Impact of AV2 Antiviral Drug on the Treatment of HPV-associated Lesions of the Uterine Cervix

NCT02346227 | Completed Phase 3 DMC

• 1 other identifier: UA-IHU- 2012-01
• Study Type: interventional
• Target: 327
• Locations: 1 country
• Sites: 1

Brief Summary

• Evaluate the clinical efficacy of AV2 as a treatment for HPV-associated lesions of the uterine cervix;
• Identify HPV genotypes found in Kinshasa;
• Determine the cost-effectiveness of an algorithm combining screening by VIA and AV2 and that combining VIA and cryotherapy treatment;
• Methods After basic training of local health workers on VIA, on collection of cervical samples for HPV testing (quantitative Polymerase Chain reaction, qPCR) and liquid-based cytology (LBC) and on application of AV2, a screening and treatment program will be offered to women aged 25 and older who will give their informed consent.

Conditions

Uterine Cervical Dysplasia; Papillomavirus Infections

Keywords

Human Papillomavirus; Uterine cervix; Infection; Antiviral Drug; Therapeutic use

Outcome Measures

Primary Outcomes (1)

• Change of lesions

  lesion size" on a scale of 0 - 1 - 2: 0 : for a lesion \< 5 mm 1. : for a lesion 5-15 mm or involving 2 quadrants of the cervix 2. : for a lesion \> 15 mm or involving 3-4 quadrants or endocervically undefined.

  2 months

Secondary Outcomes (3)

• absence of HPV DNA

  2 months

• correlation between change of lesions and change in HPV DNA

  2 months

• Change in HPV viral particle load

  6 months

Other Outcomes (1)

• number of patients with adverse effects

  2 months

Study Arms (2)

AV2

ACTIVE COMPARATOR

Drug: application of topical spray on the cervix one time (2 puffs) topical application of 100µl AV2 antiviral spray( natural essential oil components in equal volumes diluted 50% in olive oil)

Drug: AV2

Placebo

PLACEBO COMPARATOR

Drug: application of topical spray on the cervix one time (2 puffs) topical spray of 100 µl on the cervix.

Drug: Placebo

Interventions

AV2 DRUG

The virucide AV2 consists of a spray. It is a mixture of natural essential oil components (Carvone, Eugenol, Geraniol, Nerolidol) in equal volumes diluted 50% in olive oil (Olea europaea). It is administered as a topical spray to the cervix while the subject is in the lithotomic position and fitted with a speculum. The manual spray applicator is positioned inside the anterior of the vagina and two pumps are applied. Each pump delivers 100 microliters of the solution.

Also known as: Antivirus 2

AV2

Placebo DRUG

The placebo consists of 10% lemon (citrus limon) and 10% lime (citrus aurantifolia) in 80% olive oil. It is administered as a one time (2 puffs) topical spray of 100 microliters on the cervix.

Also known as: lemon, lime & olive oil.

Placebo

Eligibility Criteria

• Age: 25 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sexually-active women
• Women with intact uterine cervix
• Voluntary written informed consent to participate in the study

You may not qualify if:

• Virgin women
• Pregnant or breast-feeding women, and women in the post-partum period
• Subject is already diagnosed with cervical cancer
• Medical history of any severe diseases like hepatitis, renal or liver dysfunction, cardiovascular, gastrointestinal, malignant tumor, or psychiatric disorders etc., which might influence the assessments or conduct of the trial by the discretion of the investigator
• Intake or application of antivirals or other prohibited concomitant medication within 30 days prior to application of AV2®, or patients who plan to take such drugs during the trial
• Known or suspected allergic or adverse response to the investigational product AV2 or its components (olive oil or d-limonene)
• Inability to follow the study protocol

Sponsors & Collaborators

• Jean-Pierre Van geertruyden: lead
• University of Kinshasa: collaborator
• University Hospital, Antwerp: collaborator

Study Sites (1)

Centre de Santé Lisungi

Kinshasa, Mont-Ngafula, Route Kimwenza n°23, Democratic Republic of the Congo

Location

Related Publications (7)

• Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

  PMID: 21351269 BACKGROUND

• Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnurch HG, zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci U S A. 1983 Jan;80(2):560-3. doi: 10.1073/pnas.80.2.560.

  PMID: 6300854 BACKGROUND

• Sankaranarayanan R, Chatterji R, Shastri SS, Wesley RS, Basu P, Mahe C, Muwonge R, Seigneurin D, Somanathan T, Roy C, Kelkar R, Chinoy R, Dinshaw K, Mandal R, Amin G, Goswami S, Pal S, Patil S, Dhakad N, Frappart L, Fontaniere B. Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: results from a multicenter study in India. Int J Cancer. 2004 Nov 1;112(2):341-7. doi: 10.1002/ijc.20396.

  PMID: 15352050 BACKGROUND

• Sarian LO, Derchain SF, Naud P, Roteli-Martins C, Longatto-Filho A, Tatti S, Branca M, Erzen M, Serpa-Hammes L, Matos J, Gontijo R, Braganca JF, Lima TP, Maeda MY, Lorincz A, Dores GB, Costa S, Syrjanen S, Syrjanen K. Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America. This report refers to partial results from the LAMS (Latin AMerican Screening) study. J Med Screen. 2005;12(3):142-9. doi: 10.1258/0969141054855328.

  PMID: 16156945 BACKGROUND

• World Health Organization. HPV Summary Report 2010

  BACKGROUND

• Baleka Mutombo A, Tozin R, Kanyiki H, Van Geertruyden JP, Jacquemyn Y. Impact of antiviral AV2 in the topical treatment of HPV-associated lesions of the cervix: Results of a phase III randomized placebo-controlled trial. Contemp Clin Trials Commun. 2019 May 16;15:100377. doi: 10.1016/j.conctc.2019.100377. eCollection 2019 Sep.

  PMID: 31193477 DERIVED

• Mutombo AB, Tozin R, Simoens C, Lisbeth R, Bogers J, Van Geertruyden JP, Jacquemyn Y. Efficacy of antiviral drug AV2 in the treatment of human papillomavirus-associated precancerous lesions of the uterine cervix: A randomized placebo-controlled clinical trial in Kinshasa, DR Congo. (KINVAV study). Contemp Clin Trials Commun. 2017 Sep 28;8:135-139. doi: 10.1016/j.conctc.2017.09.008. eCollection 2017 Dec.

  PMID: 29696202 DERIVED

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Papillomavirus Infections; Infections

Interventions

lime; Olive Oil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Yves Jacquemyn, MD PhD

  University Hospital, Antwerp

  STUDY DIRECTOR

• Alex Mutombo Baleka, MD

  University of Kinshasa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: November 8, 2014
• First Posted: January 26, 2015
• Study Start: January 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 12, 2018

Record last verified: 2018-10

Locations

DE (1)