RhPDGF-BB for Perianal Fistula Healing

Overseen By Cyndi R Clark, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alexander Hawkins

Disqualifiers: Genito-urinary fistulization, Major GI surgery, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 7

Duration: 6 months

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The average success rate for healing and remission of complex perianal fistulas, idiopathic or Crohn's-related, is approximately 50%. These abnormal connections between the rectum and the outside skin remain a major clinical challenge in need of new treatments aimed at tissue repair. Platelet-derived growth factor drives wound healing and tissue regeneration, and manufactured PDGF is currently used to heal diabetic foot ulcers and regenerate bone in periodontal and orthopedic patients. Manufactured recombinant human PDGF has the potential to improve the success rate for complete healing of complex perianal fistulas, reduce the recurrence rate due to reopening of the fistula tract, and avoid complications associated with routine surgical interventions.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently enrolled in another drug or device trial, you must wait 30 days after the last investigational treatment before participating in this trial.

What data supports the effectiveness of the treatment RhPDGF-BB for perianal fistula healing?

Research shows that RhPDGF-BB is effective in promoting wound healing and tissue regeneration in various conditions, such as periodontal defects and chronic diabetic foot ulcers, by stimulating cell growth and tissue repair. ^{1 2 3 4 5}

Is RhPDGF-BB safe for use in humans?

Research shows that RhPDGF-BB is generally safe for humans, with studies indicating it is biocompatible and has no systemic or local toxicity when used alone or with other materials, supporting its safe use in wound healing. ^{1 6 7 8 9}

How is the drug RhPDGF-BB unique in treating perianal fistulas?

RhPDGF-BB is unique because it is a growth factor that stimulates the healing process by promoting the growth and movement of cells needed for tissue repair, which is different from traditional treatments that may not directly enhance cellular regeneration. ^{1 2 3 5 7}

Research Team

Alexander T Hawkins

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for individuals with complex perianal fistulas, which can be idiopathic or related to Crohn's disease. Participants should have a history of these fistulas that are difficult to heal and may have tried other treatments without success.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

I currently have a draining seton in place for my fistula.

Willing and able to provide informed consent and to comply with study protocol and follow-up

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the trial.

I have cancer at the site where the treatment will be applied.

I have an abnormal connection between my genital and urinary tracts.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Procedure

Participants are randomized and scheduled for the baseline procedure, including seton placement and initial assessment

1 week

1 visit (in-person)

Treatment

Participants receive either the rhPDGF-BB-enhanced collagen plug or routine care, followed by assessments at 1, 3, and 6 months

6 months

3 visits (in-person) at 1, 3, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for fistula healing and recurrence

6 months

3 visits (in-person) at 1, 3, and 6 months

Open-label Extension (optional)

Participants in the control arm with non-healing fistulas at 3 months may crossover to receive the investigational intervention

3 months

Treatment Details

Interventions

• RhPDGF-BB

Trial Overview The study is testing RhPDGF-BB, a manufactured protein known to aid in wound healing and tissue regeneration. It's being used in the form of an enhanced collagen plug inserted into the fistula tract to promote healing.

Participant Groups

Group I: rhPDGF-BB-enhanced collagen plug Experimental Treatment 1 Intervention

Participants receive collagen plug saturated with rhPDGF-BB.

Group II: Routine care Active Control 1 Intervention

Participants receive routine care for their fistula.

RhPDGF-BB is already approved in United States, European Union for the following indications:

Approved in United States as rhPDGF-BB for:

• Diabetic foot ulcers
• Periodontal bone regeneration
• Orthopedic bone regeneration

Approved in European Union as rhPDGF-BB for:

• Diabetic foot ulcers
• Periodontal bone regeneration

Who Is Running the Clinical Trial?

Alexander Hawkins

Lead Sponsor

Trials

1

Recruited

10+

Lynch Regenerative Medicine, LLC

Collaborator

Trials

2

Recruited

50+

Findings from Research

The study involved 9 adult patients with advanced periodontitis and demonstrated that using purified recombinant human platelet-derived growth factor BB (rhPDGF-BB) mixed with bone allograft led to significant periodontal regeneration, including new bone, periodontal ligament, and cementum in both interproximal intrabony defects and Class II furcation lesions.

There were no safety concerns during the study, and the treatment resulted in substantial clinical improvements, with an average clinical attachment level gain of 6.17 mm and a vertical probing depth reduction of 6.42 mm in interproximal defects, indicating effective wound healing and regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. Nevins, M., Camelo, M., Nevins, ML., et al.[2022]

Recombinant human platelet-derived growth factor (rhPDGF-BB) combined with bone graft materials can effectively regenerate periodontal tissue by promoting cellular migration and proliferation, leading to improved healing outcomes.

The use of rhPDGF-BB not only accelerates soft tissue healing at surgical sites but also allows for quicker prosthetic care and earlier resumption of plaque control by patients, enhancing overall recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using recombinant platelet-derived growth factor to facilitate wound healing. Rosen, PS.[2018]

Recombinant platelet-derived growth factor (rPDGF-BB) significantly enhances granulation tissue migration in avascular ulcers, with increases measured at 1.88 mm and 3.00 mm by days 5 and 7, respectively, compared to control treatments.

The combination of rPDGF-BB with a hyaluronic acid carrier and an intact vascular pedicle further boosts tissue generation and is essential for the survival of skin grafts, highlighting the importance of blood supply in effective wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of avascular ulcers with cytokine-induced tissue generation and skin grafting. Brown, DM., Chung, SH., Pasia, EN., et al.[2003]

In a 36-month study involving 135 participants with localized severe periodontal defects, the use of recombinant human platelet-derived growth factor (rhPDGF-BB) significantly improved clinical outcomes, with 87% of patients in the 0.3 mg/mL group achieving a composite success benchmark compared to only 53.8% in the control group.

The study demonstrated that rhPDGF-BB treatment leads to long-term stability in clinical attachment levels and bone growth, indicating its effectiveness in promoting periodontal regeneration over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. Nevins, M., Kao, RT., McGuire, MK., et al.[2022]

Platelet-derived growth factor (PDGF) plays a crucial role in wound healing and bone repair, leading to the FDA approval of recombinant PDGF-BB (rhPDGF-BB) for treating chronic diabetic foot ulcers and periodontal bone defects.

Recent clinical trials suggest that rhPDGF-BB, when combined with beta tricalcium phosphate, may effectively replace autogenous bone grafts in hindfoot and ankle arthrodesis, highlighting its potential in bone regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolution of rhPDGF-BB in musculoskeletal repair and its role in foot and ankle fusion surgery. DiGiovanni, CW., Petricek, JM.[2018]

Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) has been shown to be biocompatible and safe, with no systemic or local toxicity observed in extensive testing, making it a promising option for enhancing wound healing.

The study evaluated the effects of rhPDGF-BB alone and in combination with beta-tricalcium phosphate or collagen, confirming its safety in various applications related to tissue repair and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Toxicology Studies of Recombinant Human Platelet-Derived Growth Factor-BB Either Alone or in Combination with Beta-Tricalcium Phosphate and Type I Collagen. Young, CS., Bradica, G., Hart, CE., et al.[2021]

Recombinant human platelet-derived growth factor-BB (rhPDGF) is safe for use in oral regenerative procedures, with no serious adverse effects reported in 63 studies involving a mean follow-up of 10.7 months.

rhPDGF shows significant clinical benefits when combined with bone allografts, xenografts, or alloplasts for treating periodontal defects and gingival recession, as well as for guided bone regeneration and alveolar ridge preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Human Platelet-Derived Growth Factor: A Systematic Review of Clinical Findings in Oral Regenerative Procedures. Tavelli, L., Ravidà, A., Barootchi, S., et al.[2021]

In a study involving 12 patients with 14 refractory chronic ulcers, 64% of the ulcers healed after treatment with topical rhPDGF gel 0.01%, with an average healing time of 26 weeks.

The treatment was found to be effective and well-tolerated, although 22% of the healed ulcers reopened during a 15-month follow-up, indicating the need for ongoing monitoring after healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human platelet-derived growth factor for refractory nondiabetic ulcers: a retrospective series. Harrison-Balestra, C., Eaglstein, WH., Falabela, AF., et al.[2022]

Recombinant human platelet derived growth factor BB (rhPDGF-BB) expressed in tobacco plants showed a significant increase in fibroblast proliferation (4.5-fold) compared to non-transgenic plants, indicating its potential efficacy in promoting wound healing.

The study confirmed that plant-based production of rhPDGF-BB retains its biological activity, as it not only enhanced cell proliferation but also induced chemotaxis, suggesting therapeutic benefits for treating diabetic neuropathic ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transgenic expression and functional characterization of human platelet derived growth factor BB (hPDGF-BB) in tobacco (Nicotiana tabacum L.). Deepa, K., Rodionov, RN., Weiss, N., et al.[2023]

References

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

Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. [2022]

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

Using recombinant platelet-derived growth factor to facilitate wound healing. [2018]

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

Treatment of avascular ulcers with cytokine-induced tissue generation and skin grafting. [2003]

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

Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. [2022]

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

The evolution of rhPDGF-BB in musculoskeletal repair and its role in foot and ankle fusion surgery. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Preclinical Toxicology Studies of Recombinant Human Platelet-Derived Growth Factor-BB Either Alone or in Combination with Beta-Tricalcium Phosphate and Type I Collagen. [2021]

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

Recombinant Human Platelet-Derived Growth Factor: A Systematic Review of Clinical Findings in Oral Regenerative Procedures. [2021]

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

Recombinant human platelet-derived growth factor for refractory nondiabetic ulcers: a retrospective series. [2022]

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

Transgenic expression and functional characterization of human platelet derived growth factor BB (hPDGF-BB) in tobacco (Nicotiana tabacum L.). [2023]