Hyaluronidase for Drug Safety

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwestern University

Must not be taking: Accutane

Disqualifiers: Pregnancy, Mental illness, Scarring, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

5 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it does exclude those who have used Accutane in the past 6 months.

What data supports the effectiveness of the drug Hyaluronidase for drug safety?

Recombinant human hyaluronidase has been used safely for over 50 years to help other drugs and fluids spread and absorb better in the body. It is a purer form than older versions, reducing the risk of allergic reactions, and has been approved by the US FDA for facilitating fluid administration. ^{1 2 3 4 5}

Is Hyaluronidase safe for use in humans?

The provided research articles do not contain specific safety data on Hyaluronidase or its variants like Human Recombinant Hyaluronidase, Hyalase, Vitrase, Amphadase, or Hydase. ^{6 7 8 9 10}

How does the drug hyaluronidase differ from other treatments for this condition?

Hyaluronidase, specifically the recombinant human form, is unique because it is a purer, human-derived enzyme that reduces the risk of allergic reactions compared to traditional animal-derived versions. It is used to enhance the absorption and dispersion of other drugs when administered subcutaneously, making it a safer and more effective option for facilitating drug delivery. ^{2 4 5 11 12}

What is the purpose of this trial?

The purpose of this study is to find how much hyaluronidase should be used when receiving injections of fillers.

Research Team

Murad Alam, MD

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for adults over 18 in good health who can give informed consent. It's not for those with a tendency to form abnormal scars, tattoos or scars where the treatment will be given, allergies to hyaluronic acid, under 18s, pregnant or breastfeeding individuals, those unable to understand the study or give consent, and anyone who has used Accutane recently.

Inclusion Criteria

I am willing and able to give consent for my tissue use and communicate with my doctor.

I am in good health overall.

Exclusion Criteria

I understand the study and can give my consent.

I have not used Accutane in the last 6 months.

Subjects with known hypersensitivity to hyaluronic acid

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive injections of hyaluronidase to determine appropriate dosing for reducing and removing hyaluronic acid filler

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hyaluronidase

Trial Overview The study is testing how much hyaluronidase should be used to reduce or remove hyaluronic acid fillers safely. Hyaluronidase is an enzyme that breaks down filler material injected into the skin.

Participant Groups

Group I: Dose of Hyaluronidase Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

A novel recombinant hyaluronidase was developed that matches the catalytic activity of existing commercial bovine-derived enzymes, which can enhance drug transport by breaking down hyaluronan barriers.

The new enzyme features a simplified purification process using Ni2+ affinity chromatography, making it easier to produce and potentially safer for clinical use, as it avoids risks associated with bovine-derived products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a New Type of Recombinant Hyaluronidase Using a Hexahistidine; Possibilities and Challenges in Commercialization. Park, C., Song, YK., Kim, YH., et al.[2019]

Hylenex recombinant, a new formulation of human hyaluronidase, has been shown to be safe and well tolerated in a study with 100 volunteers, with no allergic reactions reported after intradermal injections.

This recombinant version is expected to have lower allergic and immunological risks compared to traditional animal-derived hyaluronidases, supporting its approval by the US Food and Drug Administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment and implication of the allergic sensitivity to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-controlled clinical trial. Yocum, RC., Kennard, D., Heiner, LS.[2007]

In a pilot study involving 15 healthy volunteers, lactated Ringer's (LR) solution was found to cause significantly less infusion-site discomfort compared to normal saline (NS), with average pain scores of 9.4 mm for LR versus 20.0 mm for NS on a 100-mm scale.

All participants preferred LR over NS for subcutaneous infusions, and while both solutions were generally well tolerated, the incidence of mild adverse events was higher with NS, suggesting LR may be a better option for rHuPH20-facilitated fluid administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the tolerability of recombinant human hyaluronidase + normal saline and recombinant human hyaluronidase + lactated ringer's solution administered subcutaneously: A phase IV, double-blind, randomized pilot study in healthy volunteers. Dychter, SS., Ebel, D., Mead, TR., et al.[2021]

BIOBADASER, the Safety Register of the Spanish Society of Rheumatology, has successfully served as a template for creating other safety registers, such as BIOBADAMERICA and BIOBADADERM, highlighting its influence in standardizing data collection in rheumatology and beyond.

While template registers like BIOBADASER improve data collection and communication of safety concerns, they also face challenges in merging rare data and making comparisons across different registers due to their varied structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BIOBADASER, BIOBADAMERICA, and BIOBADADERM: safety registers sharing commonalities across diseases and countries. Carmona, L., de la Vega, M., Ranza, R., et al.[2017]

The BIOBADASER III registry, initiated in December 2015, includes data from 2,664 patients with rheumatic diseases treated with biological or synthetic drugs, focusing on tracking adverse events and treatment effectiveness.

In the first year, the most common adverse events reported were infections and infestations, highlighting the need for ongoing monitoring of safety in patients undergoing long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objectives and methodology of BIOBADASER phase iii. Sanchez-Piedra, C., Hernández Miguel, MV., Manero, J., et al.[2021]

The study found a high overlap of safety signals (SDRs) among the EudraVigilance Data Analysis System (EVDAS), FAERS, and VigiBase® databases, with median overlaps of 85% at the Preferred Term level and up to 97.7% when combining High Level Terms with Standardized MedDRA® Queries.

Despite the high overlap, the recall of signals in EVDAS was only about 59.4% to 87.9% of all signals generated across the databases, indicating that while the databases share many similar safety profiles, there are still differences in reporting that can affect signal detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase&#174;. Vogel, U., van Stekelenborg, J., Dreyfus, B., et al.[2021]

A Phase I study involving 24 healthy volunteers found that intravenous administration of rHuPH20 (up to 30,000 U) was well tolerated, with no serious adverse events reported, indicating a favorable safety profile.

The pharmacokinetics showed that rHuPH20 was rapidly cleared from the plasma, with plasma hyaluronan concentrations increasing in a dose-dependent manner and returning to baseline within one week, suggesting effective metabolism and clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Hyaluronidase PH20 Administered Intravenously in Healthy Volunteers. Printz, MA., Dychter, SS., DeNoia, EP., et al.[2022]

References

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

Development of a New Type of Recombinant Hyaluronidase Using a Hexahistidine; Possibilities and Challenges in Commercialization. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Recombinant human hyaluronidase PH20-mediated dermal spreading activity in mice is not altered by steroids, antihistamines, or salicylic acid. [2021]

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

Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage. [2021]

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

Assessment and implication of the allergic sensitivity to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-controlled clinical trial. [2007]

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

Comparison of the tolerability of recombinant human hyaluronidase + normal saline and recombinant human hyaluronidase + lactated ringer's solution administered subcutaneously: A phase IV, double-blind, randomized pilot study in healthy volunteers. [2021]

6. China pubmed.ncbi.nlm.nih.gov

[Analysis and Study of Adverse Event about Ophthalmic Sodium Hyaluronate Gel]. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

BIOBADASER, BIOBADAMERICA, and BIOBADADERM: safety registers sharing commonalities across diseases and countries. [2017]

8. Spain pubmed.ncbi.nlm.nih.gov

Objectives and methodology of BIOBADASER phase iii. [2021]

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

Drug-Induced Rhabdomyolysis Atlas (DIRA) for idiosyncratic adverse drug reaction management. [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase&#174;. [2021]

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

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Hyaluronidase PH20 Administered Intravenously in Healthy Volunteers. [2022]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Isolation and purification of bovine testicular hyaluronidase]. [2006]