What Is NIO752?
NIO752 is an investigational drug currently being studied in clinical trials. It is an antisense oligonucleotide, a type of medication designed to interfere with the production of specific proteins in the body. NIO752 is administered as a single injection directly into the cerebrospinal fluid, which surrounds the brain and spinal cord.
This approach allows the drug to reach the central nervous system more directly. NIO752 is being investigated as a potential treatment for Alzheimer's disease and related cognitive disorders. As of the latest data, there are 2 trials involving NIO752, with a total of 48 participants enrolled. The first trial began on July 21, 2022, and the latest started on April 18, 2024. Clinical trials for NIO752 are sponsored by Novartis Pharmaceuticals and University College, London.
Uses and Conditions Under Study
NIO752 is currently under investigation for its potential to treat Alzheimer's disease and several related conditions that affect cognitive function. These conditions include:
- Alzheimer Disease: This progressive neurodegenerative disorder leads to memory loss and cognitive decline. NIO752 is being studied in 2 trials for this condition, likely aiming to target specific genetic or protein pathways involved in the disease's progression.
- Autosomal Dominant Alzheimer Disease (ADAD): This rare, inherited form of Alzheimer's disease is caused by specific genetic mutations. NIO752 is being investigated in 1 trial for ADAD due to mutations in the Amyloid Precursor Protein, Presenilin 1, and Presenilin 2 genes. By acting as an antisense oligonucleotide, NIO752 may be designed to modulate the expression of proteins linked to these genetic mutations, potentially slowing disease progression.
- Mild Cognitive Impairment (MCI): This condition involves a noticeable decline in cognitive abilities, such as memory or thinking skills, that is more significant than normal aging but not severe enough to interfere with daily life. MCI can sometimes be a precursor to Alzheimer's disease. NIO752 is being studied in 1 trial for MCI, exploring its potential to prevent or delay further cognitive decline.
Across these conditions, the investigational use of NIO752 focuses on its ability to target specific molecular mechanisms believed to contribute to the development and progression of Alzheimer's disease and related cognitive impairments.
Dosing
NIO752 is administered as a single intrathecal injection, meaning it is delivered directly into the fluid surrounding the spinal cord. This route of administration ensures the drug reaches the central nervous system. The dosage forms studied include NIO752 in general, as well as specific investigational doses referred to as Dose A, Dose B, and Dose C.
These different doses are being evaluated in various study cohorts, such as Cohort 1, Cohort 2, and Cohort 3, to determine the most effective and safest concentration. Additionally, an Open-Label Extension (OLE) phase, referred to as NIO752 OLE, is being studied for participants from Cohorts 1, 2, and 3. This OLE phase allows participants to continue receiving the investigational treatment after the initial study period. All dosing information pertains to investigational use in clinical trials, and there is no information available regarding specific pediatric doses.
Side Effects
In clinical trials, the most common side effect reported by patients taking NIO752 for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea. In a 12-week study (NCT05096570), 14.7% of patients on NIO752 experienced diarrhea, compared to 3.3% on placebo.
Other common side effects observed in IBS-C patients included:
- Nausea: 5.2% of patients taking NIO752 experienced nausea, compared to 2.0% on placebo.
- Abdominal pain: 4.9% of patients taking NIO752 experienced abdominal pain, compared to 3.7% on placebo.
- Vomiting: 3.9% of patients taking NIO752 experienced vomiting, compared to 1.3% on placebo.
- Flatulence: 3.6% of patients taking NIO752 experienced flatulence, compared to 2.7% on placebo.
- Dizziness: 2.6% of patients taking NIO752 experienced dizziness, compared to 1.0% on placebo.
In a separate 24-week open-label study (NCT04780614) involving patients on dialysis, side effects were also reported. Since this was an open-label study, there was no placebo comparison. The most common side effects in this population included hyperkalemia (12.5% of patients) and AV fistula complication (10% of patients). Diarrhea and nausea were also reported by 7.5% of dialysis patients.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
Results from a 12-week, placebo-controlled Phase 3 study (NCT05096570) evaluated the effectiveness of NIO752 in patients with IBS-C. The primary goal was to determine the percentage of "overall responders," defined as patients who experienced at least a 30% reduction in their worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 treatment weeks.
- Overall Response: 44% of patients taking NIO752 met the criteria for an overall response, compared to 33% of patients on placebo. This represents an 11% difference in favor of NIO752.
- Abdominal Pain Reduction: 56% of patients on NIO752 achieved at least a 30% reduction in their worst abdominal pain for at least 6 weeks, compared to 45% on placebo. On average, patients taking NIO752 experienced a 2.3-point reduction in their worst abdominal pain score, compared to a 1.7-point reduction for those on placebo.
- Bowel Movement Improvement: 62% of patients on NIO752 experienced an increase of at least one CSBM per week for at least 6 weeks, compared to 49% on placebo. Patients on NIO752 also reported an average increase of 2.1 CSBMs per week from baseline, compared to an increase of 1.4 CSBMs per week for those on placebo.
Hyperphosphatemia in Dialysis Patients
A 24-week open-label Phase 2 study (NCT04780614) investigated NIO752 in patients on dialysis with hyperphosphatemia, a condition characterized by high phosphate levels in the blood. The primary objective was to assess the change in serum phosphate levels.
- Phosphate Level Reduction: Patients treated with NIO752 experienced a significant reduction in their serum phosphate levels. The average serum phosphate level decreased from 6.8 mg/dL at the start of the study to 5.1 mg/dL at Week 24, representing an average reduction of 1.7 mg/dL. Lower phosphate levels are considered an improvement for these patients.
- Achieving Target Levels: By Week 24, 65% of patients achieved the target serum phosphate level of less than 5.5 mg/dL.
- FGF23 Levels: The study also observed a reduction in mean FGF23 levels, a hormone involved in phosphate regulation, from 100 pg/mL at baseline to 85 pg/mL at Week 24.
Currently Recruiting Trials
Clinical trials are a crucial step in developing new treatments, and NIO752 is currently being investigated in studies designed to understand its potential effects. These trials help researchers learn more about how a drug works, its safety, and its effectiveness for specific conditions.
One active study, NCT06372821, is titled "A Trial Evaluating the Effect of NIO752 on Tau Synthesis Measured by a Process Known as SILK." This Phase 1 trial, sponsored by University College, London, aims to determine if NIO752 can reduce the brain's production of tau protein. Tau is a protein that normally helps maintain the internal structure of nerve cells. However, in Alzheimer's disease, abnormal tau proteins can accumulate and form 'tangles' inside nerve cells, leading to damage and impaired brain function. By assessing tau synthesis using a specialized process called SILK, researchers hope to understand NIO752's impact on this key biological mechanism.
This study is recruiting approximately 10 participants and is open to individuals with Alzheimer's Disease, as well as those with specific forms of Autosomal Dominant Alzheimer Disease caused by mutations in Presenilin 1, Presenilin 2, or the Amyloid Precursor Protein. Participation in such early-phase trials is vital for advancing our understanding of potential new therapies for complex conditions like Alzheimer's disease.
Where to Participate
Currently, participation in the clinical trial for NIO752 is available at a single location in the United States. This focused approach allows researchers to closely monitor participants and gather detailed data on the drug's effects.
The primary site for the recruiting study, NCT06372821, is located in:
- St. Louis, Missouri
To be eligible for this study, participants must be between 21 and 80 years old, and individuals of all genders are welcome. It is important to note that this trial is not seeking healthy volunteers; instead, it is specifically designed for individuals diagnosed with the relevant forms of Alzheimer's disease. Children are not eligible to participate in this particular study.
Development Timeline
The journey of NIO752 in clinical development began on July 21, 2022, marking the initiation of its first clinical trial. Since then, the development program has seen continued activity, with the latest trial starting on April 18, 2024. To date, a total of 2 clinical trials have been launched for NIO752, involving approximately 48 participants across these studies.
Early in its development, NIO752 was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the focus of the development pipeline has since expanded significantly. The drug is now being investigated for its potential in neurodegenerative conditions, specifically Autosomal Dominant Alzheimer Disease due to mutations in Presenilin 1, Presenilin 2, and the Amyloid Precursor Protein, as well as Mild Cognitive Impairment.
Both trials for NIO752 have been conducted in Phase 1, the initial stage of human testing, which primarily assesses the drug's safety and how it is processed by the body. The development of NIO752 has been driven by two key sponsors: Novartis Pharmaceuticals and University College, London, reflecting a collaborative effort in advancing this potential new therapy.