A Phase 1b, Multicentre, Open Label, Study of the Efficacy, Safety and Tolerability of R131 Ointment in Women with Cytological Abnormalities of the Uterine Cervix
- Conditions
- cervical intraepithelial neoplasia caused by Human papilloma virusCancer - Cervical (cervix)Reproductive Health and Childbirth - Other reproductive health and childbirth disorders
- Registration Number
- ACTRN12618001726246
- Lead Sponsor
- Douglas Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- Female
- Target Recruitment
- 13
1.Provision of written informed consent prior to any study specific procedures;
2.Female participants aged 22-50 years inclusive at the time of screening visit;
3.Positive result for cervical high-risk HPV (types 16, 18 or other);
4.High-grade cytological abnormalities of the uterine cervix defined as HSIL/CIN 2 and above, confirmed by biopsy at Screening, or within 30 days prior to Screening visit,
OR;
low-grade cytological abnormalities of the uterine cervix defined as LSIL/ CIN1 as demonstrated by colposcopic biopsy collected at screening, or within 6 months prior to screening. Only collect biopsy sample if lesion is visible during colposcopic assessment. If no visible lesion, participant should be considered ineligible.
5.Transformation zone needs to be fully visible;
6.Generally, in good health with no clinically significant disease as determined by the investigator;
7.Regular menstrual cycle with an approximate 28-day cycle;
or women who are amenorrhoeic due to effective contraception (such as Mirena, Jadelle, or continuous COC)
8.Agree to abstain from activities such as vaginal douching or insertion of any vaginal products other than the study drug for at least 48 hours prior to enrolment and throughout the study. Tampons or menstrual cups may be used during the participant’s menstrual cycle only.
9.Women of childbearing potential (WOCBP) must use a highly effective form of birth control (confirmed by the Investigator). Rhythm methods will not be considered as highly effective methods of birth control. Highly effective forms of birth control include:
•True sexual abstinence (defined as refraining from heterosexual intercourse for the duration of the study and a minimum of 30 days following the last dose of study drug);
•Vasectomised partner (provided that the partner is the sole sexual partner of the female participant with childbearing potential and that the vasectomised partner has received medical assessment of the surgical success);
•Oral or transdermal combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation;
•Oral, injectable or implantable progestogen-only hormone contraception associated with inhibition of ovulation (Depo-Provera™, Implanon, Cerazette, Noriday (‘mini-pill’);
•Any effective intrauterine device/levonorgestrel intrauterine system;
•Female sterilisation by tubal occlusion;
•Evra Patch™
WOCBP must agree to use a highly effective method of birth control, as defined above, from enrolment, and at least 14 days prior to Day 1, throughout the study duration and within 30 days after the last dose of IMP.
WOCBP are defined as women who are neither permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), nor who are postmenopausal. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months or more without an alternative biological or medical cause e.g. contraceptive method such as Mirena.
10.Male partners of female participants must agree to use condoms during sexual intercourse from the first dose of investigational product until 30 days after the participant’s last dose to avoid potential transfer of investigational product;
11.Able and willing to abstain from sexual intercourse for 6 hours after dosing;
12.Ability and willingness to attend the necessary visits to the clinical trial centre;
13. Ability to comprehend all study related
1.Any significant disease or disorder (e.g. cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the results of the study, or the participant’s ability to participate in the study;
2.Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening and at baseline, which in the opinion of the investigator, may put the participant at risk because of her participation in the study, or may influence the results of the study, or the participant’s ability to complete entire duration of the study;
3.Pregnant, breastfeeding, or lactating women (WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test at the start of each treatment period [i.e. Day 1, Day 28, Day 56]);
4.Women who plan to become pregnant in the next 6 months;
5.History of genital herpes with >3 outbreaks per year, or active non-HPV vaginal infection;
6.Active pelvic infection (positive for gonorrhoea or chlamydial infection, positive test and symptoms for bacterial vaginosis, candida vaginitis or trichomonal vaginitis). Participants with positive results can be treated and re tested once during screening;
7.Positive bimanual exam consistent with pelvic inflammatory disease. Patients may be treated accordingly and re-screened;
8.Positive result for hepatitis B (surface antigen), hepatitis C antibody or human immunodeficiency virus;
9.Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding, within the 3 months prior to Day 1 as assessed by the investigator;
10.Had an abortion or miscarriage or taken the morning-after pill within the 3 months prior to enrolment;
11.Currently taking immunosuppressants, intra-vaginal preparations, or any prescription that in the opinion of the investigator could interfere with the interpretation of the results;
12.Previous exposure to lopinavir/ritonavir (within 3 months prior to screening), contraindication to the use of lopinavir/ritonavir or known allergy, hypersensitivity, or intolerance to any component of lopinavir/ritonavir vaginal ointment excipients;
13.Recent history (within 3 months prior to screening) of Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema, deep vein thrombosis, tinnitus, vertigo, blood glucose disorders, pancreatitis, haemophilia;
14.Receipt of any investigational product within 30 days or 5 half-lives prior to dosing;
15.Employees of the clinical study team or family members (first-degree relatives) of such individuals or anyone involved in the planning and/or conduct of the study. Clinical study team refers to employees directly involved in the study who have been delegated study-related tasks accordingly;
16.Participants who, in the opinion of the Investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method • Changes from baseline to Colposcopic biopsy<br><br>[6 weeks after last dose of R131];• Changes from baseline to the colposcopic appearance of disease[6 weeks after last dose of R131];• Changes from baseline to the presence/absence of HPV genotypes (cervical swab)[6 weeks after last dose of R131]
- Secondary Outcome Measures
Name Time Method • Incidence of adverse events.<br><br>Possible adverse events:<br>Vulvovaginal candidiasis<br>Bacterial vaginosis<br>[6 weeks after last dose of R131];• Changes from baseline in blood pressure (assessed using a blood pressure monitor),[6 weeks after last dose of R131];• Changes from baseline in heart rate (assessed using a blood pressure monitor),[6 weeks after last dose of R131];• Changes from baseline in temperature (assessed using a tympanic thermometer),[6 weeks after last dose of R131];• Changes from baseline in laboratory assessments (haematology).[6 weeks after last dose of R131];• Changes from baseline in safety clinical laboratory assessments (biochemistry).[6 weeks after last dose of R131];• Changes from baseline in: safety clinical laboratory assessments (urinalysis).[6 weeks after last dose of R131]