AMT-143 Hydrogel for Pain After Hernia Surgery

Overseen By Chief Executive Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AmacaThera Inc.

Must not be taking: Opioids, Antiarrhythmics, Sedatives, others

Disqualifiers: Chronic pain, Hypersensitivity, Heart issues, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is designed to evaluate the safety, efficacy, and pharmacokinetics (PK) of three ascending doses of AMT-143 to determine the appropriate dose of AMT-143 for the management of postsurgical pain following inguinal hernia repair. Healthy male and female participants ≥18 years of age scheduled for open inguinal hernia repair surgery will be enrolled. Participants will all receive general anesthesia. The open inguinal hernia repair will be performed by a participating surgeon and the study medication will be administered by the surgeon prior to wound closure. AMT-143 is provided as a hydrogel containing 385 mg/mL ropivacaine (on a ropivacaine HCl equivalence basis). AMT-143 hydrogel will be provided as pre-filled syringes for administration via instillation into the surgical site after surgery and prior to suture. This will be a randomized, single blind, placebo and active controlled, dose escalation study performed at one clinical site to determine optimal doses of AMT-143. The study will consist of 30 participants, 10 per dose. Participants will receive AMT-143, or saline placebo, or ropivacaine 1% solution. Participants will be blinded to treatment. All assessments up to 4 h will be performed in the hospital clinic setting. Post discharge follow-up for the study will be handled on an outpatient basis and will be conducted by a home nurse up to Day 21. The participant will return to the clinical site for a final End of Study visit on Day 28.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medications that might interact with ropivacaine, such as certain local anesthetics or antiarrhythmics, and you must not have taken any investigational products within 30 days before the study.

What data supports the effectiveness of the treatment AMT-143 Hydrogel for pain after hernia surgery?

Research on similar hydrogels, like those containing ketoprofen or ketorolac, shows they can provide long-lasting pain relief after surgery by slowly releasing pain-relieving drugs. These studies suggest that hydrogels can effectively manage postoperative pain and improve healing. ^{1 2 3 4 5}

Is AMT-143 Hydrogel safe for use in humans?

Research on a similar hydrogel used in rats showed it helped with pain and wound healing without mentioning any safety issues. However, this data is from animal studies, so human safety data is still needed. ^{1 5 6 7 8}

How does AMT-143 Hydrogel differ from other treatments for pain after hernia surgery?

AMT-143 Hydrogel is unique because it uses a biodegradable thermosensitive hydrogel to deliver pain relief directly at the surgical site, providing a sustained release of the pain medication ketorolac. This approach not only helps manage postoperative pain more effectively than traditional solutions but also promotes better wound healing by reducing inflammation and enhancing tissue repair. ^{1 9 10 11 12}

Research Team

James Paul, MD

Principal Investigator

McMaster University

Eligibility Criteria

This trial is for healthy adults over 18 who are scheduled for open inguinal hernia repair surgery. They must be able to receive general anesthesia and agree to post-surgery follow-up. People with conditions that might interfere with the study or pose a risk if they participate are not eligible.

Inclusion Criteria

Body mass index (BMI) ≤40.0 kg/m2

Provides voluntary written informed consent

I am 18 years old or older.

Exclusion Criteria

History of hypersensitivity or allergy to amide type local anaesthetics (lidocaine, bupivacaine, or ropivacaine)

Have a clinically significant abnormal clinical laboratory test value, according to the judgement of the investigator

Have a clinically significant 12-lead ECG abnormality, according to the judgement of the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMT-143 or placebo or active control during surgery for postsurgical analgesia

1 day

1 visit (in-person)

Post-discharge Follow-up

Participants are monitored for safety, efficacy, and PK assessments on an outpatient basis

21 days

Home visits by nurse

End of Study Follow-up

Final assessments conducted at the clinical site to evaluate safety and efficacy

7 days

1 visit (in-person)

Treatment Details

Interventions

• AMT-143

Trial Overview The trial is testing three doses of AMT-143, a hydrogel containing ropivacaine, against a placebo and regular ropivacaine solution for pain management after hernia surgery. It's randomized and single-blind, meaning participants won't know which treatment they get.

Participant Groups

Group I: active AMT-143 hydrogel Experimental Treatment 1 Intervention

6 participants in the first cohort will receive 1 mL AMT-143 hydrogel containing 385 mg ropivacaine. 6 participants in the second cohort will receive 2 mL AMT-143 hydrogel containing 770 mg ropivacaine. 6 participants in the third cohort will receive 3 mL AMT-143 hydrogel containing 1,155 mg ropivacaine

Group II: Ropivacaine solution Active Control 1 Intervention

2 participants in the first cohort will receive 5 mL Ropivacaine 10 mg 1% solution. 2 participants in the second cohort will receive 5 mL Ropivacaine 10 mg 1% solution. 2 participants in the third cohort will receive 5 mL Ropivacaine 10 mg 1% solution.

Group III: Placebo Placebo Group 1 Intervention

2 participants in the first cohort will receive 1 mL saline placebo. 2 participants in the second cohort will receive 1 mL saline placebo. 2 participants in the third cohort will receive 1 mL saline placebo.

Who Is Running the Clinical Trial?

AmacaThera Inc.

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

In a study involving 72 pediatric patients with acute thermal burns, there was no significant difference in pain relief between Burnaid hydrogel dressing and plasticised polyvinylchloride film, indicating that neither dressing provided a clear analgesic advantage.

The trial, conducted over one year, showed that both dressings resulted in similar pain scores, stress levels, and re-epithelialisation rates, suggesting that Burnaid hydrogel dressing may not be a more effective option for pain management in pediatric burn treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of a hydrogel dressing as an analgesic adjunct to first aid for the treatment of acute paediatric burn injuries: a prospective randomised controlled trial. Holbert, MD., Kimble, RM., Chatfield, M., et al.[2021]

References

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

Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model. [2018]

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

Biodegradable Amphipathic Peptide Hydrogels as Extended-Release System for Opioid Peptides. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Novel temperature-responsive hydrogel injected to the incision site for postoperative pain relief in laparoscopic abdominal surgery: a single-blind, randomized, pivotal clinical trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Early Efficacy of Intra-Articular HYADD® 4 (Hymovis®) Injections for Symptomatic Knee Osteoarthritis. [2020]

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

Novel strategy for the control of postoperative pain: long-lasting effect of an implanted analgesic hydrogel in a rat model of postoperative pain. [2013]

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

Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study. [2023]

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

Effectiveness of a hydrogel dressing as an analgesic adjunct to first aid for the treatment of acute paediatric burn injuries: a prospective randomised controlled trial. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration. [2017]

9. Switzerland pubmed.ncbi.nlm.nih.gov

The Controlled Release and Prevention of Abdominal Adhesion of Tannic Acid and Mitomycin C-Loaded Thermosensitive Gel. [2023]

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

Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats. [2022]

11. China pubmed.ncbi.nlm.nih.gov

[Preparation and roles of sliver-loaded viscous hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice]. [2021]

12. England pubmed.ncbi.nlm.nih.gov

A small study in healing rates and symptom control using a new sheet hydrogel dressing. [2011]