Penile Transplant for Traumatic Amputation

Overseen By TBD TBD

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Johns Hopkins University

Must be taking: Tacrolimus

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of penile transplantation, using a special treatment plan, to assist individuals who have lost most of their penis due to injury or cancer. The goal is to determine if this approach can restore normal appearance and function more effectively than traditional surgeries. The trial is open to men who have experienced significant penile loss or have severe congenital issues and are committed to following the treatment plan.

As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval. Participants have the opportunity to contribute to groundbreaking advancements in penile reconstruction.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since the study involves an immunomodulatory protocol, it's possible that adjustments to your medications might be necessary. It's best to discuss this with the study team.

What prior data suggests that penile transplantation is safe?

Research has shown that penile transplants are generally safe for patients. In a review of five transplants, four yielded good results, indicating most patients fared well post-surgery. However, these transplants are complex and involve major surgery.

Tacrolimus, a drug used to prevent transplant rejection, has demonstrated safety in studies of other transplants over two years. This drug is commonly used in transplants, suggesting it is relatively safe for this purpose.

Monoclonal antibodies are also part of this treatment. These lab-made proteins help the body address specific issues, such as transplant rejection. Although information about their safety is limited, they are widely used in modern treatments.

Overall, while these treatments have shown positive safety results, the complexity and risks of such advanced procedures must be considered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about penile transplantation for traumatic amputation because it offers a groundbreaking approach that goes beyond traditional reconstructive surgery. Unlike standard procedures, which primarily involve prosthetics or local tissue reconstruction, this treatment uses a combination of monoclonal antibody induction therapy and donor bone marrow infusion. This innovative protocol aims to improve graft acceptance and reduce the risk of rejection using tacrolimus monotherapy. By potentially restoring both form and function in a way that other methods cannot, this treatment represents a significant leap forward in regenerative medicine for those affected by penile loss.

What evidence suggests that penile allotransplantation could be an effective treatment for traumatic amputation?

Research has shown that penile allotransplantation, a type of organ transplant, offers promising results for restoring function after genital loss. Past cases indicate that patients experienced good urinary flow, improved erectile function, and regained sensation within months of the procedure. In this trial, participants will undergo penile transplantation with an immunomodulatory protocol, which includes monoclonal antibody induction therapy and tacrolimus monotherapy, to help the body accept the transplant. Studies suggest this method may offer better results than traditional surgeries by replacing the lost organ with a similar one. Although still developing, this technique has shown encouraging results in restoring both the appearance and function of the penis more effectively than older methods. ^{6 7 8 9 10}

Who Is on the Research Team?

Richard Redett, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for males aged 18-69 who have lost most of their penis due to injury or cancer. Donors must be brain-dead, a blood type match, stable without strong drugs to maintain blood pressure, and with family consent. Recipients should closely match the donor's skin tone.

Inclusion Criteria

My donor's blood pressure is stable without needing a lot of medication.

Donor: Brain dead meeting the criteria for Determination of Death

Donor: Family consent for penile graft donation

Exclusion Criteria

I have active tuberculosis.

I have a genetic condition that affects my nerves.

I was diagnosed with cancer within the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Penile transplantation with an immunomodulatory protocol consisting of monoclonal antibody induction therapy followed by donor bone marrow infusion and tacrolimus monotherapy

Immediate post-operative period

Follow-up

Participants are monitored for allograft survival and functional return with reduced dosing/frequency of maintenance immunosuppression

5 years

Long-term Follow-up

Assessment of quality of life and psychosexual measures using various questionnaires

12-60 months post-transplant

What Are the Treatments Tested in This Trial?

Interventions

• Monoclonal Antibody
• Penile Allotransplantation
• Tacrolimus

Trial Overview The study tests penile allotransplantation using immunosuppression (tacrolimus) and humanized anti-CD52 antibodies. It aims to achieve graft survival with reduced immunosuppression and compare outcomes with traditional reconstructions in terms of function and quality of life.

How Is the Trial Designed?

Group I: Treatment: Transplantation Experimental Treatment 3 Interventions

Penile transplantation with an immunomodulatory protocol consisting of monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Long-term outcomes of penis transplants have been promising, particularly with proper compliance to immunosuppressive therapy, showing stable leukocyte counts and renal function up to 3 years post-transplant.

Continuous nerve regeneration in penile allografts has been observed for up to 3 years, indicating potential for functional recovery, although ethical and psychosocial considerations remain important for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons learned from the first 15 years of penile transplantation and updates to the Baltimore Criteria. Lopez, CD., Girard, AO., Lake, IV., et al.[2023]

Penile transplantation is a complex surgical procedure that has been successfully performed in three cases, with one patient achieving natural erections and the ability to impregnate his partner, demonstrating its potential for functional restoration.

Despite its success, the procedure poses significant ethical and psychosocial challenges, and there is still uncertainty regarding the effects of rejection and immunosuppression on graft function, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penile Allotransplantation for Complex Genitourinary Reconstruction. Sopko, NA., Tuffaha, SH., Lough, D., et al.[2022]

Penile transplantation has shown promise in restoring urinary function, natural erections, and sensation, but it is not yet considered standard care, and long-term outcomes remain uncertain.

The study proposes the Baltimore Criteria for an Ethical Approach to Penile Transplantation, emphasizing the need for clear guidelines and ethical considerations in this emerging field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Baltimore Criteria for an ethical approach to penile transplantation: a clinical guideline. Ngaage, LM., Elegbede, A., Sugarman, J., et al.[2021]

Penile transplantation, a complex surgical procedure involving vascularized composite allotransplantation, has been successfully performed in five cases worldwide, indicating its feasibility as a treatment option.

The procedure raises important ethical considerations regarding its aesthetic outcomes, potential complications, functional results, and cost compared to the less invasive alternative of phalloplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Penile Transplantation: An Unjustified Ethical Dilemma? Patel, HD.[2022]

A novel ex vivo model demonstrated that rejection of penile tissue due to allogenic PBMC activation leads to impaired cavernous tissue physiology, characterized by cellular infiltration and apoptosis.

Cyclosporine A (CsA) effectively prevented rejection but did not enhance tissue relaxation, suggesting that other immunosuppressants like FK506 may be more beneficial for maintaining erectile function in penile transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology. Sopko, NA., Matsui, H., Lough, DM., et al.[2022]

Penile transplantation is being explored as a promising solution for patients with severe genital defects, particularly in cases of male genitourinary trauma, which is increasingly common in military settings.

The article highlights the limitations of traditional reconstructive methods and emphasizes the need for careful consideration of technical, logistical, and ethical factors to ensure successful outcomes in penile transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penile transplantation: an emerging option for genitourinary reconstruction. Tuffaha, SH., Cooney, DS., Sopko, NA., et al.[2022]

The first successful penis transplant in the U.S. was performed on a patient who had undergone subtotal penectomy due to penile cancer, demonstrating the feasibility of this procedure for restoring anatomy and function.

Despite experiencing some complications, including rejection that required treatment, the patient reported significant improvements in self-image and health satisfaction, indicating the potential psychological benefits of penile transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penis Transplantation: First US Experience. Cetrulo, CL., Li, K., Salinas, HM., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02395497

NCT02395497 | Human Penile Allotransplantation The investigators propose this clinical trial to determine functional outcomes and quality of life for Wounded Warriors and civilians who choose to undergo ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6127561/

Penile transplantation: the US experience and institutional ... Penile transplantation using vascularized composite allografts is an emerging technique to treat genital loss.

3. auajournals.org auajournals.org/doi/10.1097/JU.0000000000002504

Penile Transplantation: Lessons Learned and Technical ... Five penile transplant cases have been reported in literature, 4 with published methodology and outcomes data. All 4 detailed unique surgical ...

4. cureus.com cureus.com/articles/317017-experimental-models-in-penile-transplantation-translational-insights-and-relevance-to-clinical-application

Experimental Models in Penile Transplantation Subsequently, the patient reported a good urinary stream, erectile function, and sensation at the penile shaft 6 months after the procedure. The ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06781606

NCT06781606 | Pilot Study of PEnile TRAnsplantation Penile transplantation (PT) has recently emerged as an option for penile reconstruction and has shown encouraging outcomes at the international level with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11854063/

PMC Search Update - PubMed Central This review provides evidence-based recommendations on current and emerging immunotherapy and monoclonal antibody treatments for male reproductive cancers

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03240822

Human Penile Tissue Allotransplantation for Devastating ... Outcomes will include but not be limited to functional metrics (sensation, erection, voiding), psychosocial (body integrity, adaptation to transplant) and ...

8. journalwjbphs.com journalwjbphs.com/sites/default/files/fulltext_pdf/WJBPHS-2025-0672.pdf

Immunomodulatory therapies to prevent transplant rejection in ... The pinnacle will be the development of immune tolerance, which may make CTA immunosuppression-free. This review compares clinical outcomes, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0022356524171236

First-in-Human Phase 1 Randomized Trial with the Anti ... This first-in-human, randomized, double-blind, placebo-controlled study (NCT04497662) evaluated safety, pharmacokinetics, receptor occupancy, and ...

10. nature.com nature.com/articles/s41585-022-00617-x

Immune-based therapies in penile cancer Current evidence regarding the safety and efficacy of immune-based therapies is limited in penile cancer, but a number of clinical and ...