Safety, Tolerability and PK of a Single Subcutaneous Injection of XmAb27564 in Healthy Volunteers

Overseen By Ralph Zitnik, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Xencor, Inc.

Disqualifiers: Cardiovascular event, Viral infection, Asthma, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new protein treatment, XmAb27564, in healthy men and women to see if it is safe. The treatment aims to help with autoimmune diseases by changing how the immune system works.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy subjects with no significant health issues, it's possible that taking certain medications might exclude you from participating. It's best to discuss your specific medications with the trial coordinators.

What safety data exists for the treatment known as XmAb27564?

The research articles provided do not contain any safety data specifically for XmAb27564, Placebo, Control, or Dummy Treatment. They focus on the safety of temozolomide (TMZ) in various contexts, noting that TMZ can cause side effects like fatigue, blood cell count changes, and confusion, and that medication errors with TMZ can be serious or even fatal. ^{1 2 3 4 5}

Research Team

Ralph Zitnik, MD

Principal Investigator

Executive Medical Director, Clinical Development, Xencor

Eligibility Criteria

Inclusion Criteria

A nonsmoker for at least 12 weeks preceding screening

Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 45 days after administration of investigational product (IP).

Fertile male and female subjects must be willing to practice a highly effective method of birth control during and for 45 days after administration of IP and agree not to donate sperm from screening through 45 days after administration of IP.

Exclusion Criteria

Subjects with vital sign values outside the normal ranges

Subjects who are positive for MTB QuantiFERON, hepatitis B surface antigen, hepatitis C virus antibody, severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) by polymerase chain reaction (PCR)/antigen, or human immunodeficiency virus Type I or Type II tests at screening

Subjects who have evidence of any bacterial, viral, parasitic, or systemic fungal infections requiring treatment within the 21 days prior to randomization; or hospitalization due to infection within 3 months prior to randomization

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subcutaneous injection of XmAb27564 or placebo in a randomized, double-blind, placebo-controlled manner

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and pharmacokinetics after receiving the injection

4 weeks

Treatment Details

Interventions

• Placebo
• XmAb27564

Participant Groups

Group I: Single Ascending Dose - XmAb27564 Subcutaneous injection of Dose A, B, C, D, E or F Experimental Treatment 1 Intervention

Group II: Single Ascending Dose - Placebo Subcutaneous injection of placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

ICON Clinical Research

Industry Sponsor

Trials

52

Recruited

15,100+

Findings from Research

In a study involving 97 patients with malignant gliomas, temozolomide (TMZ) demonstrated a significantly higher response rate (35.71%) compared to lomustine (CCNU) (9.09%), indicating its greater efficacy in treating these aggressive brain tumors.

TMZ was found to have an acceptable safety profile, with common side effects being mild nausea and vomiting, suggesting it could be a preferred chemotherapy option for patients with refractory malignant brain gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. Qian, ZZ., Wang, HQ., Liu, XM., et al.[2018]

Temozolomide (TMZ) and the checkpoint kinase inhibitor AZD7762 both showed time- and concentration-dependent cytotoxic effects on human glioma cells, with their combination resulting in synergistic effects that enhance cell death.

The combination treatment of TMZ and AZD7762 not only suppressed the expression of the DNA repair protein MGMT but also modulated several signaling pathways, suggesting a complex mechanism that may improve the efficacy of glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells. Chen, Y., Tseng, BJ., Tsai, YH., et al.[2022]

In a phase I trial involving 38 patients with advanced solid tumors, the combination of intravenous methoxyamine (MX) and oral temozolomide (TMZ) was found to be safe, with no dose-limiting toxicities observed, allowing for a maximum tolerated dose of TMZ at 200 mg/m² daily for 5 days alongside MX at 150 mg/m² on day 1.

The trial showed that while there were some grade 3 and 4 adverse events, the combination therapy resulted in a partial response in one patient and prolonged stable disease in six others, suggesting potential efficacy in certain tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors. Eads, JR., Krishnamurthi, SS., Saltzman, J., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. [2018]

2. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Intranasal administration of temozolomide for brain-targeting delivery: therapeutic effect on glioma in rats]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Analyzing temozolomide medication errors: potentially fatal. [2021]