A study of t04 in subjects with Alzheimer’s disease
| ISRCTN | ISRCTN15168684 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15168684 |
| Secondary identifying numbers | CA-18-09 |
- Submission date
- 20/01/2023
- Registration date
- 27/01/2023
- Last edited
- 15/07/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world. The aggregation of both amyloid beta (Aβ) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. Currently, there are no effective methods to stop the progression of AD. This study aims to investigate the functional effects of t04 on AD patients. One general possible molecular mechanism underlying the effect of t04 in the treatment of AD could be that the administered t04 rapidly passes through the BBB to reach the site of injury in AD. In these sites, t04 binds to local Aβ and other detrimental proteins (including aggregated proteins, denatured proteins and other conformationally abnormal proteins), such as fibrin, probably also colocalizes with plasminogen activator system, particularly tissue-type PA (tPA), that are locally expressed upon injury; hence, these PAs convert t04 and thus gets converted into active plasmin. Active products quickly degrades Aβ, fibrin and other detrimental proteins and cleaves nearby pro-BDNF or pro-NGF to generate their mature forms, which exert neuroprotective effects on damaged cholinergic neurons to promote their regeneration in the hippocampus and other areas. In addition, t04 further enters neurons to directly degrade the hyperphosphorylated intraneuronal Tau protein or indirectly improve its degradation by interacting with the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS). All these mechanisms contribute to the alleviation of neurodegeneration and eventually lead to cholinergic neuron regeneration and improvements in memory function in AD model mice and human patients.
Who can participate?
Patients with AD
What does the study involve?
This is an open-label, one-arm, non-randomized study. t04 is given to patients with AD for a treatment duration of 72 weeks.
What are the possible benefits and risks of participating?
Patients can get free medication, and through participation in this study, the memory function of the patients will be improved after t04. Considering the properties of t04, there may be the risk of bleeding, hypersensitivity Reactions and infection after receiving a t04 injection.
Where is the study run from?
Based on the condition of the patients, the intervention was performed at the home of patients or at Beijing Chang’an Chinese and Western Integrated Medicine Hospital.
When is the study starting and how long is it expected to run for?
August 2018 to September 2021
Who is funding the study?
Talengen Institute of Life Sciences (China)
Who is the main contact?
Ms Chunying Guo, guocy@talengen-pharma.com
Contact information
Public
Room C602G
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
| Phone | +86 15919440001 |
|---|---|
| guocy@talengen-pharma.com |
Principal Investigator
Room C602G
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
| Phone | +86 13810850852 |
|---|---|
| jnl@talengen-pharma.com |
Scientific
19 Zaolinqian St
Xicheng District
Beijing
100010
China
| Phone | +86 13811582746 |
|---|---|
| htzdm2011@163.com |
Study information
| Study design | Prospective interventional study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Home, Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A study of t04 in subjects with Alzheimer’s disease |
| Study objectives | t04 alleviates neurodegeneration and leads to cholinergic neuron regeneration and improvements in memory function in human patients with Alzheimer’s disease |
| Ethics approval(s) | Approved 05/09/2018, The Ethics Committee of Beijing Chang’an Chinese and Western Integrated Medicine Hospital (19 Zaolinqian St, Xicheng District, Beijing, China; +86-13522667371; 421337949@qq.com), ref: none provided |
| Health condition(s) or problem(s) studied | Alzheimer’s disease |
| Intervention | In this study, a treatment called t04 was given to patients with Alzheimer's disease. The treatment was given by clinical doctors or nursing staff with more than 5 years of experience and was administered face-to-face, either at the patient's home or at a hospital in Beijing. The study was open-label, meaning that everyone involved knew what treatment was being given, and it was not a randomized study. The treatment was given for 72 weeks using an intravenous injection at a dose of 50-200 mg, given 1-3 times a day. Sometimes, an atomization inhalation treatment was also used alongside the injection. The effectiveness of the treatment was measured by trained evaluators who assessed the patient's memory function using the Minimum Mental State Examination (MMSE). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Plasminogen |
| Primary outcome measure | Memory function measured using the Minimum Mental State Examination (MMSE) test at baseline and 2, 6, 10, 22 and 46 weeks |
| Secondary outcome measures | Adverse events measured using blood routine tests, blood biochemistry, coagulation function, hemolysis function, routine urine test, 12 lead ECG, physical examination, and vital signs, etc at baseline and 22 and 46 weeks |
| Overall study start date | 05/08/2018 |
| Completion date | 01/09/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 50 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 20 |
| Total final enrolment | 6 |
| Key inclusion criteria | 1. Written informed consent/assent obtained prior to any assessment performed 2. Age 50 to 100 years old (including 50 and 100 years old), male or female 3. Meet the diagnostic criteria of "likely ad dementia" of the National Institute on aging Alzheimer's disease association (NIA-AA) (2011) 4. The subjects are primary school graduates/graduates and above, and have the ability to complete the cognitive ability test and other tests specified in the program 5. Memory loss lasted for at least 6 months and tended to worsen gradually 6. Subjects with mild or moderate illness: 0 ≤ total score of MMSE ≤ 26 7. Total score of Clinical Dementia Rating Scale (CDR): Mild dementia: CDR = 1.0; Moderate dementia: CDR = 2.0 |
| Key exclusion criteria | 1. Dementia caused by other reasons: vascular dementia, central nervous system infection, Creutzfeldt Jakob disease, Huntington's disease, Parkinson's disease, Lewy body dementia, traumatic dementia, other physical and chemical factors (such as drug poisoning, alcoholism, carbon monoxide poisoning, etc.), important physical diseases (such as hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space occupying lesions (such as subdural hematoma, brain tumor), endocrine disorders (such as thyroid disease, parathyroid disease), and vitamin B12, folic acid deficiency or any other known cause; 2. Have suffered from central nervous system diseases (including stroke, optic neuromyelitis, epilepsy, etc.); 3. Subjects who were diagnosed with psychiatric disorders according to DSM-V criteria, including schizophrenia or other mental diseases, bipolar disorder, severe depression or delirium; 4. Abnormal laboratory indexes: liver function (ALT and AST) exceeded 1.5×ULN, renal function (CR) exceeded 1.5×ULN, and creatine kinase exceeded 2×ULN; 5. Untreated hypertensive and hypotensive subjects at screening, or hypertensive subjects with uncontrolled hypertension after treatment; subjects with good blood pressure control after treatment can be determined by the investigator to be suitable for inclusion in this study; 6. Within 1 month of the screening visit, the subject has new or ongoing unstable or serious heart, lung, liver, kidney and hematopoietic diseases according to the judgment of the researcher, and does not meet the conditions for clinical research; 7. Clinically, people with significant allergic reaction history, especially drug allergy history, or known allergy to this product and its excipients; 8. Dyspepsia, esophageal reflux, gastric bleeding or peptic ulcer disease, frequent heartburn (≥ once a week) or any surgical operation that may affect drug absorption (such as partial/total gastrectomy, partial/total small bowel resection and cholecystectomy) within 6 months before screening 9. Alcohol or drug abusers 10. Human immunodeficiency virus antibody (ant HIV) and Treponema pallidum antibody (ant TP) are positive 11. Those who are currently using and cannot stop using drugs for Alzheimer's disease 12. Female subjects with positive pregnancy test or lactation and subjects unable to take effective contraceptive measures or have family planning 13. Participated in other clinical trials within 3 months before the screening visit 14. There are other situations that the researcher believes are not suitable for participation in this study |
| Date of first enrolment | 05/10/2018 |
| Date of final enrolment | 05/10/2020 |
Locations
Countries of recruitment
- China
Study participating centres
Xicheng District
Beijing
100010
China
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
Sponsor information
Research organisation
Room C602G
289 Digital Peninsula
Shunfeng Industrial Park
No.2 Red Willow Road
Futian District
Shenzhen
518000
China
| Phone | +86 15919440001 |
|---|---|
| gexj@talengen-pharma.com |
Funders
Funder type
Research organisation
No information available
Results and Publications
| Intention to publish date | 31/10/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Ms Chunying Guo, guocy@talengen-pharma.com. The type of data that will be shared comprises a table showing the scoring records, clinical observation record forms, images, videotapes, and detection data. Dates of availability: 05/10/2023 to 05/10/2033. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 27/01/2023 | No | No |
Additional files
Editorial Notes
15/07/2025: The word 'plasminogen' was replaced with the word 't04' in the public title, scientific title, study objectives, interventions and the Plain English summary of protocol.
14/11/2023: The following changes were made to the trial record:
1. The recruitment start date was changed from 05/01/2019 to 05/10/2018.
2. The recruitment end date was changed from 05/10/2023 to 05/10/2020.
3. The overall end date was changed from 10/10/2023 to 01/09/2021.
4. The plain English summary was updated to reflect these changes.
29/03/2023: Internal review.
02/02/2023: The ethics details were updated.
27/01/2023: Trial's existence confirmed by the Ethics Committee of Beijing Chang’an Chinese and Western Integrated Medicine Hospital.
