Gardasil Versus Cervarix in the Treatment of Warts

Quadrivalent and Bivalent Human Papilloma Virus Vaccines in the Treatment of Common Recalcitrant Warts

Warts are common, benign, epidermal proliferations caused by HPV infecting skin and mucous membranes. Treatment of warts poses a true challenge despite existing variable therapeutic modalities, whether destructive or immunotherapeutic. Human papilloma virus (HPV) vaccines are FDA approved for the prevention of genital warts and wart related precancerous and cancerous lesions but they are not indicated for treatment of preexisting warts yet

Study Overview

• Status: Completed
• Conditions: Verruca Viral
• Intervention / Treatment: Drug: Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recombinant Vaccine; Drug: Bivalent Human Papilloma Virus Vaccine; Drug: Saline

Detailed Description

Approximately 35% of viral warts tend to be recalcitrant either showing no response to treatment or having prompt recurrences after treatment, causing frustration for both patients and physicians. Success rates vary significantly across patients and across different therapeutic interventions ranging from 7% to 90%.

Immunotherapy is proposed to enhance virus recognition by the cell mediated immunity, which allows the clearance of both treated and untreated warts and helps to prevent recurrences through induction of a long-term acquired immunity to HPV.

Few reports suggest the possibility of using quadrivalent or bivalent HPV vaccines as therapeutic modality rather than only preventive modality. This is a randomized controlled study to assess the efficacy and safety of quadrivalent and bivalent HPV vaccines in the treatment of warts

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Select Region
    • Zagazig, Select Region, Egypt, 44511
      • Dermatology department, Zagazig University Hospitals, Faculty of Medicine, Zagazig University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult Patients with recalcitrant multiple warts of any type. Warts were considered recalcitrant if they persisted for at least 6 months without any response to 2 different therapeutic modalities or more.
• Immunocompetent patients.

• Patients who do not receive any treatment of warts for at least 1 month before the start of study.

  • Patients who are able to understand and follow the study protocol and approve to sign the informed consent

Exclusion Criteria:

• Patients with acute febrile illness.
• Past history of asthma.
• Allergic skin disorders, such as generalized eczema, or severe urticaria.

• Pregnancy or lactation

  • History of hypersensitivity to the treatment vaccines.
  • Children
  • Immunocompromised patients
  • Patients unable to follow the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quadrivalent vaccine; Patient receive 0.1 ml of quadrivalent HPV vaccine intralesional every two weeks	Drug: Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recombinant Vaccine; intralesional 0.1 ml every two weeks
Experimental: Bivalent Vaccine; Patient received 0.1 ml of bivalent HPV vaccine intralesional once every two weeks	Drug: Bivalent Human Papilloma Virus Vaccine; Intralesional 0.1 ml every two weeks
Placebo Comparator: Saline control; Patient received 0.1 ml of intralesional saline once every two weeks	Drug: Saline; intralesional into the largest warts every two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic response	The percentage of patients in each group achieving complete, partial or no response at the end of the treatment sessions	Through study completion for a maximum of 12 weeks, evaluation held at two weeks interval and at the end of treatment sessions (12th week visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety measure	Immediate adverse events recorded by the treating physician within 1 hour post injection	Through study completion every treatment session held at two weeks interval for a maximum of 5 sessions
Safety measure	Delayed adverse events reported by the patients in between sessions	Through study completion for a maximum of 12 weeks held every two weeks till the end of the treatment sessions (12th week visit)
Recurrence	Percentage of patients experiencing recurrences in each group	6 months following the end of treatment sessions

Collaborators and Investigators

• Sponsor: Zagazig University

Publications and helpful links

General Publications

• Nofal A, Marei A, Ibrahim AM, Nofal E, Nabil M. Intralesional versus intramuscular bivalent human papillomavirus vaccine in the treatment of recalcitrant common warts. J Am Acad Dermatol. 2020 Jan;82(1):94-100. doi: 10.1016/j.jaad.2019.07.070. Epub 2019 Jul 29.
• Nofal A, Marei A, Amer A, Amen H. Significance of interferon gamma in the prediction of successful therapy of common warts by intralesional injection of Candida antigen. Int J Dermatol. 2017 Oct;56(10):1003-1009. doi: 10.1111/ijd.13709. Epub 2017 Aug 8.
• Nofal A, Nofal E, Yosef A, Nofal H. Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: a promising approach. Int J Dermatol. 2015 Jun;54(6):667-71. doi: 10.1111/ijd.12480. Epub 2014 Jul 29.
• Landis MN, Lookingbill DP, Sluzevich JC. Recalcitrant plantar warts treated with recombinant quadrivalent human papillomavirus vaccine. J Am Acad Dermatol. 2012 Aug;67(2):e73-4. doi: 10.1016/j.jaad.2011.08.022. No abstract available.
• Kreuter A, Waterboer T, Wieland U. Regression of cutaneous warts in a patient with WILD syndrome following recombinant quadrivalent human papillomavirus vaccination. Arch Dermatol. 2010 Oct;146(10):1196-7. doi: 10.1001/archdermatol.2010.290. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; DNA Virus Infections; Skin Diseases, Infectious; Papillomavirus Infections; Skin Diseases, Viral; Tumor Virus Infections; Warts; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: ZU-IRB#5859/15-1-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes