An outpatient study to learn if Staccato Alprazolam is safe and effective 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

21 Jul 2022 → ongoing

Decision date (initial)

2024-09-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

UCB Biopharma SRL

External identifiers

EU CT number

2024-510950-29-00

EudraCT number

2021-002686-18

WHO UTN

U1111-1303-2588

ClinicalTrials.gov

NCT05077904

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others, Therapy, Efficacy

Comparison of the success of a single administration of Staccato alprazolam compared with placebo both in rapidly terminating a seizure episode within 90 seconds and with no recurrence of seizure(s) up to 2 hours after investigational medicinal product (IMP) administration.

Secondary objectives 1

1. - Comparison of the success of a single administration of Staccato alprazolam compared with placebo both in rapidly terminating a seizure episode within 90 seconds and with no recurrence of seizure(s) up to 4 hours after IMP administration - Comparison of the success of a single administration of Staccato alprazolam compared with placebo both in rapidly terminating a seizure episode within 90 seconds and with no recurrence of seizure(s) up to 6 hours after IMP administration - Comparison of the time from IMP administration to cessation of the treated seizure between Staccato alprazolam and placebo - Evaluate the pulmonary safety of a single dose of Staccato alprazolam compared with placebo - Comparison of the occurrence of subsequent seizure(s) up to 2 hours after IMP administration between Staccato alprazolam and placebo

Conditions and MedDRA coding

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 Baseline/Randomization Visit - Participant must have a study caregiver ≥18 years of age at the Screening Visit; the study caregiver(s) must be a relative, partner, friend, or legally authorized representative (LAR) of the participant, or a person who provides daily care to the participant and has a significant personal relationship with the participant; the study caregiver(s) must be able to recognize and observe the participant's seizures - 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 has experienced ≥4 stereotypical episodes of prolonged seizures in the past 6 months, and the last 2 stereotypical episodes of prolonged seizures must have occurred within the 3 months prior to the Screening Visit - Participant has had a documented brain computerized tomography or magnetic resonance imaging review, performed after diagnosis of epilepsy and within the 5 years prior to the Screening Visit, that confirms the absence of a progressive neurological disorder - Participant is receiving a regimen of antiseizure medications (ASMs) that has been stable (ie, no addition or removal of ASM[s]; dose adjustments are permitted to ASM[s]; dose adjustments are not permitted for benzodiazepines) for 30 days prior to the Screening Visit - Male and female participants: a) A male participant must agree to use contraception during the Outpatient Treatment Period and for at least 7 days after investigational medicinal product (IMP) administration and refrain from donating sperm during this period b) A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the Outpatient Treatment Period and for at least 30 days after IMP administration - Participant is capable of giving signed informed consent (or giving assent, where required), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF), the protocol, and the individualized participant management plan (iPMP). The informed consent form (ICF), or a specific assent form, where required, will be signed and dated by minors - The participant's study caregiver(s) must be capable of giving signed informed consent), which includes compliance with the requirements and restrictions listed in the ICF, the protocol, and the individualized participant management plan (iPMP)

Exclusion criteria 1

1. - A history of alcohol or drug use disorder - A known hypersensitivity to any components of the IMP or comparable drugs (and/or an investigational device) or to albuterol (or similar bronchospasm rescue medication) - A diagnosis of atrial fibrillation or mitral stenosis - A history of convulsive status epilepticus in the 8 weeks prior to Screening - Has nonepileptic seizures indistinguishable from qualifying epileptic seizures - Has airway hypersensitivity and/or acute respiratory signs/symptoms - Has chronic pulmonary disorder other than mild asthma and/or recent history or presence of hemoptysis or pneumothorax - Tested positive for SARS-CoV-2 and experienced moderate to severe signs/symptoms of respiratory distress needing hospitalization or outpatient treatment such as ambulatory oxygen, treatment with inhaler medications, and/or oral medications for 4 weeks or more, unless resolved at least 6 months prior to Screening - Has experienced an upper respiratory tract infection within 4 weeks or bronchitis/pneumonia within 3 months of Screening - A history or presence of acute narrow-angle glaucoma - Has a condition where oral alprazolam is contraindicated - A history or presence of long QT syndrome, a family history of sudden death due to long QT syndrome, or unexplained syncope - Is taking any drug that is a strong CYP3A4 inhibitor, including azole antifungal agents (ketoconazole and itraconazole) and nefazodone - Is taking any opioids or sedative hypnotics on a chronic basis - Is taking nonselective beta blockers on a chronic basis - Is taking pharmacotherapy for an active psychiatric disorder and changes in regimen are anticipated during the study - Has laboratory abnormality that may increase risk associated with participation or may interfere with the interpretation of study results - Has an oxygen saturation <95 % (or less than normal in regions of altitude >2500 meters) for greater than 30 seconds during Screening. In case of an out-of-range result, 1 repeat will be allowed, if out of range again, the participant will be excluded - Has >2.0x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >1.0xULN total bilirubin (≥ 1.5xULN total bilirubin if known Gilbert's syndrome or >2.0xULN total bilirubin for liver impairment) -Has current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis - Has a QT interval corrected for heart rate (QTc) >450 msec (males), QTc interval >470 msec (females), or QTc interval >480 msec (participants with bundle branch block), PR interval ≥220msec, or any other electrocardiogram (ECG) abnormality i) The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), either machine-read or manually over-read - A positive urine screen for drugs of abuse at Screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment success for the treated seizure with no recurrence after 2 hours

Secondary endpoints 6

1. Treatment success for treated seizure with no recurrence after 4 hours
2. Treatment success for treated seizure with no recurrence after 6 hours
3. Time from IMP administration to cessation of the treated seizure
4. Frequency of respiratory treatment emergent adverse events (TEAEs)
5. Number of subsequent seizure(s) up to 2 hours after IMP administration
6. Time to first subsequent seizure up to 2 hours after IMP administration

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 11

Locations

8 EU/EEA countries · 43 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 192 files

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

Application history

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