Treating severe brain-injured patients with apomorphine

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universite De Liege, CHU De Liege

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Sep 2018 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Britannia Pharmaceuticals Limited

External identifiers

EU CT number

2023-504631-40-01

EudraCT number

2018-003144-23

ClinicalTrials.gov

NCT05213169

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

This clinical trial aims to clarify the prevalence of responders and the efficacy of apomorphine hydrochloride subcutaneous infusions for the treatment of patients with disorders of consciousness.

Secondary objectives 1

1. This study aims to also better characterize the phenotype of potential good candidates to apomorphine treatment and identify a set of biomarkers that correlate with responsiveness (or non-responsiveness) to the therapy, as well as help underpin the neural networks underlying the modulating action of apomorphine on consciousness.

Conditions and MedDRA coding

Disorder of Consciousness, severe brain injury

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 18-70 years old, cinically stable, diagnosed as in an unresponsive wakefulness syndrome or minimally conscious state according to the international criteria and based on at least 2 consistent CRS-R in the last 14 days (one CRS-R in the last 7 days), more than 4 weeks post-insult, informed consent from patient or legal representative of the patient.

Exclusion criteria 1

1. Use of dopamine agonists or antagonists (e.g. amantadine, bromocriptine, l-dopa, pramipexole, ropinirole, amphetamine, bupropion, methylphenidate / risperidone, haloperidol, chlorpromazine, flupentixol, clozapine, olanzapine, quetiapine) in the last 2 weeks or 4 half-lives of the drug; use of neurological medications other than anti-epileptic or anti-spasticity drugs in the last 2 weeks or 4 half-lives of the drug; use of drugs with known significant prolongation of the QT interval (e.g. class 1 antiarrythmics, sotalol, macrolides, quinolones, antipsychotic drugs, tricyclic antidepressants, methadone, chloroquine, quinine) in the last 2 weeks or 4 half-lives of the drug; corrected QT interval over 480ms (calculated using Bazett’s formula on a standard 12-lead ECG recorded in the last 14 days) or other risk factors for arrhythmia (congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance); history of previous neurological functional impairment other than related to their acquired brain injury; contraindication to MRI, EEG, or PET (e.g., electronic implanted devices, active epilepsy, external ventricular drain); use of nitrates or other vasodilators, central nervous system acting agents such as barbiturates, morphine and related drugs (relative exclusion criterion).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change of diagnosis from baseline in Coma Recovery Scale - Revised (CRS-R)

Secondary endpoints 9

1. Change of total score in Nociception Coma Scale - Revised (NCS-R)
2. Changes in EEG spectral power within fixed bands or dynamic connectivity using median spectral connectivity and graph-theoretic topology metrics
3. Changes in the probabilty of consciousness using a multivariate EEG classifier based on a machine-learning approach using 120 EEG markers
4. Changes in quantification of PET signal using standardized uptake values of fluorodeoxyglucose
5. Changes in MRI functional connectivity using a seed-voxel approach, between regions of interest (here: striatum, globus pallidus interna, thalamus and prefrontal cortex) and the time course from all other brain voxels
6. Change in circadian rhythmicity using actimetry and body temperature variations
7. Change in the architecture of sleep cycles using night EEG
8. Change of score in Glasgow Outcome Scale - Extended (GOS-E)
9. Change in diagnosis in Phone-adapted CRS-R

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universite De Liege

Sponsor organisation

Universite De Liege

Address

Avenue De L'hopital 3

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Universite De Liege

Contact name

Olivia Gosseries

Public contact point

Organisation

Universite De Liege

Contact name

Olivia Gosseries

CHU De Liege

Sponsor organisation

CHU De Liege

Address

Avenue De L'hopital 1

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

CHU De Liege

Contact name

Vincent Bonhomme

Public contact point

Organisation

CHU De Liege

Contact name

Vincent Bonhomme

Sponsor responsibilities

Article 77 compliance

Universite De Liege

Contact point sponsor

Universite De Liege

Article 77 implementation

Universite De Liege

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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