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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal amount of hyaluronidase, an enzyme that breaks down certain tissues, for use in filler injections. The focus is on ensuring the safety of these injections. Healthy individuals who can understand and consent to participate might be suitable candidates for this study. However, those with tattoos or scars on their upper arms or sensitivity to hyaluronic acid should not participate. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that hyaluronidase is likely to be safe for humans?

Research has shown that hyaluronidase is generally safe, though some people might experience side effects. The most common issues occur at the injection site, such as redness or swelling. Other possible side effects include headache, fatigue, nausea, and fever. Although rare, more serious reactions can include allergies.

Hyaluronidase is already used for other medical purposes, indicating its safety. However, individuals allergic to it should avoid its use. It is important to consult a healthcare provider about any concerns before starting treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Hyaluronidase is unique because it may enhance drug safety by breaking down hyaluronic acid, which can increase the dispersion and absorption of other drugs in the body. This means it has the potential to reduce adverse reactions and improve the efficacy of existing medications. Unlike standard treatments that don't modify drug absorption, hyaluronidase offers a novel approach by directly influencing the body's ability to process drugs more efficiently. Researchers are excited about this because it could lead to safer and more effective medication regimens, particularly for drugs that are currently limited by poor absorption profiles.

What evidence suggests that hyaluronidase might be an effective treatment for drug safety?

Research has shown that hyaluronidase has been safely used for over 50 years to enhance the spread and absorption of other drugs and fluids in the body. In this trial, participants will receive a dose of hyaluronidase to evaluate its safety and effectiveness. Studies confirm that recombinant human hyaluronidase, such as HYLENEX, meets specific standards in lab tests, effectively aiding in the absorption of other substances. Tests have found no negative effects on skin aging, fertility, or development. Overall, hyaluronidase is considered safe and helpful for improving the effectiveness of injections. ^{5 6 7 8 9}

Who Is on the Research Team?

Murad Alam, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12549492/

The Safety, Tolerability, and Pharmacokinetics of ALT-BB4 ... This study aimed to evaluate the safety, tolerability, and pharmacokinetics of ALT-BB4, a novel recombinant hyaluronidase derived from human ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168365924005200

The safety of recombinant human hyaluronidase PH20 in ... rHuPH20 anti-drug antibodies did not negatively alter fertility or development. Substantial safety margins were identified when compared to human-equivalent ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2005/021859_s000_Hylenex_Medr.pdf

Medical Review(s) - CPY Document - FDA The guidance confirmed that efficacy could be demonstrated by showing that the specific activity of HYLENEX recombinant meets the in vitro assay ...

4. withpower.com withpower.com/trial/early-phase-1-9-2012-a7276

Hyaluronidase for Drug Safety · Info for Participants 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 ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/17425247.2021.1981286

Safety of recombinant human hyaluronidase PH20 for ... Furthermore, preclinical data have shown no evidence of intrinsic skin aging affecting either the efficacy and safety of rHuPH20 or the reconstitution of HA in ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/021859s005lbl.pdf

HYLENEX recombinant (hyaluronidase human injection) The most frequently reported adverse experiences have been local injection site reactions. Hyaluronidase has been reported to enhance the adverse events ...

7. hylenex.com hylenex.com/important-safety-information/

Important Safety Information HYLENEX recombinant is contraindicated in patients with known hypersensitivity to hyaluronidase or any of the excipients in HYLENEX recombinant. Discontinue ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK545163/

Hyaluronidase - StatPearls - NCBI Bookshelf - NIH The most frequently encountered adverse effects are injection site reaction, headache, fatigue, nausea, and fever. Severe reactions can include hypersensitivity ...

9. halozyme.com halozyme.com/wp-content/uploads/Knowles-2021-Safety-of-recombinant-human-hyaluronidase-PH20-for-subcutaneous-drug-delivery.pdf

Safety of recombinant human hyaluronidase PH20 for ... Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery ... safety data from pregnant women treated with recombinant human.