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

• ClinicalTrials.gov Identifier: NCT04540900
• Recruitment Status: Recruiting
• First Posted: September 7, 2020
• Last Update Posted: August 16, 2021
• Sponsor: Krystal Biotech, Inc.
• Information provided by (Responsible Party): Krystal Biotech, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Skin Roughness; Wrinkle; Fine Lines; Skin Thickness	Biological: KB301; Other: Placebo	Phase 1

Detailed Description:

Up to thirty-seven (37) subjects divided into two (2) cohorts are planned for this Phase I study. Subjects enrolled in Cohort I will present a region of healthy buttock skin as a non-facial target area to receive two (2) injectable doses of KB301 (low or high). Cohort Ia will also present two regions of healthy buttock skin as a non-facial target area to receive two (2) injectable doses of KB301 (low or high) as well as a placebo injection. The objective of this cohort is to evaluate COL3A1 transgene expression (as measured by qRT-PCR of skin biopsies) and determine the optimal dose. Subjects enrolled in Cohort II will present with bilaterally symmetrical regions of moderate to severe fine lines and skin roughness as the target areas; these areas will be randomly assigned to receive either KB301 or a placebo to determine the extent of skin improvement in the KB301 arm. Throughout the study participants will complete questionnaires, have images captured of the target areas, undergo physical examinations, and have safety labs monitored.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 7, 2020
• Estimated Primary Completion Date: November 2021
• Estimated Study Completion Date: January 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: KB301; non-integrating HSV-1 vector expressing human type III collagen injection	Biological: KB301; non-integrating HSV-1 vector expressing human type III collagen injection
Placebo Comparator: Placebo; sterile isotonic saline injection	Other: Placebo; sterile isotonic saline injection

Outcome Measures

Primary Outcome Measures :

1. Assessment of the safety profile of KB301 by recording adverse events. [ Time Frame: 12 months ]
   The primary outcome will look at the safety of KB301 through the collection and quantification of adverse events. The Investigator will collect a description of the adverse event, time of onset, time of resolution, assess severity, and causal relationship to KB301.

Secondary Outcome Measures :

1. Evaluation of COL3A1 transgene expression 2-days post-dose. [ Time Frame: 12 months ]
   The secondary outcome measure in Cohort 1 will compare a KB301 injection site biopsy, to an area of untreated healthy buttock skin biopsy (at least 6 cm away from the sites of KB301 injection), via qRT-PCR analysis.
2. Assessment of skin roughness as compared to baseline, using the Skin Roughness Scale (SRS). [ Time Frame: 70 Days ]
   The secondary outcome measure in Cohort 2 will look at the mean change in the assessment of skin roughness as compared to baseline, using the Skin Roughness Scale (SRS). The SRS ranges from no fine lines (0) to extreme fine lines (4). A third-party independent blinded evaluator will perform the evaluations.
3. Assessment of fine line improvement as compared to baseline, using the Fine Lines Scale (FLS). [ Time Frame: 70 Days ]
   The secondary outcome measure in Cohort 2, will look at the mean change in the assessment of fine lines as compared to baseline, using the Fine Lines Scale (FLS). The FLS ranges from no texture (0) to diffuse texture (4). A third-party independent blinded evaluator will perform the evaluations.
4. Subject assessment of aesthetic improvement over baseline, using the Subject Satisfaction Scale (SSS). [ Time Frame: 70 Days ]
   The secondary outcome measure in Cohort 2, will look at the mean change in Subject's Satisfaction with the treatment per target area, as compared to baseline, using the Subject Satisfaction Scale (SSS), which is scored on a scale from 0 - 4, with 0 indicating not satisfied and 4 indicating excellent.
5. Assessment of skin fold thickness in Cohort 2. [ Time Frame: 70 Days ]
   The secondary outcome measure in Cohort 2, will look at the mean change in skinfold thickness of the non-facial target areas, using a caliper to measure, as compared to baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male or female in good general health, as determined by the Investigator, aged ≥18 and ≤75 at the time of consent.

2. Regions of suitable skin to be selected as Target Area(s), as determined by a physical examination conducted by the Investigator during the initial visit:

   1. Cohort 1 - single region of healthy buttock skin;
   2. Cohort 1a - bilaterally symmetric regions of healthy buttock skin at least 6 cm apart
   3. Cohort 2 - bilaterally symmetric regions of moderate to severe fine lines and skin roughness (score of 2 or 3), as determined by Investigator using the 5-point FLS and SRS on the cheeks above and below the zygomatic arch
3. A Fitzpatrick skin phototype score of I-IV.
4. A negative pregnancy test at the Study Day 0 Visit for subjects of child-bearing potential.
5. Signed and dated informed consent and willingness to attend all study visits and complete all procedures required by this protocol.

Exclusion Criteria:

1. Any transient or chronic skin condition, disorder, or infection within 20 cm of the Target Areas at Day 0 that, in the opinion of the Investigator, may confound study results.
2. History of laser treatment or chemical peels to the Target Areas within six months of the Study Day 0 Visit.
3. History of surgical procedures to Target Areas, including removal of benign or malignant skin cancers that, in the opinion of the Investigator, may confound study results.
4. Administration of a cosmetic and/or clinical research investigational agent, excluding KB301, at the location of the Target Areas within 3 months of the Study Day 0 Visit, that, in the opinion of the Investigator, may confound study results.
5. 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.
6. An active oral herpes infection at the Screening Visit or Study Day 0 Visit.
7. Women who are pregnant or nursing.
8. Subject who is unwilling to comply with contraception requirements per protocol.
9. A history of anaphylaxis or allergic reactions to any of the constituents of the product and/or local anesthetics.
10. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol, in the opinion of the Investigator.

Contacts and Locations

Contacts

Contact: Brittani Agostini; 412-586-5830; bagostini@krystalbio.com

Locations

United States, California

Steve Yoelin, MD Medical Associates, Inc.; Recruiting

Newport Beach, California, United States, 92663

Contact: Nubia Fernandez nubiaf19@gmail.com

Principal Investigator: Steve Yoelin, MD

Mission Dermatology; Recruiting

Rancho Santa Margarita, California, United States, 92688

Contact: Margarida Pinto gpinto.missionderm@gmail.com

Principal Investigator: Shireen V Guide, MD

United States, Florida

Skin and Cancer Associates, LLP. D/B/A Center for Clinical and Cosmetic Research; Active, not recruiting

Aventura, Florida, United States, 33180

Sponsors and Collaborators

Krystal Biotech, Inc.

More Information

• Responsible Party: Krystal Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT04540900
• Other Study ID Numbers: PEARL-1
• First Posted: September 7, 2020
• Last Update Posted: August 16, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Krystal Biotech, Inc.:

KB301; Wrinkles; Krystal Biotech

Additional relevant MeSH terms:

Depression; Behavioral Symptoms