Gene Therapy for Skin Depressions

Not currently recruiting at 3 trial locations

Overseen By Shireen V Guide, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Krystal Biotech, Inc.

Disqualifiers: Skin conditions, Laser treatment, Surgery, others

Compensation: Varies

Number of Visits: Unknown

Duration: 65 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called KB301, which aims to improve the appearance of superficial skin depressions like wrinkles and fine lines. KB301 delivers type III collagen to the skin, potentially restoring the skin's structure and smoothness. Participants will receive either KB301 or a placebo (a harmless saline solution) to evaluate the treatment's effectiveness. Individuals with moderate to severe skin lines or wrinkles, particularly in specific facial areas, might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial investigator to get a clear answer.

Is there any evidence suggesting that KB301 is likely to be safe for humans?

Research has shown that KB301, a new gene therapy, is being tested for safety in treating skin depressions. In earlier studies, patients tolerated KB301 well, and no major safety issues emerged. The treatment uses a type of virus that cannot replicate or integrate with the body’s DNA, making lasting harm unlikely.

Some minor side effects, such as redness or swelling at the application site, have been noted. These effects are usually mild and resolve on their own. Ongoing research focuses on ensuring the treatment's safety for a broader population.

Overall, evidence so far suggests that KB301 is safe for human use, but further studies are needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for skin depressions, which often involve fillers or surgical interventions, KB301 utilizes a novel approach by employing a non-integrating HSV-1 vector to deliver human type III collagen directly to the skin. This innovative mechanism not only targets the root cause of skin depressions but also promotes natural collagen production, potentially offering longer-lasting results. Researchers are particularly excited about KB301 as it represents a shift towards using gene therapy to enhance skin health, potentially offering a less invasive and more sustainable solution.

What evidence suggests that KB301 might be an effective treatment for skin depressions?

Research shows that KB301, a gene therapy tested in this trial, might improve skin appearance by boosting type III collagen levels. Studies have found KB301 effective in reducing wrinkles and fine lines by increasing collagen in the skin. This therapy employs a safe delivery method that does not integrate with DNA, reducing potential risks. Early results suggest it could effectively treat shallow skin depressions. This method aims to naturally enhance the skin's strength and flexibility. Participants in this trial will receive either KB301 or a placebo to evaluate its effectiveness. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with healthy skin or mild to moderate wrinkles and roughness. Participants must have specific areas of skin suitable for treatment, not be pregnant or nursing, agree to contraception if applicable, and have no recent cosmetic procedures or conditions that could affect results.

Inclusion Criteria

I am in the group that involves healthy skin on my buttock.

My cheek area treated with a placebo is uneven compared to the area treated with KB301.

I have mild to moderate crow's feet wrinkles even when not moving my face.

Exclusion Criteria

I have been treated with KB301 before.

I am willing to follow the study's birth control requirements.

Any condition (including a history or current evidence of substance abuse or dependence) that, in the investigator's opinion, would impact subject's ability to complete all study-related procedures and/or poses an additional risk to the assessment of safety of the Investigational Product

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects receive injectable doses of KB301 or placebo, with assessments of COL3A1 transgene expression and skin improvement

65 days

Multiple visits for injections and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including durability assessments

3-4 months

Regular follow-up visits

Extension

Cohort 2 subjects may enroll in an extension phase if they have not reverted to baseline, with additional treatments and monitoring

3 months

What Are the Treatments Tested in This Trial?

Interventions

• KB301

Trial Overview The study tests KB301, a gene therapy designed to improve superficial skin depressions by expressing collagen. It's compared against a placebo in different cohorts based on the severity and location of their skin issues.

How Is the Trial Designed?

Group I: KB301 Active Control 1 Intervention

non-integrating HSV-1 vector expressing human type III collagen

Group II: Placebo Placebo Group 1 Intervention

sterile isotonic saline

Who Is Running the Clinical Trial?

Krystal Biotech, Inc.

Lead Sponsor

Trials

15

Recruited

770+

Published Research Related to This Trial

Electroporation of a KGF-1 plasmid into excisional wounds in rodent models significantly improved healing rates, with 92% of wounds healed by day 12 compared to only 40% in control groups.

The treatment also enhanced the quality of epithelialization and increased the density of new blood vessels, indicating that KGF-1 could be a promising approach to improve wound healing in conditions that typically impair it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KGF-1 for wound healing in animal models. Marti, GP., Mohebi, P., Liu, L., et al.[2012]

Researchers developed keratinocyte cell lines from patients with epidermolysis bullosa simplex (EBS) caused by K14-null mutations, which helps in understanding the disease mechanisms and testing new treatments.

By introducing wild-type K14 complementary DNA into these K14-null cells, they demonstrated that this gene therapy approach can significantly restore normal cell behavior, suggesting a potential pathway for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keratin 14-null cells as a model to test the efficacy of gene therapy approaches in epithelial cells. D'Alessandro, M., Coats, SE., Jonkmann, MF., et al.[2012]

The study presents a novel gene therapy method using a bicistronic retroviral vector to achieve long-term expression of therapeutic genes in skin cells, specifically targeting keratinocytes and fibroblasts to create genetically modified human skin equivalents.

By using topical colchicine treatment, researchers can selectively enrich keratinocyte stem cells that carry the desired genetic modifications, demonstrating a potential pathway for effective systemic delivery of therapeutic proteins through the skin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An approach to achieve long-term expression in skin gene therapy. Therrien, JP., Pfützner, W., Vogel, JC.[2015]

Intradermal injection of DNA allows for the expression of cytokine genes in keratinocytes, leading to significant biological effects in the skin, which could be beneficial for treating various skin conditions.

This method has shown to be safe and efficient in immunosuppressed animal models, suggesting that keratinocyte gene therapy could be a promising therapeutic approach for dermatological issues in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct injection of naked DNA and cytokine transgene expression: implications for keratinocyte gene therapy. Sawamura, D., Akiyama, M., Shimizu, H.[2019]

The skin is a promising target for gene therapy due to its unique properties and the ability to modify various cell types, which can help treat a wide range of diseases, including genetic disorders and infections.

Challenges in skin gene therapy include improving the efficiency of gene delivery methods, targeting specific skin cells like keratinocyte stem cells, and ensuring long-lasting and regulated gene expression for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in skin gene therapy. Pfützner, W., Vogel, JC.[2019]

Gene therapy has shown promising results in treating recessive skin diseases, achieving full phenotypic reversion in conditions like junctional epidermolysis bullosa and ichthyosis, using retroviral vectors to deliver corrective genes to skin cells.

There is potential for gene therapy to also address metabolic disorders through the transplantation of genetically modified skin cells, but successful trials will require improved methods for gene transfer and understanding the immune response to these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous gene transfer and therapy: the present and the future. Spirito, F., Meneguzzi, G., Danos, O., et al.[2012]

Gene therapy is advancing from research to clinical applications for treating inherited and acquired diseases, but challenges like transient gene expression and targeting stem cells still need to be addressed.

Epidermal and oral keratinocytes show promise as delivery vehicles for gene therapy due to their unique properties, such as the presence of stem cells and the ability to secrete therapeutic products, which can enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keratinocyte gene transfer and gene therapy. Garlick, JA., Fenjves, ES.[2019]

Genetic correction of skin disorders offers a promising alternative to current palliative treatments, focusing on the epidermis where many genetic skin diseases are found.

Research has progressed from lab studies to using human skin xenografts in immune-deficient mice, paving the way for future human trials in ex vivo gene therapy for skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic correction of inherited epidermal disorders. Khavari, PA.[2012]

Gene therapy has the potential to treat a variety of inherited and acquired skin diseases due to recent advancements in molecular genetics, making the skin an ideal target for these therapies.

To effectively implement cutaneous gene therapy, further improvements are needed in areas such as vector design, administration methods, immune response management, and gene expression regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous gene transfer for skin and systemic diseases. Khavari, PA., Rollman, O., Vahlquist, A.[2019]

A hybrid retroviral vector was developed to achieve targeted and long-term gene expression in the skin, specifically designed to express a reporter protein in keratinocytes, which are the primary cells in the epidermis.

In vivo studies in mouse skin showed that this vector can provide sustained and specific expression of the transgene in the upper layers of the epidermis, indicating its potential for effective gene therapy in treating skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable and stratum-specific gene expression in epidermis. Ghazizadeh, S., Doumeng, C., Taichman, LB.[2016]

Lentiviral vectors based on HIV provide over 90% gene transduction efficiency and sustained expression in primary human skin cells, significantly outperforming traditional methods that only achieve about 30% efficiency.

This high efficiency allows for clearer detection of gene effects, as demonstrated with migration control genes, making lentiviral systems a valuable tool for studying gene function in human skin cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An efficient gene transduction system for studying gene function in primary human dermal fibroblasts and epidermal keratinocytes. Chen, M., Li, W., Fan, J., et al.[2019]

Gene therapy targeting the skin has the potential to treat both local skin disorders and systemic diseases by utilizing the skin's ability to secrete therapeutic proteins, such as cytokines and interferons.

A novel in vivo method using pulsed electric fields has been developed to overcome the barrier of the stratum corneum, allowing for the delivery of naked reporter genes into the skin, demonstrating a promising approach for gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo skin-targeted gene delivery by pulsed electric fields. Zhang, L.[2011]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04540900

NCT04540900 | A Phase I Study of KB301, a Replication- ... A Phase I Study of KB301, a Replication-Incompetent, Non-Integrating Vector Expressing Human Type III Collagen (COL3) for the Treatment of Superficial Skin ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625001911

Progress in skin gene therapy: From the inside and out This commentary examines the current approaches of cell and gene therapies for genetic skin disorders. We write this from a local and systemic 'outside and ...

3. synapse.patsnap.com synapse.patsnap.com/article/jeune-aesthetics-reports-positive-phase-1-results-for-kb301-in-treating-wrinkles

Jeune Aesthetics Reports Positive Phase 1 Results for ... This research is examining KB301, an aesthetic treatment aimed at enhancing type III collagen (COL3) levels in the skin.

4. jeuneinc.com jeuneinc.com/publications/

Publications - Jeune Aesthetics Evaluating KB301, an Investigational COL3A1 Gene Delivery Treatment, for Improvement of Fine Lines and Wrinkles

5. biospace.com biospace.com/jeune-aesthetics-announces-phase-1-positive-interim-safety-and-efficacy-results-for-kb301-in-the-treatment-of-lateral-canthal-lines-and-dynamic-wrinkles-of-the-decollete

Jeune Aesthetics Announces Phase 1 Positive Interim ... KB301 is an investigational aesthetic therapy employing Krystal's novel replication-defective, non-integrating HSV-1-based vector to deliver two ...

6. ir.krystalbio.com ir.krystalbio.com/static-files/34c99c1b-1ebc-466a-b1ee-daa6cda3d2d3

First-in-Human Safety and Mechanism of Action (MOA) ... Vivo Gene Delivery for Directed Human Type III Collagen (COL3) Expression in Aesthetics ... of KB301 for the treatment of superficial skin depressions.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9287901/

New developments in the molecular treatment of ichthyosis developed a replication-defective herpes simplex virus type 1 (HSV-1) vector encoding human SPINK5 (KB104) for topical administration. HSV-1 can ...