Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)

NCT04851873 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: COAV101A123062020-005995-37
• Study Type: interventional
• Target: 24
• Locations: 9 countries
• Sites: 13

Brief Summary

To evaluate the safety, tolerability and efficacy of intravenous administration of OAV101 (AVXS-101) in patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene weighing ≥ 8.5 kg and ≤ 21 kg, over a 12 month period.

Conditions

Spinal Muscular Atrophy

Keywords

Zolgensma; OAV101; AVXS 101; gene therapy; Muscle atrophy; SBMA; spinal and bulbar muscular atrophy; spinal muscular atrophy; bulbar muscular atrophy; muscle function; myopathy; muscle wasting; atrophied muscle; loss of muscle strength

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Weight Bracket

  An 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.

  Up to Month 12

• Number of Participants With Important Identified and Important Potential Risks (Adverse Events of Special Interest (AESI)) by Risk Name and Weight Bracket

  Important identified and important potential risks included the following AESIs: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Dorsal root ganglia toxicity and Thrombotic microangiopathy. These were assessed by the investigator.

  Up to Month 12

• Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Systolic and Diastolic Blood Pressure

  Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg). Systolic Blood Pressure-Low:\<=5th percentile of the age(Any Age), High:\>=90th percentile of the age, gender, and height group (\<18 yrs). Diastolic Blood Pressure-High:\>=90th percentile of the age, gender, and height group(\<18 yrs).

  12 months

• Change From Baseline in Vital Signs Measurements - Systolic Blood Pressure (mmHg)

  Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

• Change From Baseline in Vital Signs Measurements - Diastolic Blood Pressure (mmHg)

  Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

• Change From Baseline in Vital Signs Measurements - Respiratory Rate (Breaths/Min)

  Change from baseline in vital signs measurements - Respiratory Rate (breaths/min)

  Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

• Change From Baseline in Vital Signs Measurements - Pulse Rate (Beats/Min)

  Change from baseline in vital signs measurements - Pulse Rate (beats/min

  Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

• Summary of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values by Weight Bracket - Temperature

  Change from baseline in vital signs measurements - temperature (degrees Celsius) Temperature-Low:\<=35ºC(Any Age),High:\>=38.4ºC(\<18 yrs).

  12 months

• Change From Baseline in Vital Signs Measurements - Temperature (Degrees Celsius)

  Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

• Change From Baseline in Vital Signs Measurements - Oxygen Saturation Level

  Change from baseline in vital signs measurements - oxygen saturation level (%). Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated+saturated) in the blood and then multiplied by 100.

  Baseline, Days 2 and 3, Weeks 1, 2, 3, 4, 6, 8, 10, 13, 26, 39 and 52

Secondary Outcomes (3)

• Achievement of Development Motor Milestones According to the Modified and Combined WHO-MGRS and Bayley Scale of Infant and Toddler Development.

  Baseline, Week 26 and Week 52

• Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as Appropriate According to Participant Age

  Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52

• Change From Baseline in Revised Upper Limb Module (RULM), as Appropriate According to Participant Age.

  Baseline, Week 4, Week 13, Week 26, Week 39 and Week 52

Study Arms (1)

OAV101

EXPERIMENTAL

Participants received a single IV dose administration of OAV101

Genetic: OAV101

Interventions

OAV101 GENETIC

Gene Therapy - 1.1e14 vector genome (vg)/kg as a one-time IV infusion was administered over approximately 60 minutes.

OAV101

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic survival motor neuron 1 (SMN1) mutations (deletion or point mutations) and any copy of the survival motor neuron 2 (SMN2) gene.
• Weight ≥ 8.5 kg and ≤ 21 kg at the time of Screening Visit 2
• Naive to treatment or have discontinued an approved drug/therapy

You may not qualify if:

• Previous OAV101 use or previous use of any adeno-associated virus serotype 9 (AAV9) gene therapy
• BMI \< 3rd percentile
• Participant with history of aspiration pneumonia or signs of aspiration
• Elevated anti-AAV9 antibody
• History of gene therapy, hematopoietic transplantation, or solid organ transplantation
• Inability to take corticosteroids
• Concomitant use of immunosuppressive therapy
• Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation 9. Administration of vaccines 2 weeks prior to infusion of OAV101
• Awake hypoxemia or awake oxygen saturation level decrease
• Hepatic dysfunction
• Presence of a confirmed or suspected infection
• If previously treated with disease modifying therapy, specified washout times apply
• Documented any parental consanguinity.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Randwick, New South Wales, 2031, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

Location

Novartis Investigative Site

Garches, 92380, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Lisbon, 1600190, Portugal

Location

Novartis Investigative Site

Kaohsiung City, 80756, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

London, WC1N 3JH, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• McMillan HJ, Baranello G, Farrar MA, Zaidman CM, Moreno T, De Waele L, Jong YJ, Laugel V, Quijano-Roy S, Mercuri E, Chien YH, Straub V, Darras BT, Seibert J, Bernardo Escudero R, Alecu I, Freischlager F, Muntoni F; SMART Study Group. Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study. Neurology. 2025 Jan 28;104(2):e210268. doi: 10.1212/WNL.0000000000210268. Epub 2024 Dec 30.

  PMID: 39804575 DERIVED

Related Links

• If you have inquiries about possible participation in this clinical study, please go to this website, and select your region or country, to see if there is an investigator site near you.
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Muscular Diseases

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Musculoskeletal Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive a single administration of OAV101

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 21, 2021
• Study Start: September 8, 2021
• Primary Completion: June 13, 2023
• Study Completion: June 13, 2023
• Last Updated: October 9, 2024
• Results First Posted: January 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (2); FR (2); AU (1); CA (1); GB (2); PT (1); TW (2); IT (1); BE (1)