NX-5948 Study in Healthy Subjects

Overseen By Allen Hunt, MD

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Nurix Therapeutics, Inc.

Disqualifiers: Psychiatric, Cardiovascular, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NX-5948 to understand how the body processes it. Researchers aim to determine how the drug is absorbed, metabolized, and eliminated. The trial involves a single group of healthy adult men receiving the treatment both intravenously and orally. Ideal participants are healthy, non-smoking males who have not used nicotine in the last three months and have a body mass index (BMI) between 18 and 30. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial is for healthy subjects with no significant medical history, it's likely that participants should not be on any regular medications.

Is there any evidence suggesting that NX-5948 is likely to be safe for humans?

Research is investigating the safety and tolerability of NX-5948 when administered through an IV or taken as a pill. Currently, specific safety information for healthy individuals is unavailable. However, other studies have shown NX-5948's potential in treating certain blood cancers.

For the IV form, studies aim to determine the appropriate dose to minimize side effects. For the pill form, research indicates it targets and breaks down specific proteins linked to cancer. Both forms remain in early testing stages, focusing primarily on safety before progressing to larger trials.

Phase 1 trials test a treatment in people for the first time. The main goal at this stage is to assess safety and the body's response. So far, NX-5948 appears well-tolerated, but further information is needed to confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NX-5948 because it offers a novel approach to treatment through dual delivery methods: both intravenously and orally. This flexibility could provide more personalized treatment options, accommodating different patient needs and preferences. Additionally, NX-5948 might feature a unique mechanism of action or a new active ingredient, which could potentially lead to more effective outcomes compared to standard treatments. These features combined suggest that NX-5948 could offer significant advancements in therapeutic effectiveness and patient convenience.

What evidence suggests that NX-5948 might be an effective treatment?

Research has shown that NX-5948 holds promise for treating certain blood cancers. Studies found that about 78% of patients with Waldenstrom's macroglobulinemia, a type of non-Hodgkin lymphoma, responded well to this treatment. NX-5948 works by breaking down BTK, a protein that aids cancer cell growth. Early findings also suggest effectiveness for patients with chronic lymphocytic leukemia. In this trial, participants will receive both the IV and pill forms of NX-5948. Overall, the evidence supports its potential effectiveness for these specific conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Sarah Injac, MD PhD

Principal Investigator

Nurix Therapeutics, Inc.

Are You a Good Fit for This Trial?

This clinical trial is open to healthy individuals. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have specific characteristics relevant to the study's objectives.

Inclusion Criteria

Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 at the screening visit

Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol

Subjects must follow protocol-specified contraception guidance as described in the protocol

Exclusion Criteria

I do not have any major health issues that could affect the study results or increase my risk.

History or presence of hypersensitivity, angioedema, or idiosyncratic reaction to the study drug(s) or related compounds

I am mentally capable and do not have significant emotional issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Period 1

Participants receive a single dose of NX-5948 by IV and undergo pre and post dose labs to assess PK and PD parameters

4-5 weeks

Multiple visits for clinical and laboratory evaluations

Period 2

Participants receive a single dose of NX-5948 by mouth. Pre and post dose blood, urine, and feces are collected until NX-5948 is no longer identified in samples

4-5 weeks

Multiple visits for clinical and laboratory evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NX-5948

Trial Overview The study is testing NX-5948, a new drug. It involves two periods: the first looks at how the drug affects the body (pharmacodynamics) and biomarkers; the second measures total radioactivity in the body and breaks down its components (metabolite profiling).

How Is the Trial Designed?

Group I: Active Treatment Arm IV and Oral Experimental Treatment 1 Intervention

This single Arm will include a single dose by IV and a single dose given by mouth for all 8 subjects.

Who Is Running the Clinical Trial?

Nurix Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,100+

Published Research Related to This Trial

SPH3127 demonstrated a dose-dependent increase in exposure and effectively suppressed plasma renin activity by up to 90% for 24 hours, indicating its potential efficacy in managing conditions related to renin activity.

The drug was well tolerated among healthy individuals, with only mild adverse events reported in 29.2% of single-dose and 33.3% of multiple-dose participants, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Jing, S., Xu, R., Yang, K., et al.[2021]

A single 10 mg dose of NRL001 administered as a suppository significantly reduced heart rate and diastolic blood pressure in 26 healthy elderly subjects compared to a placebo, indicating its potential cardiovascular effects.

The study found that NRL001 was well tolerated with a good safety profile, as most adverse events reported were mild and similar to those observed in younger volunteers in previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, controlled, crossover study to investigate the pharmacodynamics, pharmacokinetics and safety of 1R,2S-methoxamine hydrochloride (NRL001) in healthy elderly subjects. Bell, D., Duffin, A., Gruss, HJ., et al.[2014]

HTX-019, a new injectable formulation of aprepitant, has shown a tolerable safety profile in cancer patients when administered via both a 30-minute IV infusion and a 2-minute IV injection, with no treatment-emergent adverse events occurring within 30 minutes of administration.

In a study of 135 patients undergoing chemotherapy, both administration methods were well tolerated, and while some adverse events were reported during chemotherapy, none were directly related to HTX-019, indicating its potential as a safe option for preventing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crossover safety study of aprepitant: 2-min injection vs 30-min infusion in cancer patients receiving emetogenic chemotherapy. Navari, RM., Mosier, MC.[2020]

HTX-019, an NK-1 receptor antagonist, was found to be safe for cancer patients undergoing chemotherapy, with no treatment-emergent adverse events directly related to the drug during the study.

In a retrospective analysis of 100 patients, only five reversible adverse events were reported during treatment cycles, indicating a favorable safety profile for HTX-019 as part of an antiemetic regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of antiemetic prophylaxis with HTX-019 as a 30-min infusion in patients with cancer: a retrospective study. Perry, TS., Dickson, N., Patton, JF.[2020]

PD 0348292 was found to be well tolerated in healthy subjects during phase 1 studies, with only minor bleeding-related adverse events noted after multiple doses, indicating a favorable safety profile.

The drug demonstrated robust inhibition of thrombin generation in a concentration-dependent manner, suggesting its potential efficacy in managing coagulation, with pharmacokinetic properties supporting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and pharmacodynamics of PD 0348292, an oral, direct factor Xa inhibitor, after single and multiple dosings in healthy subjects. Xuan, D., McBride, S., Wastall, P., et al.[2018]

The study evaluated eight peptidylcyclodextrin compounds designed for drug targeting, confirming that their structural features were preserved and functional in binding to the NK1 receptor, with IC50 values ranging from 10^-9 to 10^-7 M.

These compounds effectively triggered a pharmacological response similar to the natural ligand, indicating their potential as targeted therapies for conditions involving NK1 receptor-expressing cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological in vitro evaluation of new substance P-cyclodextrin derivatives designed to drug targeting towards NK1-receptor bearing cells. Péan, C., Wijkhuisen, A., Djedaïni-Pilard, F., et al.[2019]

In a study involving 16 healthy male volunteers, the new memory-enhancing compound CL 275,838 showed a dose-related increase in plasma concentrations after 14 daily doses, indicating its pharmacokinetics are predictable and consistent.

The compound and its metabolites were well-tolerated, with no significant safety concerns noted during cognitive tests, suggesting potential for therapeutic action in enhancing memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple-dose pharmacokinetics and safety of a potential memory-enhancing compound, CL 275,838, in healthy male volunteers. Caccia, S., Confalonieri, S., Guiso, G., et al.[2019]

In a study involving 6 elderly patients (average age 84.5 years) with cerebrovascular disease, the cognitive enhancer aniracetam showed significantly increased half-life (t1/2) of its metabolites compared to young healthy volunteers, indicating altered metabolism in older adults.

Despite the prolonged serum levels of aniracetam metabolites, no clinical side effects were observed, suggesting that aniracetam may be safe for use in elderly patients with cerebrovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease. Endo, H., Tajima, T., Yamada, H., et al.[2019]

In a study involving 866 breast cancer patients undergoing moderately emetogenic chemotherapy, the NK(1)-receptor antagonist aprepitant was found to be more effective than a standard control regimen in preventing chemotherapy-induced nausea and vomiting (CINV), with a complete response rate of 50.8% compared to 42.5%.

Patients receiving aprepitant also reported a better quality of life regarding CINV, with 63.5% experiencing minimal or no impact on daily life, indicating that aprepitant not only reduces nausea and vomiting but also improves overall well-being during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. Warr, DG., Hesketh, PJ., Gralla, RJ., et al.[2022]

A new family of N-benzyltryptamines was synthesized and tested, revealing that while some compounds have high affinity for the 5-HT2A receptor, they generally act as full agonists at the 5-HT2C receptor, which could indicate potential psychedelic effects.

These compounds may have therapeutic applications beyond psychedelics, such as in treating weight loss, erectile dysfunction, drug abuse, or schizophrenia, due to their selective activation of the 5-HT2C receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-HT2 receptor binding, functional activity and selectivity in N-benzyltryptamines. Toro-Sazo, M., Brea, J., Loza, MI., et al.[2023]

Activation of CB(2) receptors using selective agonists can significantly reduce inflammation and improve neurological function in models of central nervous system injuries, such as multiple sclerosis and cerebral ischemia/reperfusion injury.

Combining CB(2) agonists with CB(1) antagonists not only reduces damage from these injuries but also enhances blood flow to the brain, indicating a promising therapeutic approach for conditions with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. Zhang, M., Martin, BR., Adler, MW., et al.[2023]

In a 2-year phase 3 study involving 1272 patients with relapsing-remitting multiple sclerosis, fingolimod therapy significantly reduced inflammatory lesion activity and brain volume loss compared to placebo, indicating its efficacy in managing the disease.

Fingolimod, particularly at the 0.5 mg dose, consistently showed benefits across various patient subgroups, leading to sustained reductions in both acute inflammatory activity and long-term tissue damage, supporting its role in improving long-term disease outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis. Radue, EW., O'Connor, P., Polman, CH., et al.[2020]

In a phase IIa clinical trial involving 97 comatose patients, the cannabinoid receptor agonist KN38-7271 showed improved survival rates within the first month after severe head injury compared to placebo, indicating potential early efficacy.

The treatment was found to be safe and well-tolerated, with no severe adverse effects reported, and it also resulted in less extreme intracranial pressure and cerebral perfusion pressure during the first week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early survival of comatose patients after severe traumatic brain injury with the dual cannabinoid CB1/CB2 receptor agonist KN38-7271: a randomized, double-blind, placebo-controlled phase II trial. Firsching, R., Piek, J., Skalej, M., et al.[2012]

VX15/2503 was found to be safe and well tolerated in a study involving 50 adult patients with multiple sclerosis, with no serious dose-limiting toxicities reported and only mild adverse events observed.

The pharmacokinetics showed that higher doses of VX15/2503 led to increased serum concentrations and prolonged effects, with significant cellular saturation lasting over 155 days, indicating potential for long-term therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety/tolerability of the anti-semaphorin 4D Antibody VX15/2503 in a randomized phase 1 trial. LaGanke, C., Samkoff, L., Edwards, K., et al.[2022]

Opicapone (OPC) demonstrated a dose-proportional increase in plasma exposure and effectively inhibited S-COMT activity by 79% to 95% in both healthy Chinese and Caucasian subjects, indicating its efficacy across different ethnicities.

The study found no significant safety concerns with OPC in healthy Chinese subjects, confirming its tolerable safety profile and suggesting that ethnicity does not significantly affect the pharmacokinetics and pharmacodynamics of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Pharmacodynamics, and Tolerability of Opicapone in Healthy Chinese and Caucasian Subjects: An Open-Label, Single-Center, Phase 1 Study. Cong, D., Song, J., Liu, Y., et al.[2022]

Citations

1. withpower.com withpower.com/trial/nx-5948-study-in-healthy-subjects-068ca

NX-5948 Study in Healthy Subjects · Info for Participants The available research does not provide specific data on the effectiveness of NX-5948 for its intended condition. The studies mentioned focus on other ...

2. ir.nurixtx.com ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-presents-positive-results-ongoing-clinical-0

Press releases NX-5948 demonstrated robust clinical activity with objective responses observed in 7 of 9 (77.8%) evaluable Waldenstrom's patients in the ongoing Phase 1a/1b ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05131022

A Study of NX-5948 in Adults With Relapsed/Refractory B- ... Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) B cell malignancies who ...

4. onclive.com onclive.com/view/nx-5948-demonstrates-preliminary-efficacy-in-high-risk-cll

NX-5948 Demonstrates Preliminary Efficacy in High-Risk ... NX-5948, a novel BTK degrader, has demonstrated promising early efficacy in patients with chronic lymphocytic leukemia (CLL), positioning it as a potential ...

5. ir.nurixtx.com ir.nurixtx.com/news-releases/news-release-details/nurix-therapeutics-presents-updated-positive-data-demonstrating

Press releases Nurix Therapeutics Presents Updated Positive Data Demonstrating Durable, Deepening Responses in Ongoing Clinical Trial of Bexobrutideg (NX-5948) ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/761388Orig1s000IntegratedR.pdf

761388Orig1s000 - accessdata.fda.gov The maintenance dose is then administered every 4 weeks by subcutaneous injection. Dosage is based on weight. Approved indication(s)/ population(s) (if ...

7. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper194839.html

Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) ... Primary objective: evaluate safety and tolerability of NX-5948 and establish maximum tolerated dose and recommended Phase 2 dose. Key ...