SonoCloud-4 (SC4) device: Implantation of SC4 device and 9 Blood Brain Barrier opening sessions by ultrasound without any associated drug
Study summary
This is proof-of-concept, single-arm, single-center study to assess the safety and explore the efficacy of repeated US transient disruptions of the blood-brain barrier (BBB) in Amyotrophic Lateral Sclerosis (ALS).
Phase 1:
The primary objective is to assess the safety of ultrasound induced BBB opening in the upper motor neuron area and adjacent supplementary motor area in adult patients with ALS, as assessed by adverse events frequency and severity during study (incidence of AE summarized by system organ class and/or preferred term and severity) based on the Common Terminology Criteria for Adverse Events, version 5.0 A run-in period of 12 weeks between inclusion and baseline will take place for each patient in order to evaluate precisely disease progression rate, disease severity and to collect concomitant medication. After this run-in period, the patient will be implanted with the SC4 device (baseline visit). The first sonication session will be performed two weeks after implantation. A total of 9 sonications, with no concomitant drug administration, will be performed over a period of 24 weeks.
Phase 2a:
Based on the safety outcome of the Phase 1, an expansion cohort will open to assess the first signal of efficacy of the US transient disruptions of the BBB in ALS. The primary objective will be to assess the first signal of efficacy of the procedure on disease progression over 26 weeks evaluated by the change from baseline to week 26 of neurofilament light (NfL) levels in blood.The Phase 2a will continuously include 11 additional patients. Patients will be treated according to the same schedule as in phase 1
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
1. Age 18-80 years,
2. Able and willing to give signed and informed consent
3. Confirmed diagnosis of ALS using the Gold Coast criteria with involvement of both upper and lower motor neurons in at least one body region, i.e. patients classified as "definite", "probable", "probable laboratory supported" or "possible" ALS using the El Escorial categories (patients with only lower motor neuron involvement will not be included)
4. Disease duration \<= 36 months,
5. Mild functional impairment (ALSFRS-R ≥30),
6. Change in ALSFRS-R score between 0.35 points and 1.1 points per month (both inclusive) in the period from onset of first symptoms to the Screening visit,
7. Slow Vital capacity \>= 70% of normal,
8. If taking riluzole, patient on stable dose for over 30 days prior to study entry,
9. Able and willing to follow trial procedures including site travels and visit requirements
Exclusion Criteria:
1. Patients with an uncontrolled intercurrent illness or any pre-existing comorbidities that in the Investigator's opinion may prevent the implantation of the device or may impair the ability of the patient to receive treatment with SonoCloud or may be cofounding for evaluation of the clinical trial
2. Cardiac pacemaker (contraindication to MRI)
3. Allergy to any drug used in the study (Gadolinium, Xylocain, Cloxacilline, EMLA, echographic contrast agent microbubbles: SonoVue®)
4. Severe or instable chronic or acute disease or any life-threatening condition
5. Other significant neurological or psychiatric disease in addition to ALS, including history of uncontrolled seizures
6. Treatment with edaravone, tofersen or with another investigational drug or biological agent within 1 month or 5 half-lives of study agent, whichever is longer, before screening
7. Invasive or non-invasive mechanical ventilation use
8. Gastrostomy or nasogastric tube use
9. Known right-to-left shunts,
10. Known severe pulmonary hypertension (pulmonary artery pressure \>90 mmHg), uncontrolled systemic hypertension
11. Known respiratory distress syndrome
12. Women of child-bearing potential or sexually active man, without contraception
13. Pregnant or breast-feeding woman
14. History or positive test result at screening for HIV, current hepatitis C infection (defined as positive HCV antibody and detectable HCV RNA) or current hepatitis B infection (defined as positive for HBsAg and/or total anti-HBc). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study. Participants with immunity to hepatitis B from previous natural infection (defined as negative HbsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HbsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
15. Patient not affiliated or beneficiary of a social security category
Primary outcome measure(s)
Phase 1 : Adverse events frequency and severity during study to assess the safety of ultrasound induced BBB opening in the upper motor neuron area and adjacent supplementary motor area — from inclusion up to 50 weeks incidence of AE summarized by system organ class and/or preferred term and severity based on the Common Terminology Criteria for Adverse Events, version 5.0
Phase 2a : Neurofilament light (NfL) levels in blood to assess the first signal of efficacy of the procedure on disease progression — from baseline to 26 weeks Change from baseline to week 26 of neurofilament light (NfL) levels in blood
Trial sites (1)
Facility
City
Region
Status
Hôpital Pitié-Salpêtrière
Paris
France
Recruiting
More Assistance Publique - Hôpitaux de Paris trials in France
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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