Medical Cannabis Treatment in Neurodegenerative Diseases (Neurobis)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2024-07-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministero della Salute - Direzione generale della ricerca e dell'innovazione in sanità.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

It will be determined whether the use of a balanced THC/CBD extract (cannabis extract Avextra 10/10 oral solution) is safe and suitable for contributing to a significant improvement in quality of life (QoL) in patients with a neurodegenerative disease (Alzheimer’s disease (AD), Parkinson’s disease (PD), or Amyotrophic Lateral Sclerosis (ALS).

To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving Quality of Life, assessed with the Short Form 36 Health Survey (SF-36), compared to placebo.

To assess for the total study population the safety and tolerability, incidence of treatment-emergent adverse events (TAEDs) and discontinuation rate of cannabis extract Avextra 10/10 compared to placebo.

Secondary objectives 5

1. To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving caregiver distress as assessed by a structured interview by an expert neuropsychologist using the Zarit Burden Interview (22-items) and the Caregiving Distress Scale. [By definition, a caregiver is a person available and living in the same household or interacting with the patient and available if necessary to assure administration of drug.]; also, the activities of daily living (ADL) and the Instrumental Activities of Daily Living scales (IADL) will be assessed on all patients.
2. To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving a patient-reported outcome measure evaluated through the Patient Global Impression of Change (PGIC) compared to placebo.
3. To demonstrate in the subpopulation of patients with Alzheimer’s disease (AD) superiority with regards to improvements on specific clinical disease marker functional disability using the standardized Mini Mental Status Examination (MMSE) to evaluate the cognitive functions and the Neuropsychiatric Inventory-agitation subscale for agitation in AD.
4. To demonstrate in the subpopulation of patients with Amyotrophic Lateral Sclerosis superiority with regards to improvements on specific clinical disease marker functional disability using the ALS functional rating scale - revised (ALSFRS-R) score for functional status in ALS.
5. To demonstrate in the subpopulation of patients with Parkinson’s disease superiority with regards to improvements on specific clinical disease marker functional disability using the unified Parkinson's disease rating scale (UPDRS) for monitoring the longitudinal course of PD.

Conditions and MedDRA coding

Patients suffering from neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease (AD) and Parkinson’s Disease (PD).

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. For all patients: ability to give written informed consent personally or, as an alternative, via a legally authorized representative. Patients >55years aged.
2. Alzheimer's Disease (AD): age diagnosis of AD based on the DSM-5 criteria for Major Neurocognitive Disorder due to AD; MMSE ≤ 24; presence of clinically significant agitation (Neuropsychiatric Inventory-agitation subscale ≥3). If treated with cognitive-enhancing medications (cholinesterase inhibitors (ChEIs) and/or memantine), the dosage must be stable for at least 3 months. If the ChEI and/or memantine have been discontinued, they may enroll after one month.
3. Amyotrophic Lateral Sclerosis (ALS): diagnosis of definite or probable according to El Escorial Criteria, documented progression of the disease in the last three months as measured by the ALSFRS-R scale (decrease of at least one point); age FVC ≥60% of predicted; treatment with riluzole 50 mg twice/day for at least one month before the screening visit.
4. Parkinson's Disease (PD): diagnosis of idiopathic Parkinson’s disease; modified Hoehn and Yahr stage 1 to 4; able to walk > 10 mt without aids or assistance; in treatment with L-Dopa with a stable dosage for at least 30 days.

Exclusion criteria 12

1. Current significant cardiovascular disease (e.g., uncontrolled hypertension, clinically significant ischemic heart disease, clinically significant arrhythmia or severe heart failure).
2. Chronic infections (HBV, HCV, HIV, tuberculosis)
3. Renal (serum creatinine > 2 mg/dl or creatinine clearance < 30 mL/min according to Cockcroft-Gault formula) and hepatic (ALT, AST, GGT, alkaline phosphatase > 2.5 ULN) failure.
4. Orthostatic hypotension.
5. Presence or history of other psychiatric disorders or neurological conditions (e.g., psychotic disorders, schizophrenia, epilepsy, attempted suicide, depression)
6. Alcohol and drug abuse.
7. Current use of cannabinoids or previous or current abuse or dependence on marijuana.
8. Contraindications to cannabidiol (history of hypersensitivity to any cannabinoid).
9. Change in psychotropic medications less than 1 month prior to study inclusion (e.g., concomitant antidepressants).
10. Clinically significant delusions and/or hallucinations.
11. Pregnancy and breastfeeding.
12. Inability to provide inform consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving Quality of Life, assessed with the Short Form 36 Health Survey (SF-36), compared to placebo.
2. To assess for the total study population the safety and tolerability, incidence of treatment-emergent adverse events (TAEDs) and discontinuation rate of cannabis extract Avextra 10/10 compared to placebo.

Secondary endpoints 5

1. To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving caregiver distress as assessed by a structured interview by an expert neuropsychologist using the Zarit Burden Interview (22-items) and the Caregiving Distress Scale.
2. To demonstrate for the total study population (all 3 neurodegenerative diseases) superiority with regards to improving a patient-reported outcome measure evaluated through the Patient Global Impression of Change (PGIC) compared to placebo.
3. To demonstrate in the subpopulation of patients with Alzheimer’s disease (AD) superiority with regards to improvements on specific clinical disease marker functional disability using the standardized Mini Mental Status Examination (MMSE) to evaluate the cognitive functions and the Neuropsychiatric Inventory-agitation subscale for agitation in AD.
4. To demonstrate in the subpopulation of patients with Amyotrophic Lateral Sclerosis superiority with regards to improvements on specific clinical disease marker functional disability using the ALS functional rating scale - revised (ALSFRS-R) score for functional status in ALS.
5. To demonstrate in the subpopulation of patients with Parkinson’s disease superiority with regards to improvements on specific clinical disease marker functional disability using the unified Parkinson's disease rating scale (UPDRS) for monitoring the longitudinal course of PD.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Sponsor organisation

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Address

Corso Giuseppe Mazzini 18

City

Novara

Postcode

28100

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Contact name

Letizia Mazzini

Public contact point

Organisation

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Contact name

Letizia Mazzini

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications