Recruiting
Phase 1/2
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
Condition(s) studied
Amyotrophic Lateral Sclerosis
Investigational drug(s) / intervention(s)
VTx-002Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone
VTx-002: An investigational gene therapy targeting a specific protein.
Preventative (Prophylactic) Medication - Corticosteroids: Methylprednisolone: To reduce the risk of reactions caused by the study treatment, steroid medicines will be given in advance.
Study summary
PIONEER-ALS is a Phase 1/2, multicenter, open-label, ascending dose, uncontrolled, first-in-human study that will evaluate the safety, tolerability and effects on clinical and biomarker endpoints of intracisternal administration of Vtx-002 in participants with Amyotrophic Lateral Sclerosis (ALS).
Two escalating dose (low dose and high dose) cohorts are planned. The duration of the study will be a maximum of 5 years and 5 weeks (265 weeks) for each participant. The screening period may last up to 5 weeks to complete screening procedures.
Eligibility
Key Inclusion Criteria:
1. Capable of, and willing to, provide written informed consent and comply with study procedures, including visits to the study site and visit requirements
2. Male or female ≥ 18 years of age
3. Has a diagnosis of ALS according to the El Escorial criteria (Brooks, et al., 2000) (probable, laboratory results supported; clinically probable, clinically definite)
4. Confirmed absence of ALS caused by FUS and SOD1 gene mutations confirmed by laboratory tests.
5. A maximum of 18 months since first appearance of weakness (e.g., limb weakness, dysarthria, dysphagia, shortness of breath)
6. Erect (seated) SVC % predicted ≥ 80% at Screening
7. Treatment Research Initiative to Cure ALS (TRICALS) risk score between -2 and -6 at Screening
8. Has a reliable caregiver/partner/legal representative willing and able to support the participant in participation in the study and to give informed consent on behalf of the participant in the case that disease progression prevents the participant of giving consent (local legal rules will apply).
9. Treatment with riluzole and/or edaravone is allowed if treatment was started and has remained at a stable dose for at least 2 weeks (riluzole) or one treatment cycle (edaravone) before the Screening visit
10. Women of childbearing potential (WOCBP) and male participants with female partners who are WOCBP must agree to use highly effective contraception during and after the study. WOCBP cannot be pregnant or breastfeeding
11. Women of nonchildbearing potential must be post-menopausal or surgically sterile (e.g. hysterectomy, bilateral tubal ligation, ovaries removed)
Key Exclusion Criteria:
1. Diagnosis of a significant CNS or peripheral nervous system disease other than ALS that may be a cause for the participant's ALS symptoms or may confound study objectives
2. Spinal, cervical, or brain MRI/MRA indicating clinically significant abnormality
3. Presence of tracheostomy and feeding tube at Screening
4. Contraindications to corticosteroid use (e.g. due to osteoporosis, uncontrolled blood pressure, diabetes or cholesterol).
5\. Significant concomitant disease or condition within 6 months of Screening that could pose an unacceptable safety risk to the participant or interfere with the participant's ability to comply with study procedures, e.g. heart disease, uncontrolled diabetes, liver disease, autoimmune diseases needing strong immune-suppressing drugs, cancer, etc or a current psychiatric diagnosis.
6\. Clinically significant abnormalities in laboratory test results at Screening for example poor liver or kidney function, abnormal clotting or infections such as Hepatitis or HIV
7\. Use of blood thinners (e.g., warfarin, heparin, and novel oral anticoagulants) and being unable to safely stop them before certain study procedures.
8\. Contraindications to imaging methods MRI, MRA, CT due to claustrophobia and/or intolerance to contrast agents.
9\. Contraindications to general anaesthesia (GA) or deep sedation
10 Positive test for illegal drugs (except prescribed medications or permitted medicinal/recreational marijuana if used responsibly)
11\. Generally frail or if the Investigator deems participation in the study would not be in the best interest of the participant or is likely to prohibit further participation during the study
Other protocol-defined inclusion/exclusion criteria may apply
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Primary outcome measure(s)
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — Over 5 years
Assessed by reviewing the nature, incidence, severity, relatedness, seriousness and outcome of treatment emergent adverse events.
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — Over 5 years
Assessed by reviewing laboratory values
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — Over 5 years
Assessed by reviewing Magnetic Resonance Imaging (MRI) findings.
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — over 5 years
Assessed by review of Treatment Induced Peripheral Neuropathy Assessment Scale (TNAS)
\*TNAS a brief participant-reported questionnaire used to measure the severity and progression of peripheral neuropathy. Each item is rated on a scale of 0 to 10, where 0 means no symptom and 10 means the symptom is as bad as it can possibly be.
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — Over 5 years
Assessed by reviewing cellular responses by analyzing blood samples.
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — Over 5 years
Assessed by reviewing scores of the Columbia Suicide Severity Rating Scale (C-SSRS)
\*C-SSRS is a widely used, evidence-based suicide risk assessment tool that helps identify whether someone is at risk for suicide and gauge the level of support needed. A low score is associated with a lower risk level in this brief questionnaire.
- The number of participants with treatment related adverse events (AEs) and Serious Adverse Events (SAEs) — At month 6 and month 12
Assessed by performing 4 formal interim analyses
1. 6 months after Gene Therapy Group 1 receive the single dose treatment
2. 6 months after Gene Therapy Group 2 receive the single dose treatment
3. 12 months after Gene Therapy Group 1 receive the single dose treatment
4. 12 months after Gene Therapy Group 2 receive the single dose treatment
Trial sites (11)
| Facility | City | Region | Status |
| St Joseph's Hospital and medical Center - Barrow Neurological Institute |
Phoenix |
Arizona |
Not Yet Recruiting |
| University of California San Diego Medical Center |
San Diego |
California |
Recruiting |
| Mayo Clinic in Florida |
Jacksonville |
Florida |
Recruiting |
| University of Miami School of Science |
Miami |
Florida |
Not Yet Recruiting |
| Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital |
Boston |
Massachusetts |
Recruiting |
| Herbert Irving Comprehensive Cancer Center |
New York |
New York |
Not Yet Recruiting |
| University of Pennsylvania |
Philadelphia |
Pennsylvania |
Recruiting |
| UZ Leuven |
Leuven |
Belgium |
Recruiting |
| UMC Utrecht |
Utrecht |
Netherlands |
Recruiting |
| Kings College Hospital |
London |
United Kingdom |
Not Yet Recruiting |
| Royal Hallamshire Hospital |
Sheffield |
United Kingdom |
Recruiting |
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