A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (Rainbowfish)

Roche

Status and phase

Active, not recruiting

Phase 2

Conditions

Muscular Atrophy, Spinal

Treatments

Drug: Risdiplam

Study type

Interventional

Funder types

Industry

Identifiers

NCT03779334

2023-506009-20-00 (Registry Identifier)

2018-002087-12 (EudraCT Number)

BN40703

Details and patient eligibility

About

A global study of oral risdiplam in pre-symptomatic participants with spinal muscular atrophy (SMA).

Full description

The study is an open-label, single-arm, multicenter clinical study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in infants aged from birth to 6 weeks who have been genetically diagnosed with SMA but are not yet presenting with symptoms. There will be a screening, treatment, open-label extension (OLE) and a follow-up. All participants will receive risdiplam orally once daily for 2 years followed by an OLE phase of at least 3 years and a follow-up (if applicable), for a total treatment duration of at least 5 years for each participant enrolled.

Enrollment

26 patients

Sex

All

Ages

1 day to 6 weeks old

Volunteers

No Healthy Volunteers

Inclusion criteria

Males and females aged from birth (1 day) to 6 weeks (42 days) of age at the time of first dose (Day 1); a minimum age of 7 days at first dose is required for the first infant to be enrolled
Gestational age of 37-42 weeks for singleton births; gestational age of 34-42 weeks for twins
Body weight >= 3rd percentile for age, using appropriate country-specific guidelines
Genetic diagnosis of 5q-autosomal recessive SMA, including confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the SMN1 gene
Absence of clinical signs or symptoms at screening (Day -42 to Day -2) or at baseline (Day -1) that are, in the opinion of the investigator, strongly suggestive of SMA
Receiving adequate nutrition and hydration at the time of screening, in the opinion of the investigator
Adequately recovered from any acute illness at baseline and considered well enough to participate in the study, in the opinion of the investigator
Able and expected to be able to safely travel to the study site for the entire duration of the study and in accordance to the frequency of required study visits, in the opinion of the investigator
Able to complete all study procedures, measurements, and visits, and the parent (or caregiver), in the opinion of the investigator, has adequately supportive psychosocial circumstances
Parent (or caregiver) is willing to consider nasogastric, naso-jejunal, or gastrostomy tube placement during the study to maintain safe hydration, nutrition, and treatment delivery, if recommended by the investigator
Parent (or caregiver) is willing to consider the use of non-invasive ventilation during the study, if recommended by the investigator

Exclusion criteria

Concomitant or previous participation in any investigational drug or device study at any time
Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide, SMN2-splicing modifier, or gene therapy either in a clinical study or as part of medical care
Presence of significant concurrent syndromes or diseases
In the opinion of the investigator, inadequate venous or capillary blood access for the study procedures
Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation
Awake hypoxemia (SaO2 < 95%) with or without ventilator support
Multiple or fixed contractures and/or hip subluxation or dislocation at birth
Systolic blood pressure or diastolic blood pressure or heart rate considered to be clinically significant by the investigator
Presence of clinically relevant ECG abnormalities before study drug administration; corrected QT interval using Bazett's method > 460 ms; personal or family history (first degree relatives) of congenital long QT syndrome indicating a safety risk for patients as determined by the investigator. First-degree atrioventricular block or isolated right bundle branch block are allowed
The infant (and the mother, if breastfeeding the infant) taking any inhibitor of CYP3A4 taken within 2 weeks, any inducer of CYP3A4 taken within 4 weeks, any OCT 2 and MATE substrates within 2 weeks and known FMO1 or FMO3 inhibitors or substrates
Clinically significant abnormalities in laboratory test results
Ascertained or presumptive hypersensitivity to risdiplam or to the constituents of its formulation
Treatment with oral salbutamol or another beta-2 adrenergic agonist taken orally for SMA is not allowed. Use of inhaled beta-2 adrenergic agonists is allowed
Infants exposed to drugs with known retinal toxicity given to mothers during pregnancy (and lactation) should not be enrolled. Anticipated need for drugs known to cause retinal toxicity during the study.
Diagnosis of ophthalmic diseases