Gene Therapy for Skin Depressions

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

85 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment KB301 for skin depressions?

Research on gene therapy for skin conditions shows promise, as gene delivery systems have been developed to target skin cells effectively and sustain gene expression. This suggests that similar approaches could be beneficial for treatments like KB301, which may involve gene therapy techniques. ^{1 2 3 4 5}

Is gene therapy for skin conditions generally safe in humans?

Gene therapy for skin conditions, including the use of naked DNA injections, has been shown to be generally safe in humans, with no toxic effects reported in studies. This method allows genes to be expressed in skin cells and has potential for treating various skin disorders. ^{1 6 7 8 9}

How does the treatment KB301 differ from other treatments for skin depressions?

KB301 is unique because it uses gene therapy to target skin cells directly, potentially offering a long-term solution by correcting the underlying genetic issues, unlike other treatments that may only provide temporary relief. ^{2 3 10 11 12}

What is the purpose of this trial?

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Direct injection of naked DNA and cytokine transgene expression: implications for keratinocyte gene therapy. [2019]

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

Genetic correction of inherited epidermal disorders. [2012]

3. England pubmed.ncbi.nlm.nih.gov

Cutaneous gene transfer for skin and systemic diseases. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Durable and stratum-specific gene expression in epidermis. [2016]

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

An efficient gene transduction system for studying gene function in primary human dermal fibroblasts and epidermal keratinocytes. [2019]

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

KGF-1 for wound healing in animal models. [2012]

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

Advances in skin gene therapy. [2019]

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

Keratin 14-null cells as a model to test the efficacy of gene therapy approaches in epithelial cells. [2012]

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

Keratinocyte gene transfer and gene therapy. [2019]

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

Cutaneous gene transfer and therapy: the present and the future. [2012]

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

An approach to achieve long-term expression in skin gene therapy. [2015]

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

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