and Marfan syndrome.

9. Concurrent participation in any other interventional clinical study.

10. Previous or current treatment with an oligonucleotide (including small interfering RNA

[siRNA], tofersen). This exclusion criterion does not apply to COVID-19 vaccinations,

which are allowed.

11. Treatment with another investigational drug, biological agent, or device within 1

month before Screening, or 5 half-lives of investigational agent, whichever is longer.

12. History of gene therapy or cell transplantation or any other experimental brain

surgery.

13. Anticipated need, in the opinion of the Investigator, for administration of any

antiplatelet or anticoagulant medication that cannot be safely paused before and/or

after an LP procedure according to local or institutional guidelines and/or

Investigator determination after consultation with the appropriate treating physician.

Low-dose aspirin (≤ 100 mg/day, administered as monotherapy) is permitted and may be

continued through the LP procedure.

14. Have any other conditions, which, in the opinion of the Investigator would make the

participant unsuitable for inclusion or could interfere with the individual

participating in or completing the study, in the opinion of the Investigator.

Studien-Rationale

Primary outcome:

1. Change from Baseline (Day 1) through Study Day 505 in Part 1 in functional impairment (Time Frame - Baseline, Day 505 in Part 1):
Functional impairment to be measured by joint rank analysis of the combined assessment of: In-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score, time of rescue or discontinuation from Part 1 and entering Part 2 due to a deterioration in function, and ventilation assistance-free survival (VAFS). ALSFRS-R measures functional disease severity. The scale measures four functional domains, bulbar function, gross motor skills, fine motor skills, and respiratory function. The assessment will contain 12 questions scored from 0 (no function) to 4 (full function), with a total possible score of 48, which will indicate the highest level of function. ALSFRS-R will be a part of the combined assessment of joint rank analysis to assess efficacy in Part 1.

Secondary outcome:

1. Change from Baseline in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) Score to Day 505 in Part 1 (Time Frame - Baseline, Day 505 in Part 1):
The ALSSQOL-R is a disease-specific 50-item assessment that measures the quality of life. Each item will be rated by the participant on a scale of 0 to 10, with 0 being the least desirable situation and 10 being the most desirable.

2. Change from Baseline in the in-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) (Time Frame - Baseline, Day 505 in Part 1)

3. Survival and Ventilation Assistance-Free Survival (VAFS) (Time Frame - Up to Day 505 in Part 1)

4. Change from Baseline in In-clinic Slow Vital Capacity (SVC) to Day 505 in Part 1 (Time Frame - Baseline, Day 505 in Part 1)

5. Change from Baseline in Handheld Dynamometry (HHD) to Day 505 in Part 1 (Time Frame - Baseline, Day 505 in Part 1)

6. Change from Baseline in Neurofilament Light (NfL) Concentration in Cerebrospinal Fluid (CSF) to Day 505 (Time Frame - Baseline, Day 505 in Part 1)

7. Change from Baseline in FUS Concentration in Cerebrospinal Fluid (CSF) to Day 505 (Time Frame - Baseline, Day 505 in Part 1)

Studien-Arme

Experimental: ION363
ION363 will be administered by lumbar intrathecal (IT) bolus injection every 12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period in Part 1; every 12 weeks for 84 weeks in the open-label extension treatment period (Part 2), with an additional loading dose administered 4 weeks after the first dose. Patients may continue to receive open-label ION363 every 12 weeks in Part 3 for up to 3 additional years or until ION363 becomes commercially available in the patient's country or until the Sponsor discontinues the development program, whichever occurs earlier.
Placebo Comparator: Placebo
Placebo will be administered by lumbar IT bolus injection every12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period (Part 1).

Geprüfte Regime

ION363:
ION363 will be administered by IT bolus injection.
Placebo:
Placebo will be administered by IT bolus injection.

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!