Phase 1b/2a clinical trial to determine the safety, tolerability and efficacy of TZ-161 in Spinal Cord Injury

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

9 Jul 2025 → ongoing

Decision date (initial)

2024-06-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

- Evaluate the safety and tolerability of IMP plus SOC versus SOC alone in adult subjects with early acute SCI.

- Compare the efficacy of IMP plus SOC versus SOC alone in the treatment of early acute SCI regarding ASIA AIS motor and sensory scores.

Secondary objectives 2

1. Compare IMP plus SOC versus SOC alone in the treatment of acute SCI concerning spasticity and pain evaluated respectively by: - MAS ; - BPI
2. Compare IMP plus SOC versus SOC alone in the treatment of acute SCI regarding: - ICU length of stay; - Hospital length of stay.

Conditions and MedDRA coding

Early acute spinal cord injury

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subjects aged 18-65 years old.
2. Subjects with clinical diagnosis of acute SCI that comply with the following: a. Injury located on the thoracic region (T1 to T12). b. With clinical suspicion of a single traumatic (contusion) lesion. c. AIS grade of grade B, C or D with a motor score less than or equal to 3 in at least one key muscle of a lower limb. d. Ability to perform injury-to-drug administration ≤ 48 hours after SCI.
3. Subjects willing and able to provide an informed consent.
4. Subjects willing and able to complete the study and comply with instructions.

Exclusion criteria 16

1. Clinical or imaging suspicion of multi-lesion or extra-thoracic contusions on diagnostic CT scan and on MRI at 72H.
2. Subjects in coma or with significant cognitive impairment in the opinion of the investigator.
3. Subjects presenting mechanical ventilation dependence.
4. Subjects with past medical history of any - structural - neurological disorder of the central or peripheral nervous system, including past spinal cord injury. Furthermore, subjects with spine/bone-related medical history (prior to SCI) that in the opinion of the investigator are not yet resolved or previous lesions that are located in the same area of the study SCI should also be excluded.
5. Subjects with dysphagia or inability to swallow tablets.
6. Women who are breastfeeding or who are pregnant. Pregnancy to be excluded during screening by presence of a negative blood pregnancy test.
7. Subjects with active malignancy, or malignancy in the last 5 years taking prohibited medication.
8. Subjects that have recently used Eletriptan HBr (within the last 48h).
9. Subjects presenting clinically significant ECG abnormalities (Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders) at screening.
10. Subjects presenting any contraindications, special warnings, and precautions regarding IMP administration, as per described in the SmPC of Eletriptan HBr: a. Ischemic CAD, such as angina pectoris, history of myocardial infarction, and documented silent ischemia, or coronary artery vasospasm, including Prinzmetal’s angina. b. Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. c. History of stroke, TIA, or history or current evidence of hemiplegic or basilar migraine because these patients are at a higher risk of stroke. d. Peripheral vascular disease. e. Ischemic bowel disease. f. Uncontrolled hypertension. g. Recent use (i.e. 48 hours) of serotonin receptor agonists h. Coadministration with SSRIs, SNRIs, TCAs, and MAO due to risk of serotonin syndrome. i. Recent use (i.e., within 48 hours) of drugs containing ergotamine or ergot-like substances (such as dihydroergotamine or methysergide) j. Hypersensitivity to IMP and its excipients (angioedema and anaphylaxis seen).
11. The following medications and/or substances are not allowed due to potential interaction with Eletriptan HBr or inhibition of the CYP3A4 system (recent use, i.e., within at least 72 hours): a. Cimetidine; ketoconazole; itraconazole; fluconazole, erythromycin; clarithromycin, troleandomycin, verapamil, and MAO inhibitors [such as isocarboxazid (Marplan), phenelzine sulfate (Nardil), tranylcypromine (Parmate), selegiline (Emsam)], pioglitazone, and valerian. b. Antiretrovirals - such as ritonavir, indinavir, nelfinavir, efavirenz and nevirapine. c. Other prohibited concomitant medications include haloperidol, trazodone, triazolam, nefazodone, diltiazem, carbamazepine, phenytoin, oxcarbazepine, and phenobarbital. d. St. John's Wort (Hypericum perforatum).
12. Subjects with known liver disease (except for Child Pugh A) or severe hepatic impairment.
13. Subjects with known renal disease or severe renal impairment – exclude if eGFR below 50 ml/min.
14. Subjects that have participated in any other study in the last 3 months or plan to participate in another study at any time during this clinical trial.
15. Subjects that have foreign magnetic metal bodies or other conditions that render them unable to perform MRI.
16. Any other issue that, in the opinion of the investigator, makes the subject unsuitable for study participation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent AEs and treatment-emergent SAEs between D1 and M6 in IMP plus SOC compared to SOC alone.

Secondary endpoints 3

1. Absolute change in MAS and BPI from baseline to follow-up visits (M1, M3 and M6) in IMP plus SOC compared to SOC alone.
2. Difference in length of stay observed in IMP plus SOC compared to SOC alone regarding: a. Time spent in the ICU [defined as time from ICU admission to discharge from ICU]. b. Time spent in the hospital [defined as time from hospital admission to discharge from hospital].
3. Absolute change in ASIA Impairment Scale (AIS) – ISNCSCI standards – motor and sensory scores from baseline to follow-up visits (M1, M3 and M6) in IMP plus SOC compared to SOC alone.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Sponsor organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Address

Edificio Egas Monia Sala A8, Avenida Professor Egas Moniz Piso 2 Avenida Professor Egas Moniz Piso 2

City

Lisbon

Postcode

1649-028

Country

Portugal

Scientific contact point

Organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Contact name

Margarida Barreto

Public contact point

Organisation

Technophage Investigacao E Desenvolvimento Em Biotecnologia S.A.

Contact name

Margarida Barreto

Third parties 1

Locations

2 EU/EEA countries · 3 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 15 files

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

Application history

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