NTRX-07 for people with Alzheimer's disease

A Multicenter, Randomized, Double-masked, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NTRX-07 in Subjects With Mild Cognitive Impairment or Mild to Moderate Alzheimer's Disease

This study will try NTRX-07, a new drug, in people aged 65–80 with mild cognitive impairment or mild to moderate Alzheimer's to check safety and how the drug moves through the body over 28 days.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 65 Years to 80 Years
• Sex: All
• Sponsor: NeuroTherapia, Inc. (Industry-sponsored)
• Locations: 6 sites (Brno and 5 other locations)
• Trial ID: NCT07058688 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study gives participants either NTRX-07 or placebo and follows them for a short 28-day period to monitor safety and drug behavior in the body. Investigators will collect blood and cerebrospinal fluid samples to measure drug levels and pharmacokinetics and will record any adverse events to judge tolerability. Eligible participants must have biomarker evidence of Alzheimer pathology (pTau217 or a recent amyloid test) and meet cognitive criteria consistent with MCI or mild to moderate AD. The study requires a reliable caregiver and stable background dementia medications for enrollment.

Who should consider this trial

Good fit: Ideal candidates are people aged 65–80 with mild cognitive impairment or mild to moderate Alzheimer's (MMSE 12–26), biomarker confirmation of AD (pTau217 or recent amyloid test), stable on dementia medications, and living at home with a reliable caregiver.

Not a fit: People with severe Alzheimer's, active depression, age outside 65–80, recent changes in acetylcholinesterase inhibitors or memantine, or without biomarker evidence of AD are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, NTRX-07 could offer a new, well-tolerated option that targets neuroinflammation and might help slow symptom progression in people with early Alzheimer's.

How similar studies have performed: Previous efforts targeting neuroinflammation in Alzheimer's have shown mixed or limited success, so this approach remains experimental and not yet proven to change disease course.

Eligibility criteria

Inclusion Criteria

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; and education-adjusted Logical Memory II scores consistent with MCI or mild to moderate AD (\<1.5 SD below mean cutoff). 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 informed 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 or Female • 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 ba sis) 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.

  * Female participants: Must be a woman of nonchildbearing potential (WONCBP) (at least two years post-menopause or surgically sterile).

Exclusion Criteria

1. Reported history or presence of clinically significant history of or current 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. Change of more than 2 points from screening MMSE to baseline MMSE, or discrepancy in disease classification between MMSE, and Trail Making test.
3. 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)
4. Cannot tolerate spinal puncture procedure for cerebral spinal fluid (CSF).
5. Anticoagulation therapy that would contraindicate spinal puncture procedure for cerebral spinal fluid (CSF).
6. Any contraindication to MRI (per facility standard of care).
7. 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 mi- microangiopathic disease, volume loss disproportionate for age or a single lesion in a critical region e.g., thalamus, hippocampus).
8. Findings on MRI demonstrating intracranial pathology as an alternative cause for cognitive impairment
9. 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.
10. 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.
11. Autoimmune disorders, active infections or other disorders, including the use of immunosuppressants, that may affect the subject's immune system.
12. 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 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator.
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. Abnormal TSH, fT3 or fT4 at baseline screening. Subjects with known hypothyroidism or hyperthyroidism should be stable on treatment for 6 months prior to starting study and not anticipated to require any type of dose adjustment during the course of the study.
15. 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.
16. Subjects who require close or continual monitoring for self care or basic activities of daily living.
17. Subjects with history of psychiatric conditions such as schizophrenia and or bipolar disorder
18. Any reported history from the patient, family, or on supplied chart re- view or current suicide risk
19. Patients may continue prior concomitant medications at the same sta ble dose. Drugs with potential interactions are detailed in the investi gator's brochure. Participants receiving drugs with strong interactions should be excluded where the drug in question cannot be safely stopped for an appropriate washout period pre-study and until 7 days after the last dose of study medication (completion of the post-study safety visit).
20. 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..
21. Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investiga- tional study intervention.
22. 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:

    1. Alanine transaminase (ALT) or aspartate transaminase (AST) \>1.5 x upper limit of normal (ULN)
    2. Total bilirubin \>1.5 x ULN (isolated bilirubin \>1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin \<35%)
    3. QTcF \>450 msec for male participants or \>470 msec for female participants
    4. Positive drug/alcohol screen
23. 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
24. Reported regular use of known drugs of abuse within the past 3 years.
25. Inability to withhold CNS medications (e.g., benzodiazepines, stimulants) for 3 half-lives of the drug prior to cognitive testing and EEG administration.
26. Presence of any contraindication to venous blood sampling for pharmacokinetic analyses.
27. Positive SARS-CoV-2 test, hepatitis panel (including hepatitis B sur face antigen \[HBsAg\] or hepatitis C virus antibody \[anti-HCV\]), a positive HIV antibody screen or positive syphilis test

Where this trial is running

Brno and 5 other locations

• Neuro Health Centrum s.r.o. — Brno, Czechia (Recruiting)
• Neuropsychiatrie s.r.o. — Prague, Czechia (Recruiting)
• Semmelweis University — Budapest, Hungary (Not_yet_recruiting)
• Semmelweis University — Budapest, Hungary (Not_yet_recruiting)
• Szpital Uniwersytecki W Krakowie — Krakow, Poland (Recruiting)
• Wrocławskie Centrum Alzheimerowskie — Wroclaw, Poland (Recruiting)

Study contacts

• Study coordinator: Joseph Foss, MD

Conditions Alzheimer Disease; Mild Cognitive Impairment; clinical pharmacology; neuroinflammation