A Clinical Trial to Investigate the Safety and Efficacy of Papillex® on Abnormal Cervical Cells Caused by HPV.

A Randomized, Triple-blind, Placebo-controlled, Parallel Clinical Trial to Investigate the Safety and Efficacy of Papillex® on Abnormal Cervical Cells Caused by HPV

The goal of this clinical trial is to investigate the safety and efficacy of Papillex® on the regression of abnormal cervical cells caused by HPV in women with a cervical intraepithelial neoplasia (CIN) 1 or 2 diagnosis. The main question it aims to answer is:

Is there a difference in the proportion of participants with a regression in CIN based on histology or cytology from baseline at day 180 between Papillex® and placebo?

Participants will be asked to consume Papillex® or placebo for 180 days, complete questionnaires, a PAP smear, HPV test, and colonoscopy (where applicable).

Study Overview

• Status: Recruiting
• Conditions: HPV; CIN - Cervical Intraepithelial Neoplasia; CIN 2; CIN 1; Cervical Cells
• Intervention / Treatment: Dietary supplement: Papillex®; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Erin Lewis, PhD; Phone Number: 248 1-226-242-4551; Email: elewis@kgkscience.com

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N5Y 5V6
      • Recruiting
      • KGK Science Inc.
      • Contact: Erin Lewis, PhD; Phone Number: 248 1-226-242-4551; Email: elewis@kgkscience.com
      • Principal Investigator: David Crowley, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Females between 25 and 55 years of age

2. Females not of child-bearing potential, defined as those who have undergone a permanent sterilization procedure (e.g. hysterectomy, bilateral oophorectomy or bilateral tubal occlusion) or have been post-menopausal for at least 1 year prior to screening Or,

   Individuals of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

   • Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), hormone implant (Norplant System) or intrauterine hormone-releasing system
   • Double-barrier method
   • Intrauterine devices
   • Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
   • Vasectomized partner, provided that partner is the sole sexual partner and that the vasectomised partner has received medical assessment of the surgical success
   • Abstinence
3. Histologically confirmed CIN1+ (as per standard of care) with concordant hrHPV positivity at that time, and current abnormal cytology and hrHPV positivity at screening; interval between historical diagnosis and screening must be >12 months OR documented abnormal cytology (LSIL or worse) plus hrHPV positive >12 months prior, and current abnormal cytology with hrHPV positivity at screening
4. Willing to provide copies of histology and/or cytology reports for eligibility confirmation
5. Agrees to maintain current lifestyle habits (diet, physical activity, medications, supplements, and sleep) as much as possible throughout the study
6. Willingness to avoid magnetic resonance imaging, computed tomography, X-ray, or other procedures with contrast media injection for 48 hr prior to study visits assessing micronutrient status
7. Willingness and ability to complete questionnaires and diaries associated with the study, and to complete all clinic visits and assessments
8. Provided voluntary, written, informed consent to participate in the study
9. Otherwise healthy as determined by medical history and laboratory results as assessed by Qualified Investigator (QI)

Exclusion Criteria:

1. Women who are pregnant, breast feeding, or planning to become pregnant during the study
2. Allergy, sensitivity, or intolerance preventing consumption of investigational product or placebo ingredients
3. Currently undergoing treatment for CIN, are indicated for treatment during the study period, have received treatment (e.g., conization or loop electrosurgical excision procedure) within the last five years, or have active CIN 3
4. Concurrent uterine pathologies
5. History of hysterectomy or destructive therapy of the cervix
6. Cervical cancer
7. Unstable metabolic disease or chronic diseases as assessed by the QI
8. Current or history of any significant diseases of the gastrointestinal tract as assessed by the QI
9. Unstable hypertension. Treatment on a stable dose of medication for at least 3 months will be considered by the QI (See Section 7.3)
10. Significant cardiovascular event in the past 6 months. Participants with no significant cardiovascular event on stable medication may be included after assessment by the QI on a case-by-case basis
11. History of or current diagnosis with kidney and/or liver diseases as assessed by the QI on a case-by-case basis, with the exception of history of kidney stones in participants who are symptom free for 6 months
12. Self-reported confirmation of current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI
13. Major surgery in the past 3 months or individuals who have planned surgery during the course of the study. Participants with minor surgery will be considered on a case-by-case basis by the QI
14. Cancer, except skin basal cell carcinoma completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable
15. Individuals with an autoimmune disease or are immune compromised
16. Self-reported confirmation of a HIV-, Hepatitis B- and/or C-positive diagnosis as assessed by the QI
17. Self-reported confirmation of blood/bleeding disorders as assessed by the QI
18. Alcohol intake average of >2 standard drinks per day as assessed by the QI
19. Alcohol or drug abuse within the last 12 months
20. Current use of prescribed and/or over-the-counter (OTC) medications, supplements, and/or consumption of food/drinks that may impact the efficacy and/or safety of the investigational product (Section 7.3)
21. Clinically significant abnormal laboratory results at screening as assessed by the QI
22. Blood donation 30 days prior to baseline, during the study, or a planned donation within 30 days of the last study visit
23. Participation in other clinical research studies 30 days prior to baseline, as assessed by the QI
24. Individuals who are cognitively impaired and/or who are unable to give informed consent
25. Any other condition or lifestyle factor, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Other: Placebo; Participants will be instructed to take two capsules twice daily with food, with the first dose taken with the first meal of the day and the second dose taken with the last meal of the day.
Experimental: Papillex®; The investigational product, Papillex®, is a dietary supplement containing vitamins B12, C, and E, mixed carotenoids, folate, zinc, selenium, green tea leaf extract, broccoli sprout powder, astragalus, natural all-trans-lycopene and reishi mushroom extracts	Dietary supplement: Papillex®; Participants will be instructed to take two capsules twice daily with food, with the first dose taken with the first meal of the day and the second dose taken with the last meal of the day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in the proportion of participants with cytology improvement	The difference in the proportion of participants with cytology improvement defined as improvement by ≥1 Bethesda category on Pap smear (e.g., HSIL→LSIL/NILM; LSIL→NILM) from baseline at day 180 between Papillex® and placebo.	Day 0 to 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in the proportion of participants with cytology improvement	The difference in the proportion of participants with cytology improvement defined as improvement by ≥1 Bethesda category on Pap smear (e.g., HSIL→LSIL/NILM; LSIL→NILM) from baseline at day 360 between Papillex® and placebo.	Day 0 to 360
The difference in the proportion of participants with genotype-specific HPV clearance,	The difference in the proportion of participants with genotype-specific HPV clearance, defined as negative for the genotypes present at baseline, at day 360 between Papillex® and placebo	Day 0 to 360
Change in immune markers (T lymphocytes, interferon (IFN)-β) between Papillex® and placebo	Change in immune markers (T lymphocytes, interferon (IFN)-β) from baseline to day 180 between Papillex® and placebo	Day 0 to 180
The difference in the proportion of responders	The difference in the proportion of responders, defined as cytology improvement at day 180 OR genotype-specific HPV clearance at day 360	Day 0 to 180, or 360
The difference in the proportion of deep responders	The difference in the proportion of deep responders, defined as cytology improvement at day 180 AND genotype specific HPV clearance at day 360, between Papillex® and placebo	Day 0 to 180 and 360
Concordance between cytology and histology results (where performed as standard of care)*	Concordance between cytology and histology results (where performed as standard of care)*. *For participants who elect to provide colposcopy reports at screening/baseline and during/following completion of the clinical trial (minimum of n = 20; n = 10/group)	Day 0 to 360
Change in micronutrient status	Change in micronutrient status from baseline to day 180 between Papillex and placebo as assessed by blood concentrations of vitamin B12, folate (vitamin B9), zinc, and selenium.	Day 0 to 180
Change in Symptoms Checklist score between Papillex® and placebo	Change in Symptoms Checklist score from baseline to days 180 between Papillex® and placebo	Day 0 to 180
Change in Symptoms Checklist score between Papillex® and placebo	Change in Symptoms Checklist score from baseline to days 360 between Papillex® and placebo	Day 0 to 360
Change in SF-36 Quality of Life (QoL) score between Papillex® and placebo	Change in SF-36 Quality of Life (QoL) score from baseline to days 180 between Papillex® and placebo	Day 0 to 180
Change in SF-36 Quality of Life (QoL) score between Papillex® and placebo	Change in SF-36 Quality of Life (QoL) score from baseline to days 360 between Papillex® and placebo	Day 0 to 360
Incidence of post-emergent adverse events (AE)	Incidence of post-emergent adverse events (AE)	Day 0 to 360

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant changes in blood pressure after supplementation	Clinically relevant changes in blood pressure after supplementation at Day 180	Day 0 to 180
Clinically relevant changes in heart rate after supplementation	Clinically relevant changes in heart rate after supplementation at Day 180	Day 0 to 180
Clinically relevant changes in complete blood count after supplementation at Day 180		Day 0 to 180
Clinically relevant changes in clinical chemistry after supplementation at Day 180		From enrollment to Day 180

Collaborators and Investigators

• Sponsor: Papillex Inc.
• Investigators: Principal Investigator: David Crowley, MD, KGK Science Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 12, 2025
• First Submitted That Met QC Criteria: May 12, 2025
• First Posted (Actual): May 18, 2025

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HPV; Cervical intraepithelial neoplasia; Papillex
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Precancerous Conditions; Uterine Cervical Diseases; Uterine Cervical Dysplasia
• Other Study ID Numbers: 24PXCFP01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No