A Multicenter, Randomized, Double-masked, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) Effects of NTRX-07 in Subjects with Mild Cognitive Impairment (MCI) or Mild to Moderate Alzheimer’s Disease (AD) (SPPN-AD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neurotherapia Inc.

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Apr 2025 → ongoing

Decision date (initial)

2025-01-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Neurotherapia Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Pharmacodynamic

To investigate the safety and tolerability as assessed by the number of adverse events of NTRX-07 administered for 28 days in patients with AD

Secondary objectives 1

1. To investigate the PK properties of NTRX-07 administered for 28 days in patients with AD

Conditions and MedDRA coding

Mild Cognitive Impairment (MCI)

Regulatory references

Scientific advice from competent authorities

National Centre For Public Health And Pharmacy

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Participants must be 65-80 years of age inclusive, at the time of signing the informed consent.
2. Clinical Dementia Rating (CDR) of 0.5 - 2.0; MMSE 12-26
3. pTau 217 consistent with AD, or recent amyloid test panel within 2 years. The test must be after any previous participation in an anti-amyloid MAB trial.
4. Participants who have been in a previous amyloid-directed MAB study must have a negative ARIA report after the study.
5. Confirmed medical documentation of AD symptoms onset at age 60 or later.
6. No active depression and a Geriatric Depression Score of < 6.
7. No change in acetylcholinesterase inhibitors or memantine for the previous six months and is not expected to start an acetylcholinesterase inhibitor during the duration of the study.
8. Living at home, with a reliable caregiver who sees them at least 3 times/week for 10 hours or more and can oversee the administration of the study drug.
9. Provide written informed consent and willingness as documented by a signed in-formed consent form; responsible caregiver must also provide written consent.
10. Body weight within 55-110 kg and body mass index (BMI) within the range 18-35 kg/m2 (inclusive)
11. Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days, after the last dose of study intervention: Refrain from donating sperm PLUS, either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. OR - Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant. - Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person. a. Female participants: - Must be a woman of nonchildbearing potential (WONCBP) (at least two years post-menopause or surgically sterile).

Exclusion criteria 28

1. Reported history or presence of clinically significant history of or cur-rent cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. Participants with stable, well-controlled conditions may be accepted upon review by the investigator and sponsor.
2. Presence of any contraindication to venous blood sampling for pharmacokinetic analyses.
3. Reported history of seizures, with the exception of childhood febrile seizures or metabolic seizures where the underlying etiology has resolved, and the participant has been seizure-free without treatment for at least 2 years.
4. Positive SARS-CoV-2 test, hepatitis panel (including hepatitis B surface antigen [HBsAg] or hepatitis C virus antibody [anti-HCV]), a positive HIV antibody screen or positive syphilis test.
5. Diagnosis of a dementia-related CNS disease other than AD (eg, Parkinson’s Disease, Huntington’s Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus)
6. Cannot tolerate spinal puncture procedure for cerebral spinal fluid (CSF).
7. Anticoagulation therapy that would contraindicate spinal puncture procedure for cerebral spinal fluid (CSF). Subjects on anti-coagulation therapy undergoing lumbar punctures: Subjects requiring ongoing anti-coagulation therapy should only be considered for screening and enrollment if the Principal Investigator (PI) determines it is safe to temporarily withhold anti-coagulation treatment in order to perform lumbar punctures. Before enrolling a subject on anti-coagulation therapy, the PI must confirm and docu-ment that withholding anti-coagulation for the lumbar puncture pro-cedure does not pose an undue risk to the subject.
8. Any contraindication to MRI (per facility standard of care).
9. Major structural brain disease by reported history or chart review (e.g., ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, severe micro-angiopathic disease, volume loss disproportionate for age or a single lesion in a critical region e.g., thalamus, hippocampus).
10. Findings on MRI demonstrating intracranial pathology as an alternative cause for cognitive impairment.
11. Any other reported history of central nervous system (CNS) trauma (e.g., contusion), or infections (e.g., human immunodeficiency virus [HIV], syphilis), that present active or residual effects on cognitive function.
12. Reported past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing. Specific medications listed in Section 9.9 concomitant therapy may be allowed.
13. Reported hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) that are deemed clinically significant by the PI or medical monitor.
14. Autoimmune disorders, active infections or other disorders, including the use of immunosuppressants, that may affect the subject’s immune system.
15. Reported current or chronic history of clinically significant liver disease. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-1 antitryp-sin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator.
16. Abnormal TSH, fT3 or fT4 at baseline screening. Subjects with known hypothyroidism or hyperthyroidism should be stable on treat-ment for 6 months prior to starting study and not anticipated to require any type of dose adjustment during the course of the study.
17. Reside in a nursing home or assisted care facility with the need for direct continuous medical care and nursing supervision. Participant may reside in such facilities provided continuous direct medical care is not required.
18. Subjects who require close or continual monitoring for self care or basic activities of daily living.
19. Subjects with history of psychiatric conditions such as schizophrenia and or bipolar disorder
20. Any reported history from the patient, family, or on supplied chart review or current suicide risk
21. Reported treatment with biological agents in the 3 months prior to dosing in this study, or within 5 half-lives of the biological agent prior to dosing.
22. Change of more than 2 points from screening MMSE to baseline MMSE, or discrepancy in disease classification between MMSE, and Trail Making test.
23. Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention.
24. Clinical laboratory findings outside the normal range and determined by the investigator or medical monitor to be clinically significant. These include but are not limited to: a. Alanine transaminase (ALT) or aspartate transaminase (AST) >1.5 x upper limit of normal (ULN) b. Total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%) c. QTcF >450 msec for male participants or >470 msec for female participants d. Positive drug/alcohol screen
25. Reported sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study
26. Reported regular use of known drugs of abuse within the past 3 years.
27. Inability to withhold CNS medications (e.g., benzodiazepines, stimulants) for 3 half-lives of the drug prior to cognitive testing and EEG administration.
28. Vaccination: Subjects should avoid receiving any vaccinations during the 28-day study period to minimize potential confounding effects from post-vaccination immune responses. Subjects must receive vac-cinations at least one month prior to the screening visit to ensure there is no acute-phase reaction that could impact study results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine the safety and tolerability in AD subjects following 28 days of administration of NTRX-07

Secondary endpoints 1

1. Plasma and CSF pharmacokinetics of NTRX-07

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neurotherapia Inc.

Sponsor organisation

Neurotherapia Inc.

Address

1500 Chagrin River Road

City

Gates Mills

Postcode

44040-7451

Country

United States

Scientific contact point

Organisation

Neurotherapia Inc.

Contact name

Chief Medical Officer (CMO)

Public contact point

Organisation

Neurotherapia Inc.

Contact name

Chief Medical Officer (CMO)

Third parties 3

Locations

3 EU/EEA countries · 7 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 21 files

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

Application history

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