Estudio enmascarado, controlado con placebo, aleatorizado, piloto, de ApTOLL para el tratamiento de pacientes con ictus isquémico agudo a nivel pre-hospitalario, utilizando la escala RACE (Evaluación Rápida de la Oclusión Arterial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aptatargets S.L.

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)

2023-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AptaTargets S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The objective of this randomized pilot trial is to evaluate if the administration of ApTOLL 0.2 mg/kg intravenously (i.v.) at the pre-hospital level (in the ambulance) is feasible, safe and effective in order to guide future pivotal trials.

Conditions and MedDRA coding

Acute Ischemic Stroke (AIS)

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Suspected acute LVO (Large Vessel Occlusion) stroke patients identified by a RACE scale score >4 at the pre-hospital setting, identified in non-stroke ready centers or primary health centers, prior to the initial transfer to a CSC.
2. Patients located in Barcelona and Girona areas.
3. Estimated randomization time <6 hours from symptom onset, as evaluated at the pre-hospital setting. For wake-up strokes, onset time will be considered as the time of symptoms first discovered. (Treatment start is defined as study drug administration).
4. Non-significant pre-stroke functional disability (modified Rankin Scale 0 - 2), as evaluated at the pre-hospital setting.
5. Age ≥18 and ≤90 years old.
6. In case of women of childbearing potential (WOCBP), they should confirm menstrual period and a negative highly sensitive urine or serum pregnancy test to be included. Additionally, those WOCBP enrolled in the trial should adopt highly effective methods for birth control (i.e. intrauterine device, bilateral tubal occlusion, vasectomized partner, or sexual abstinence) for a period of 7 days after dose. If this statement can not be confirmed, WOCBP will be excluded. * a woman is considered of childbearing potential (WOCBP) i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy).

Exclusion criteria 9

1. Patients in a coma (NIHSS item of consciousness >1)
2. Patients with unstable clinical status who require emergent life support care
3. Serious, advanced, or terminal illness with anticipated life expectancy of less than 6 months.
4. Suspected LVO acute stroke patients identified at the Emergency Department of a stroke center or an intrahospital stroke.
5. Subject participating in a study involving an investigational drug or device that would impact this study.
6. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations. This excludes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.).
7. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas)
8. Evidence of active systemic infection
9. Pregnant or nursing (lactating) women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Enrolment of the desired sample size within the six-month enrolment window.
2. Time to enrol the planned participants
3. Proportion of eligible patients that are enrolled.
4. Time metrics related to pre-hospital workflows.
5. Proportion of patients who are not tracked after enrolling (lost-to-follow-up or withdrawal of consent).

Secondary endpoints 8

1. Rate of very poor outcome, as evaluated by a modified Rankin Scale (mRS) of 5 (very severe disability) or 6 (death) at 90 days
2. Mortality rate at 90 days.
3. All serious adverse events (SAEs) that occur within the first 90 days following randomization. The frequency of SAEs will be reported overall, as well as by specific organ involvement.
4. Early neurological worsening occurring after first hospital admission during the first seven days, as evaluated by an increase in the NIHSS score of 4 or more points, persisting for more than 24 hours, secondary to stroke progression, a symptomatic intracranial hemorrhage (Heidelberg criteria) the development of brain edema with midline shift associated with neurological worsening (malignant stroke), or hemorrhage expansion, as evaluated by the investigator.
5. Final infarct volume at 72±24 hours on MRI-FLAIR (Magnetic Resonance Imaging - FLuid-Attenuated Inversion Recovery).
6. NIHSS (National institute of Health Stroke Scale) score at 72 hours assessed by investigators during hospitalization.
7. Modified Rankin Scale at 90 days after randomization.
8. Proinflammatory markers in blood between study groups in the following populations according in all patients with stroke (intracranial hemorrhage [ICH] and ischemic stroke).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aptatargets S.L.

Sponsor organisation

Aptatargets S.L.

Address

Avenida Del Cardenal Herrera Oria 298

City

Madrid

Postcode

28035

Country

Spain

Scientific contact point

Organisation

Aptatargets S.L.

Contact name

Macarena Hernández

Public contact point

Organisation

Aptatargets S.L.

Contact name

María Eugenia Zarabozo

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Application history

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