TENECTEPLASE IN CENTRAL RETINAL ARTERY OCCLUSION STUDY (TenCRAOS): A Prospective, randomised-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomisation)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

30 Oct 2020 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-517606-29-00

EudraCT number

2018-002546-36

ClinicalTrials.gov

NCT04526951

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the effect of systemic tenecteplase within 4.5 hours of onset of CRAO.

Conditions and MedDRA coding

Central retinal artery occlusion

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Non-arteritic central retinal artery occlusion with ≥ 1.0 logMAR best-corrected visual acuity and symptoms lasting less than 4.5 hours. 2. Ability to administer the Investigator Medicinal Product (IMP) within 4.5 hours of symptom onset. 3. Age ≥18 years. 4. Informed written consent of the patient. 5. A woman of childbearing potential (WOCBP) must confirm that in her opinion, she cannot be pregnant, OR if there is a possibility that she is pregnant, a negative pregnancy test must be confirmed before any IMP is given.

Exclusion criteria 1

1. 1. Non-arteritic central retinal artery occlusion with ≥ 1.0 logMAR best-corrected visual acuity and symptoms lasting less than 4.5 hours. 2. Ability to administer the Investigator Medicinal Product (IMP) within 4.5 hours of symptom onset. 3. Age ≥18 years. 4. Informed written consent of the patient. 5. A woman of childbearing potential (WOCBP) must confirm that in her opinion, she cannot be pregnant, OR if there is a possibility that she is pregnant, a negative pregnancy test must be confirmed before any IMP is given. 1. No other active intervention targeting CRAO. 2. Branch retinal artery occlusion, cilioretinal artery supplying the macula, combined arterial-venous occlusion, proliferative diabetic retinopathy, elevated intraocular pressure (> 30 mmHg) or clinical suspicion of ophthalmic artery occlusion (e.g. choroidal nonperfusion, absence of cherry red spot, no light perception). 3. Systemic diseases; severe general diseases, systemic arterial hypertension (blood pressure >185/110 mmHg (2)), despite medical therapy, or clinical suspicion of acute systemic inflammation. 4. Presence of intracranial haemorrhage on brain MRI/CT. 5. Medical history: heart attack within the last 6 weeks, intracerebral bleeding or neurosurgical operation within the last 4 weeks, therapy with anticoagulation, allergic reaction to contrast agent, hemorrhagic diathesis, aneurysms, inflammatory vascular diseases (eg, giant cell arteritis, granulomatosis with polyangitis), endocarditis, or gastric ulcer. 6. No willingness and ability of the patient to participate in all follow-up examinations. 7. Pregnancy (if suspicion of pregnancy s-hCG or u-hCG must be negative). 8. Allergy or intolerance to any ingredients of IMP (including placebo) or gentamicin or acetylsalicylic acid. 9. Other conditions / circumstances likely to lead to poor treatment adherence (eg, history of poor compliance, alcohol or drug dependency, no fixed abode). 10. Significant bleeding disorder either at present or within the past 6 months. 11. Effective oral anticoagulant treatment, eg, warfarin sodium (INR >1.3). 12. Effective anticoagulant treatment with heparin or low molecular weight heparin the last 48 hours. 13. Any history of central nervous system damage (ie, neoplasm, aneurysm, intracranial or spinal surgery). 14. Known hemorrhagic diathesis. 15. Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with acute myocardial infarction). 16. Recent non-compressible vessel puncture within 2 weeks. 17. Recent trauma to the head or cranium. 18. Prolonged cardiopulmonary resuscitation (>2 minutes) within the past 2 weeks. 19. Acute pericarditis and/or subacute bacterial endocarditis. 20. Acute pancreatitis. 21. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis. 22. Active peptic ulceration. 23. Arterial aneurysm and known arterial/venous malformation. 24. Neoplasm with increased bleeding risk. 25. Any known history of hemorrhagic stroke or stroke of unknown origin. 26. Known history of ischemic stroke or transient ischemic attack in the preceding 3 months. 27. Dementia.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint: Proportion of patients with ≤ 0.7 logMAR best-corrected visual acuity in the affected eye at 30 (±5) days after treatment, representing an improvement in best-corrected visual acuity of at least 0.3 logMAR (intention-to-treat (ITT) analysis).

Investigational products

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

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

CI

Public contact point

Organisation

Oslo University Hospital HF

Contact name

CI

Third parties 2

Locations

6 EU/EEA countries · 18 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 17 files

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

Application history

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