A Phase 2 Trial Evaluating the Effects of Thiethylperazine as diagnostic tool and therapeutic agent in Patients Diagnosed with an Early Stage of Alzheimer's disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immungenetics AG

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

completed 17 Dec 2025

Decision date (initial)

2022-11-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Pharmacokinetic, Therapy, Efficacy, Safety

To test the hypothesis that thiethylperazine (TEP) treatment for a
duration of 12 months improves Aβ clearance from the brain (compared
to placebo) in patients with MCI due to AD, or early dementia due to AD

Secondary objectives 4

1. Evaluate the diagnostic accuracy of TEP to differentiate/distinguish AD patients from disease controls
2. Evaluate the effect of TEP treatment vs. placebo on blood biomarkers of neurodegeneration
3. Evaluate the effect of TEP treatment vs. placebo on clinical progression of AD
4. Evaluate the effect of TEP treatment vs. placebo on CSF biomarkers of AD

Conditions and MedDRA coding

Newly diagnosed early-to-mild dementia due to Alzheimer's Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. For AD subjects only:
2. Florbetaben-PET no older than 12 months (at date of visit 2) with an SUVR above 1.44 (cut-off).
3. Newly diagnosed (< 12 months) mild cognitive impairment (MCI) due to Alzheimer’s disease or as classified by a Mini-Mental State Examination (MMSE) Score of ≤ 30 ≥ 20 reconfirmed at screening
4. Diagnosis of AD on the basis of the recommended examinations per the International Working Group (IWG) and the standard parameters/methodology of the respective clinical unit: o A Clinical Dementia Rating (global CDR) of 0.5 or 1. Memory box score must be at least 0.5. o Isolated or predominant episodic memory deficit, manifesting itself as either or both: ▪ Wechsler Memory Scale IV ≤ -1.5 SD below age-adjusted norm (Logical Memory subscale = Delayed Recall, Story A), ▪ ≤ -1.5 SD on the delayed recall trial of the CERAD word list (age-, sex- and education-adjusted performance)
5. Trial subject has full legal competence according to the investigator’s opinion
6. For trial subjects in disease control/reference (non-AD group) only:
7. Mini-Mental State Examination (MMSE) Score of ≤ 30 and ≥ 28 at screening. In case of MMSE score of ≤ 27, do NOT present with CSF biomarker profile and/or PET SUVR indicative of Alzheimer’s disease. If both are available but inconclusive, subjects are only eligible if PET SUVR is NOT indicative of AD
8. For AD subjects and disease controls:
9. Trial participants agree to APOE genotyping, or have a known APOE genotype (determined within the past 24 months).
10. Males and Females, aged ≥ 55 and ≤ 80 years
11. Willing and able to sign and date an Independent Ethics Committee-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be performed before the performance of any protocol-related procedures that are not part of the normal subject care
12. Willing and able to comply with scheduled study visits, treatment schedule, laboratory and cognitive testing, and other requirements of the study
13. Screening laboratory values must meet the following criteria and should be obtained within 6 weeks prior to entry into the trial: - Normal Full Blood Count (FBC, haematology) - Normal kidney function: serum creatinine < 1.5 X ULN - Normal hepatic function: Total bilirubin < 1.5 X ULN, Transaminases (ALT and AST) < 3 X ULN, Alk Phospatase < 2.5 X ULN - Normal prolactin - Fasting triglycerides < 2.5 X ULN
14. Subjects who are on the following concomitant medications are allowed into this trial ON THE CONDITION THAT they have been on a stable dose of these drugs for at least 3 months prior to study screening (and will continue to be on this stable dose): - acetylcholinesterase inhibitors - N-Methyl D Aspartate (NMDA) receptor antagonists
15. Subjects in this trial who are on the following medications/agents are obligated to comply with a wash-out period of 4 weeks prior to commencing screening for this trial: anticholinergic agents, Hypericum perforatum (St. John’s Wort) containing/derived drugs, oral corticosteroids, propranolol, metoprolol, clonidine, antihistamines other than cetirizine and EBSTEL® prior to screening must be completed
16. Good general health with no additional disease states that interferes with the trial according to the investigator’s assessment
17. Availability of an informant who is willing to provide information on the participant throughout the study period
18. Proficient/fluent in the German language

Exclusion criteria 29

1. For AD subjects and disease controls:
2. History of significant head trauma/brain injury with persistent neurologic defect(s) OR pre-existent known structural brain defect
3. History or evidence of other significant neurological diseases of the Central Nervous System (such as Parkinson's disease, multi-infarct dementia, frontotemporal dementia, Huntington's disease, normal pressure hydrocephalus, brain tumour, progressive supranuclear palsy, epilepsy, myasthenia gravis, subdural hematoma or multiple sclerosis)
4. Significant brain injury or abnormalities as demonstrated with neuro-imaging: pre-existent and/or diagnosed as per MRI (magnetic resonance imaging) scan(s), including evidence of cerebral infection, infarction (> 3 mm in size), brain tumours/ metastases/ leptomeningeal cancers (other than small meningiomas), or other focal lesions; the latter include multiple lacunas or lacunas in critical memory structure of the brain or severe confluent microvascular disease (but NOT mild white matter changes, which are frequent with ageing)
5. History or evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV)
6. History of a new cardiovascular event within the last 6 months
7. Resting sitting vital signs: Systolic blood pressure ≤ 100 mmHg or ≥ 165 mmHg, Diastolic blood pressure ≤ 60 mmHg or ≥ 100 mmHg, heart rate ≤ 50 beats/min or ≥ 90 beats/min
8. Clinically significant renal disease or insufficiency, including but not limited to creatinine value of >1.5 mg/dl
9. ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of normal laboratory range, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis) without enzyme elevation
10. Fasting triglycerides >2.5 times the upper limit of normal
11. Uncontrolled diabetes (fasting blood glucose [FBG] > 150 mg/dl)
12. Acute /current depression assessed by anamneses and a Geriatric Depression score > 5
13. Coagulopathy or any kind of anti-coagulant therapy (except Acetylsalicylic acid), that cannot be switched to monotherapy with Acetylsalicylic acid for one week before each CSF sampling.
14. Male and female subjects with reproductive potential who refuse to use adequate means of contraception from screening and up to 3 months after stopping treatment with TEP
15. Clinical relevant electrocardiogram (ECG) findings, abnormalities, e.g. pro-arrhythmic potential/effects on QT interval (QTc >450 msec for males, >470 msec for females, confirmed by manual assessment of ECG parameters)
16. Positive tested for hepatitis B surface antigen (HBsAg) or hepatitis C virus/antibodies (anti-HCV) for the first time within the last 6 months prior to the Screening Visit
17. Positive tested for human immunodeficiency virus (HIV) at Screening Visit
18. Extrapyramidal syndrome
19. Abnormal involuntary movement scale (AIMS) ≥ 2
20. Elevation of prolactin, e.g. subject with prolactin-dependent breast cancer or pituitary tumour
21. History of severe psychiatric disease like psychotic disorder or anxiolytic or neuroleptic therapy (for dementia-related or other psychiatric disorder) within the last 3 months of enrolment
22. Chronic depression or bipolar disorder or history of major depression within the past 2 years or history of any episode of treatment-resistant depression (requiring > 1 antidepressant, ECT etc.)
23. Significant history of alcohol abuse or drug abuse within the past 6 months (according to the investigator’s assessment)
24. Current treatment with TEP or treatment up to 24 months prior to screening
25. Known incompatibility of TEP or phenothiazines
26. Subject is receiving a treatment that may interact with TEP, e.g. adrenaline, tricyclic antidepressants, narcotics, bromocriptine, MAO inhibitors, CYP2D6 inhibitors, tramadol, pentetrazol, levodopa, anticonvulsants. Medication causing extrapyramidal symptoms increases the likelihood of central nervous system side effects.
27. Participation in an interventional trial involving another investigational drug within 4 weeks prior to screening visit
28. Women of childbearing potential not using adequate measures of contraception and women who are pregnant or nursing
29. Sensory impairment that prevents or significantly interferes with neuropsychological testing

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The 2 arms (TEP-THX vs. PBO-THX) will be compared as regards the mean change in Florbetaben-PET SUVR at month 12, adjusted for baseline

Secondary endpoints 4

1. Area under the curve (AUC), sensitivity and specificity for TEP-aided diagnosis at baseline (AD-DX vs. DC-DX)
2. Differences between the groups (TEP-THX vs. PBO-THX) as regards GFAP, p-Tau181, Aβ42/40 ratio and NfL biomarkers in plasma at month 12, adjusted for baseline
3. Differences between the groups (TEP-THX vs. PBO-THX) as regards Aβ42/40 ratio, p-Tau181/total Tau ratio, and NfL, at month 12, adjusted for baseline
4. Differences between the groups (TEP-THX vs. PBO-THX) as regards iADRS, ADCS-Cog 13, FCSRT, ADCS-iADL, QoL-AD, NPI-Q and GDS levels at month 12, adjusted for baseline

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immungenetics AG

Sponsor organisation

Immungenetics AG

Address

Eifflerstrasse 43, Altona-Altstadt Altona-Altstadt

City

Hamburg

Postcode

22769

Country

Germany

Scientific contact point

Organisation

Immungenetics AG

Contact name

Jonas Fischer

Public contact point

Organisation

Immungenetics AG

Contact name

Jonas Fischer

Third parties 4

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

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

Application history

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