An extension study to learn if Staccato Alprazolam is safe when treating long seizures in children ≥12 years of age and adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UCB Biopharma

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

26 Sep 2022 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

UCB Biopharma SRL

External identifiers

EU CT number

2023-508868-30-00

EudraCT number

2021-002637-42

WHO UTN

U1111-1299-3027

ClinicalTrials.gov

NCT05076617

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Therapy, Efficacy

Evaluation of the long-term safety and tolerability of Staccato alprazolam.

Secondary objectives 1

1. - Evaluation of the probability of success of repeated treatment with Staccato alprazolam (for seizures occurring within the first 12 months [up to a maximum of 10 treated seizures]) - Evaluation of the probability of success of repeated treatment with Staccato alprazolam with no recurrence of seizure(s) up to 2 hours (for seizures occurring within the first 12 months [up to a maximum of 10 treated seizures]) - Evaluation of the long-term pulmonary safety of Staccato alprazolam

Conditions and MedDRA coding

Treatment of stereotypical prolonged seizure

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003043-PIP01-21

Plan to share IPD

Yes

IPD plan description

Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of reidentifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Participant must be ≥12 years of age at the time of signing informed consent (or giving assent, where required) - Participant must have a study caregiver ≥18 years of age at the time of signing the informed consent; the study caregiver(s) must be able to recognize and observe the participant - Participants with an established diagnosis of focal or generalized epilepsy or combined focal and generalized epilepsy with a documented history of stereotypical episodes of prolonged seizures that includes at least 1 of the following: a) Generalized seizure episodes starting with a flurry of absence seizures or myoclonic seizures with a minimum total duration of 5 minutes b) Episodes of a focal seizure with a minimum duration of 3 minutes c) Episodes of a focal seizure or a flurry of myoclonic seizures for at least 90 seconds followed by a generalized/bilateral tonic-clonic seizure with a minimum total duration of 3 minutes - Prior to the Screening Visit, participant completed a study using Staccato alprazolam Additional inclusion criteria for treatment arms 2 to 5: Prior to the Screening Visit, the participant completed the Phase 3 efficacy study with Staccato alprazolam (EP0162) at a clinical site located in the EU, UK, and UA, and experienced an IMP-treated seizure during the Outpatient Treatment Period.

Exclusion criteria 1

1. - Participant has a current history of alcohol or drug use disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders 5, within the previous 1 year - Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) or comparable drugs (and/or an investigational device) as stated in this protocol or to albuterol (or similar bronchospasm rescue medication if needed to meet country- specific requirements) - Participant has a history of convulsive (generalized tonic-clonic) status epilepticus in the 8-weeks prior to the Screening Visit - Participant has a history or presence of known nonepileptic seizures which cannot be distinguished from qualifying epileptic seizures - Participant has a clinically significant known airway hypersensitivity (eg, bronchospasm to known allergens, such as pollen, animals, or food) and/or acute respiratory signs/symptoms (eg, shortness of breath, wheezing on lung auscultation) - Participant has a clinically significant chronic pulmonary disorder other than mild asthma (eg, chronic obstructive pulmonary disease, restrictive lung diseases [including idiopathic pulmonary fibrosis]) and/or recent history or presence of hemoptysis or pneumothorax - Participant has had a positive antigen test for SARS-CoV-2 and experienced moderate to severe signs/symptoms of respiratory distress necessitating hospitalization or outpatient treatment such as ambulatory oxygen, extensive treatment with inhaler medications, and/or oral medications for a duration of 4 weeks or more, unless full resolution occurred at least 6 months prior to Screening - Participant has experienced a severe upper respiratory tract infection within 4 weeks or severe bronchitis/pneumonia within 3 months before the Screening Visit - Participant has a history or presence of acute narrow-angle glaucoma - Participant has a condition for which oral alprazolam is contraindicated as per the regional labeling (eg, myasthenia gravis, severe respiratory insufficiency, and sleep apnea syndrome) - Participant has a history or presence of long QT syndrome, a family history of sudden death due to long QT syndrome, or unexplained syncope - Participant is taking any drug that is a strong CYP3A4 inhibitor, including azole antifungal agents (ketoconazole and itraconazole) and nefazodone - Participant is taking any opioids (eg, fentanyl, oxycodone, morphine) or sedative hypnotics on a chronic basis - Participant is taking nonselective beta blockers on a chronic basis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Frequency of treatment-emergent adverse events (TEAEs) 2. Frequency of TEAEs leading to withdrawal from study 3. Frequency of serious TEAEs

Secondary endpoints 1

1. 1. Treatment success after investigational medicinal product (IMP) administration for seizures occurring within the first 12 months 2. Treatment success after IMP administration with no recurrence after 2 hours for seizures occurring within first 12 months 3. Frequency of respiratory TEAEs

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UCB Biopharma

Sponsor organisation

UCB Biopharma

Address

Researchdreef 60

City

Anderlecht

Postcode

1070

Country

Belgium

Scientific contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Public contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Third parties 12

Locations

7 EU/EEA countries · 38 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 100 files

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

Application history

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