FOCUS-C9: Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)

Sponsor

Wave Life Sciences Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04931862

Collaborator

(none)

Enrollment

Locations

Arms

19.2

Anticipated Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of intrathecal (IT) WVE-004 in adult patients with C9orf72-associated ALS or FTD. To participate in the study, patients must have a documented mutation (GGGGCC [G4C2] repeat expansion) in the first intronic region of the C9orf72 gene and be diagnosed with ALS or FTD.

Condition or Disease	Intervention/Treatment	Phase
ALS FTD	Drug: WVE-004 Drug: Placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-004 Administered Intrathecally to Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)

Actual Study Start Date :

Jun 28, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: WVE-004 (Dose A) or placebo	Drug: WVE-004 WVE-004 is a stereopure antisense oligonucleotide (ASO) Drug: Placebo Artificial cerebrospinal fluid (aCSF)
Experimental: WVE-004 (Dose B) or placebo	Drug: WVE-004 WVE-004 is a stereopure antisense oligonucleotide (ASO) Drug: Placebo Artificial cerebrospinal fluid (aCSF)
Experimental: WVE-004 (Dose C) or placebo	Drug: WVE-004 WVE-004 is a stereopure antisense oligonucleotide (ASO) Drug: Placebo Artificial cerebrospinal fluid (aCSF)
Experimental: WVE-004 (Dose D) or placebo	Drug: WVE-004 WVE-004 is a stereopure antisense oligonucleotide (ASO) Drug: Placebo Artificial cerebrospinal fluid (aCSF)

Outcome Measures

Primary Outcome Measures

Safety: Proportion of patients with adverse events (AEs) [Period 1 Day 1 to Period 2 Week 24 (end of study)]

Secondary Outcome Measures

Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF) [Period 1 Day 1 to Period 2 Week 24 (end of study)]
Pharmacodynamic: Change from baseline in concentration of poly-GP levels in the CSF [Period 1 Day 1 to Period 2 Week 24 (end of study)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ALS-specific: Diagnosis of ALS based on clinical manifestations.
ALS-specific: Clinically diagnosed possible, laboratory supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology revised El Escorial criteria.
ALS-specific: Patients receiving riluzole have been on a stable dose for a minimum of 30 days.
ALS-specific: Patients on edaravone have received a minimum of 1 cycle (28 days).
ALS-specific: Patients discontinuing riluzole or edaravone had the last dose administered ≥1 month prior to Screening.
FTD-specific: Must have Global Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR® plus NACC FTLD) score of 0.5 or 1.
FTD-specific: Able to undergo periodic magnetic resonance imaging (MRI) of the brain. Participants with mixed phenotype (ALS and FTD) need not undergo MRI if their ALS symptoms prevent it.
Mixed-phenotype: Patients who are mixed phenotype (ALS and FTD) must meet both the ALS-specific and FTD-specific criteria.

Exclusion Criteria:

Clinically significant medical finding on the physical examination other than C9orf72-associated ALS or FTD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the trial procedures
Received any other investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Received an investigational oligonucleotide, within the past 6 months or 5 half-lives of the drug, whichever is longer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Macquarie University	North Ryde	New South Wales	Australia	2109
2	The Wesley Hospital	Brisbane	Queensland	Australia	QLD 4066
3	Perron Institute	Nedlands	Western Australia	Australia	6009
4	UZ Leuven	Leuven		Belgium	3000
5	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
6	McGill University Health Center - Research Institute	Montréal	Quebec	Canada
7	St James Hospital - Ireland	Dublin		Ireland	D08 NHY1
8	Erasmus University MC	Rotterdam		Netherlands	3015
9	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands
10	Auckland City Hospital	Auckland		New Zealand	1023
11	New Zealand Brain Research Institute	Christchurch		New Zealand	8011
12	University College London Hospital	London		United Kingdom	WC1N 3BG
13	King's College Hospital	London		United Kingdom	WC2R 2LS
14	University of Oxford - Nuffield Department of Clinical Neurosciences	Oxford		United Kingdom	OX3 7LF
15	University of Sheffield	Sheffield		United Kingdom	S10 2TN