Intravenous ICVB-1042 for Pain

(ICVB-1042 Trial)

Recruiting at 9 trial locations

Overseen By IconOVir Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IconOVir Bio

Must not be taking: Antivirals, Vaccines, Steroids, others

Disqualifiers: CNS metastases, Cardiovascular abnormalities, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

17 Participants Needed

Trial Summary

What is the purpose of this trial?

Study to evaluate the safety and tolerability of intravenous ICVB-1042

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain treatments like biologics, major surgeries, or anti-viral agents within a specific time before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the idea that Intravenous ICVB-1042 for Pain is an effective treatment?

The available research does not provide specific data on the effectiveness of Intravenous ICVB-1042 for Pain. Instead, it discusses other treatments like intravenous ibuprofen and various nerve blocks for managing postoperative pain. Without direct evidence from the research, we cannot conclude that ICVB-1042 is effective for pain treatment based on the provided information. ^{1 2 3 4 5}

What safety data is available for ICVB-1042?

The provided research does not contain specific safety data for ICVB-1042 or any of its alternative names. The studies focus on different compounds and their effects, such as Venenum Bufonis, A-1048400, buprenorphine, ABT-102, and BIBN 4096 BS, none of which are directly related to ICVB-1042. ^{6 7 8 9 10}

Is the treatment ICVB-1042 a promising treatment for pain?

The information provided does not mention ICVB-1042 or its effectiveness, so we cannot determine if it is a promising treatment for pain based on the given research articles. ^{2 3 11 12 13}

Research Team

Julie Maltzman, MD

Principal Investigator

IconOVir Bio

Eligibility Criteria

This trial is for adults with advanced solid tumors that have worsened after treatment, including immune therapies and targeted drugs. Participants must have measurable disease, be relatively active (ECOG 0 or 1), and expected to live at least 3 more months. It's not for those who've had recent major surgery, significant heart issues, active infections needing strong meds, HIV/hepatitis B/C, blood cancers, need high-dose steroids or are pregnant/breastfeeding.

Inclusion Criteria

Life expectancy of at least 3 months

My cancer has returned or didn't respond to treatment, including immunotherapy and targeted therapy.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had any vaccines or antiviral drugs in the last 28 days.

I haven't taken any biologic treatments for my condition in the last 28 days or 5 half-lives, whichever is longer.

I am taking more than 10 mg/day of prednisone or a similar medication.

Treatment Details

Interventions

• ICVB-1042

Trial Overview The study tests the safety of a new drug called ICVB-1042 given through the veins to people with certain types of tumors. The main goal is to see how well patients tolerate this drug and what doses are safe.

Participant Groups

Group I: ICVB-1042 Experimental Treatment 1 Intervention

Part A: Dose escalation Part B: Dose expansion

Who Is Running the Clinical Trial?

IconOVir Bio

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

Intravenous ibuprofen (IVIB) at doses of 400 mg and 800 mg significantly reduced morphine consumption and improved pain relief in patients after abdominal or orthopedic surgery compared to a placebo, without increasing adverse events.

Both doses of IVIB provided similar analgesic effects and patient satisfaction scores, indicating that either dose can be effectively used for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic Efficacy of Intravenous Ibuprofen in the Treatment of Postoperative Acute Pain: A Phase III Multicenter Randomized Placebo-ControlledDouble-Blind Clinical Trial. Zhou, HS., Li, TT., Pi, Y., et al.[2023]

In a randomized controlled trial involving 48 patients undergoing video-assisted thoracoscopic surgery, continuous paravertebral (PV) catheter infusions significantly reduced maximum pain scores compared to single-shot intercostal blocks (ICB) during the 24 to 48 hours post-surgery (3.65 vs 6.44).

Patients receiving the PV catheter reported higher satisfaction with their pain management (74% satisfaction) compared to those with ICB (44% satisfaction), and they also used significantly less opioids (14.39 mg vs 30.50 mg morphine equivalents).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Paravertebral Catheter Versus Intercostal Blocks for Postoperative Pain Control in Video-Assisted Thoracoscopic Surgery: A Prospective Randomized Trial. Hutchins, J., Sanchez, J., Andrade, R., et al.[2018]

In a study of 50 patients undergoing video-assisted thoracic surgery (VATS), the continuous intercostal nerve block (ICB) using two catheters provided pain relief that was not significantly different from the paravertebral block (PVB) at 24 hours post-surgery, indicating comparable efficacy.

However, the study could not confirm that ICB is noninferior to PVB, suggesting that further improvements in ICB techniques may be needed for it to serve as a reliable alternative for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic effects of modified continuous intercostal block and paravertebral block under surgeon's direct vision after video-assisted thoracic surgery: a randomized clinical trial. Kadomatsu, Y., Mori, S., Ueno, H., et al.[2019]

In a study of 81 cancer patients experiencing severe pain, some patients developed a hyperexcited state that worsened with increasing doses of intravenous morphine, indicating a potential for opioid-induced hyperalgesia.

Switching from intravenous morphine to intravenous methadone was successful in managing pain for patients who did not respond to morphine, suggesting that methadone may be a viable alternative in cases of opioid-induced complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-induced hyperalgesia after rapid titration with intravenous morphine: Switching and re-titration to intravenous methadone. Mercadante, S., Ferrera, P., Arcuri, E., et al.[2015]

The multi-injection intertransverse process block provided non-inferior pain relief compared to the thoracic paravertebral block within 30 minutes after major breast cancer surgery, with similar worst resting pain scores.

Both techniques resulted in comparable recovery quality 24 hours post-surgery, indicating that the intertransverse process block is an effective alternative for managing postoperative pain in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between ultrasound-guided multi-injection intertransverse process and thoracic paravertebral blocks for major breast cancer surgery: a randomized non-inferiority trial. Zhang, H., Qu, Z., Miao, Y., et al.[2023]

Two novel compounds, A-686085 and A-1048400, effectively block N-type and T-type calcium channels, showing potential for pain relief without significant side effects; A-1048400 is particularly notable for not affecting blood pressure.

A-1048400 demonstrated robust pain relief in various pain models without altering psychomotor or hemodynamic functions, suggesting it could be a safer alternative for treating chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A-1048400 is a novel, orally active, state-dependent neuronal calcium channel blocker that produces dose-dependent antinociception without altering hemodynamic function in rats. Scott, VE., Vortherms, TA., Niforatos, W., et al.[2011]

BIBN 4096 BS, a new CGRP receptor antagonist for acute migraine treatment, demonstrated a favorable safety profile in a study involving 55 healthy volunteers, with no serious adverse events reported and only mild, transient side effects like paresthesias and fatigue.

The pharmacokinetics of BIBN 4096 BS showed dose-proportional plasma concentration increases, with a terminal half-life of approximately 2.5 hours, indicating effective dosing and clearance characteristics that support its potential use in migraine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers. Iovino, M., Feifel, U., Yong, CL., et al.[2021]

Cinobufagin (CBG), a compound isolated from Venenum Bufonis (VB), demonstrated stronger analgesic effects in pain tests compared to VB, indicating its potential as a more effective pain reliever.

CBG showed significantly less hepatotoxicity than VB, as evidenced by lower serum AST levels, while both compounds increased heart rate; however, CBG had a higher acute toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic and toxic effects of venenum bufonis and its constituent compound cinobufagin: A comparative study. Xu, L., Wang, S., Shen, H., et al.[2020]

Transdermal buprenorphine (TDB) demonstrated effective pain relief in dogs, with significant increases in thermal pain thresholds lasting beyond 36 hours after application, indicating its potential for long-term pain management.

In a study involving 10 healthy Beagles, TDB achieved peak plasma concentrations of buprenorphine, although some dogs showed no measurable levels, suggesting variability in absorption or metabolism among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs. Pieper, K., Schuster, T., Levionnois, O., et al.[2013]

ABT-102, a selective TRPV1 antagonist, demonstrated effective pharmacokinetics in healthy volunteers across three phase 1 studies, showing dose- and time-linear behavior with a half-life of 7 to 11 hours.

The studies confirmed that ABT-102 reaches steady state by day 5 of dosing, with a robust pharmacokinetic model indicating effective absorption and elimination, which is crucial for its potential use in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of the TRPV1 antagonist ABT-102 in healthy human volunteers: population analysis of data from 3 phase 1 trials. Othman, AA., Nothaft, W., Awni, WM., et al.[2013]

In a study of 90 patients with multiple rib fractures, thoracic paravertebral block (TPVB) provided significantly better pain relief compared to intravenous patient-controlled analgesia (IVPCA), as indicated by lower visual analogue scale (VAS) scores during rest and coughing.

TPVB also resulted in better preservation of pulmonary function, with higher oxygen levels and lung capacity measurements, and fewer complications compared to IVPCA, highlighting its efficacy in managing both pain and respiratory health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thoracic paravertebral block versus intravenous patient-controlled analgesia for pain treatment in patients with multiple rib fractures. Yeying, G., Liyong, Y., Yuebo, C., et al.[2018]

Intercostal nerve block (ICNB) provides significant immediate pain relief for patients with fractured ribs, as shown by a retrospective analysis of medical records, but its effectiveness diminishes over time.

For sustained pain management, especially in patients whose pain levels rise after ICNB, additional methods like intravenous patient-controlled analgesia or fentanyl patches are recommended to prevent complications and chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of intercostal nerve block for management of pain in rib fracture patients. Hwang, EG., Lee, Y.[2022]

In a study involving six dogs, ABT-116, a TRPV1 antagonist, did not consistently increase pain thresholds compared to buprenorphine, which showed greater analgesic efficacy in both thermal and mechanical pain assessments.

ABT-116 administration led to a significant increase in rectal temperature, indicating a potential side effect, while buprenorphine was more effective in providing pain relief without such temperature changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic efficacy of oral ABT-116 administration with that of transmucosal buprenorphine administration in dogs. Niyom, S., Mama, KR., De Rezende, ML.[2013]

References

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

Analgesic Efficacy of Intravenous Ibuprofen in the Treatment of Postoperative Acute Pain: A Phase III Multicenter Randomized Placebo-ControlledDouble-Blind Clinical Trial. [2023]

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

Ultrasound-Guided Paravertebral Catheter Versus Intercostal Blocks for Postoperative Pain Control in Video-Assisted Thoracoscopic Surgery: A Prospective Randomized Trial. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic effects of modified continuous intercostal block and paravertebral block under surgeon's direct vision after video-assisted thoracic surgery: a randomized clinical trial. [2019]

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

Opioid-induced hyperalgesia after rapid titration with intravenous morphine: Switching and re-titration to intravenous methadone. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Comparison between ultrasound-guided multi-injection intertransverse process and thoracic paravertebral blocks for major breast cancer surgery: a randomized non-inferiority trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A-1048400 is a novel, orally active, state-dependent neuronal calcium channel blocker that produces dose-dependent antinociception without altering hemodynamic function in rats. [2011]

7. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers. [2021]

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

Analgesic and toxic effects of venenum bufonis and its constituent compound cinobufagin: A comparative study. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of the TRPV1 antagonist ABT-102 in healthy human volunteers: population analysis of data from 3 phase 1 trials. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Thoracic paravertebral block versus intravenous patient-controlled analgesia for pain treatment in patients with multiple rib fractures. [2018]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Effectiveness of intercostal nerve block for management of pain in rib fracture patients. [2022]

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

Comparison of the analgesic efficacy of oral ABT-116 administration with that of transmucosal buprenorphine administration in dogs. [2013]