Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in Pediatric Patients With Type 2 Spinal Muscular Atrophy (SMA)
- Conditions
- Type 2 Spinal Muscular Atrophy
- Registration Number
- NCT05089656
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
To evaluate the efficacy, safety and tolerability of intrathecal (IT) OAV101 in treatment naive patients with Type 2 spinal muscular atrophy (SMA) who are ≥ 2 to \< 18 years of age over a 15 month trial duration.
- Detailed Description
This is a Phase III multi-center, single dose (1.2 x 1014 vector genomes), randomized, sham controlled, double-blind study that investigates the efficacy, safety and tolerability of OAV101B in treatment naive, sitting and never ambulatory SMA patients 2 to \<18 years of age.
Eligible participants received a single administration of OAV101B at the dose of 1.2 x 1014 vector genomes intrathecally or the sham procedure on Day 1 (Treatment Period 1), and were followed for a period of 52 weeks for Period 1. Period 2 is still ongoing.
The study consisted of a Screening and Baseline Period followed by two Treatment and Followup Periods. Participants were admitted to the hospital on Day 1 (or Day -1 as per local standards of care). After receiving OAV101B or the sham procedure on Day 1, participants underwent inpatient safety monitoring through Day 2 and optionally for Day 3.
After Period 1, eligible participants could continue to Period 2 subsequently entering Period 2 in a rolling seamless fashion as participants completed Follow-up Period 1. In Treatment Period 2, eligible participants who received a sham procedure on Study Day 1 of Treatment Period 1 were hospitalized to receive OAV101B on Week 52 + 1 day and participants who received OAV101B on Study Day 1 of Treatment Period 1 were hospitalized to receive a sham procedure on the Week 52 + 1 Day. The total duration of the study including both Period 1 and Period 2 is 64 weeks, currently Period 2 is ongoing. At the end of the study, all participants who received OAV101B are eligible to enroll in a long-term follow-up study to monitor long-term safety and efficacy.
This is the results of the primary analysis up to the end of Period 1 (Week 52).
The study is still ongoing.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 127
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Primary Outcome Measures
Name Time Method Change from baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 18 years age group Baseline up to 52 weeks The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
- Secondary Outcome Measures
Name Time Method Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 5 years age group Baseline up to 52 weeks The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Change from baseline in Revised Upper Limb Module (RULM) total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 18 years age group Baseline up to 52 weeks The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
Change from baseline in the RULM total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 5 years age group Baseline up to 52 weeks The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
Number of participants with treatment emergent Adverse Events and Serious Adverse Events Baseline up to 64 weeks An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
A Treatment Emergent Adverse Event (TEAE) is defined as an event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state.
The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the ≥ 2 to < 18 years age group Baseline up to 52 weeks The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the ≥ 2 to < 5 years age group Baseline up to 52 weeks The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
Number of participants with adverse events of special interest (AESIs) Baseline up to 64 weeks An AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows:
* Hepatotoxicity
* Thrombocytopenia
* Cardiac adverse events
* Dorsal Root Ganglia Toxicity
* Thrombotic microangiopathyNumber (and percentage) of patients with intracardiac thrombi Baseline up to 64 weeks Intracardiac thrombi is defined as the presence of thrombus on post-baseline echocardiograms
Number(and percentage) of patients with low cardiac function Baseline up to 64 weeks Low cardiac function is defined as left ventricular ejection fraction \<56% or left ventricular fractional shortening \<28% on post-baseline echocardigrams
Trial Locations
- Locations (16)
Connecticut Children's Medical Center
🇺🇸Farmington, Connecticut, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Clinic for Special Children
🇺🇸Strasburg, Pennsylvania, United States
St Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Children's Specialty Group/CHKD
🇺🇸Norfolk, Virginia, United States
Novartis Investigative Site
🇸🇬Singapore, Singapore
Peking University First Hospital
🇨🇳Beijing, China
Paediatric Neurology
🇩🇰Copenhagen, Denmark
Sir Ganga Ram Hospital
🇮🇳New Delhi, Delhi, India
P.D. Hinduja National Hospital & MRC
🇮🇳Mumbai, India
Scroll for more (6 remaining)Connecticut Children's Medical Center🇺🇸Farmington, Connecticut, United States