Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201809520959443 Date of Approval: 25/09/2018
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title CAPRISA 018 TAF Implant Trial
Official scientific title A phase I/II trial to assess the safety, acceptability, tolerability and pharmacokinetics of a sustained-release tenofovir alafenamide sub-dermal implant for HIV prevention in women
Brief summary describing the background and objectives of the trial This is a phase I/II trial of a 110mg TAF sub-dermal implant releasing approximately 0.25mg per day. This implant combines two well-established elements; a) TAF, which is a licenced antiretroviral drug widely used in HIV treatment, and b) a sub-dermal implant, which is widely used as a route of administration for contraception. The primary objective of the CAPRISA 018 trial is to evaluate the safety of the sustained-release TAF 120mg sub-dermal implant/s in HIV uninfected young women at low risk for HIV acquisition.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CAPRISA018
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 27/02/2020
Actual trial start date 09/07/2020
Anticipated date of last follow up 31/12/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 550
Actual target sample size (number of participants)
Recruitment status Suspended
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group tenofovir alafenamide TAF 110mg is formulated in a sub-dermal implant, releasing a daily dose of 0.25mg. Maximum of 120 weeks (116 weeks on product and 4 weeks off product) A total of 1, 2, 3 or 4 implants will be inserted, in the inside of the upper arm, to achieve and test the target daily release of 0.25mg, 0.5mg, 0.75mg and 1mg of TAF, respectively. The number of implants, implant location and replacement interval for the phase II component of the trial will be determined from the phase I data. The intervention group will receive the TAF impant plus oral placebo tablets 245
Control Group tenofovir disoproxil fumarate and emtricitabine Oral TDF(300mg)/FTC(200mg) tablets daily plus placebo implant Maximum of 120 weeks (116 weeks on product and 4 weeks off product) the control group will include an active comparator product TDF-FTC 300/200mg oral tablets plus a placebo implant 245 Active-Treatment of Control Group
Experimental Group Tenofovir alafenamide implant 110mg From 28 days (Group 1) to 48 weeks (Group 2 and 3) This Phase I part of the trial assess safety and tolerability with dose escalation, where between 1 to 4 implants will be inserted. The initial safety assessment occurs in six participants (Group 1) followed by a dose escalation component (Groups 2, n=30 and 3, n=24) assessing the safety and PK of TAF 110mg implants releasing a daily dose of 0.25mg (1 implant), 0.5mg (2 implants), 0.75mg (3 implants) and 1mg (4 implants) in healthy, low risk, HIV-negative women. Comparator drugs include TAF 25mg oral tablets and the placebo implant. Once data from Groups 1 to 3 are available, the phase II component (Group 4, n=490) of the trial will be initiated 60
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Female • Age 18-40 years (Phase I participants) • Age 18-30 years (Phase II participants) • Able and willing to provide written informed consent • Able and willing to provide adequate locator information for study retention purposes • HIV-negative on testing performed by study staff • Negative pregnancy test performed by study staff • Agree to use a reliable non-barrier form of contraception during the study and for at least 14 days before enrolment and until 30 days after implant removal (even if not currently sexually active) • In general, be in good health, as assessed clinically • Phase I participants must be at low risk of HIV infection • Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study • Intends relocation from current residential area in the next 12 months • Haemoglobin < 9.5 g/dL • Alanine aminotransferase (ALT) > the upper limit of normal (ULN) • Aspartate aminotransferase (AST) > ULN • Creatinine clearance < 60 mL/min (Cockcroft and Gault estimation) • Hepatitis B surface antigen (HBsAg) positive • LDL or triglycerides or total cholesterol > ULN from a random sample • Past (< 6 months ago) or current participation in any other research study which may interfere with this study • Currently on tenofovir-containing oral PrEP drugs • Currently has a contraceptive implant, only if this would make it difficult to insert the study implant • Has a tattoo or other dermatological condition overlying the inner arm which in the opinion of the Principal Investigator or designee, may interfere with interpretation of insertion site reactions • Bleeding abnormality or on anti-coagulants • Active or planned use of prohibited medications as described in the Study Specific Procudures manual (updated regularly from the OCIS-001 Investigator’s Brochure) • Has any other condition that, based on the opinion of the Principal Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 18 Year(s) 40 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 22/08/2018 University of KwaZulunatals Biomedical research Ethics Committee BREC
Ethics Committee Address
Street address City Postal code Country
Faculty of Health Sciences Ethics Committee Durban 4001 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/06/2018 South African Health Products Regulatory Authority
Ethics Committee Address
Street address City Postal code Country
Private Bag X828 Pretoria 0001 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety as assessed by mean percentage change in creatinine clearance from baseline baseline, week 4, 12, 24, 36, 48, 72, 96 and 120
Secondary Outcome To assess systemic and genital compartment PK of single and multiple TAF 110mg implant/s to determine in-human release rate characteristics, including to compare the PK profiles of insertion of two implants in one arm versus insertion of one implant in each arm. Intensive PK on the day of enrollment and thereafter samples collected at each scheduled visit , depending on Group assigned, until study exit
Secondary Outcome Acceptability - as assesses by participant views on the implant, by summarizing the insertion site reactions, by number of participants who report various insertion site reactions and by summarizing the mean healing time. The same information will be summarized for the placebo arm as the same insertion site reactions are expected as a result of insertion of the placebo implant. Baseline, day 1, week 1, week 4, quarterly thereafter and study exit
Secondary Outcome HIV incidence as assessed by comparing the incidence of HIV in the sustained-release TAF implant (placebo tablet) arm with that in the TDF/FTC (placebo implant) arm baseline, monthly therafter and at study exit
Secondary Outcome HIV viral load When indicated for participants who aquire HIV
Secondary Outcome Frequency of resistance mutations As indicated in participants who acquire HIV
Secondary Outcome Pregnancy rates All visits
Secondary Outcome To assess the incidence of sexually transmitted infections (STIs), including (but not limited to) herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV), gonorrhoea, chlamydia and trichomonas infections. All visits
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
eThekwini Research Clinic 3 Richards Road Durban 4001 South Africa
Vulindlela Research Clinic Road P402, Ward 9, uMgungundlovu district Durban South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Trial Partnership Anna van Saksenlaan 51 The Hague 2593 Netherlands
South African Medical Research Council Francie van Zijl Drive, Parow Valley Cape Town 7500 South Africa
National Research Foundation Meiring Naude Road, Brummeria Pretoria 0001 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Centre for the AIDS Programme of Research in Sauth Africa 719 Umbilo Road Durban 4013 South Africa Non-governmental Research Organisation
COLLABORATORS
Name Street address City Postal code Country
Catherine Hankins Paasheuvelweg 25, Tower C4 Amsterdam 1105 Netherlands
Bruno Pozzetto University-Hospital of Saint-Etienne St.Etienne 3064 France
Marc Baum 132 W. Chestnut Ave California 91016 United States of America
Jaideep A. Gogtay Cipla Limited, Belasis Road Mumbai 400008 India
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Salim Abdool Karim salim.abdoolkarim@caprisa.org +27312604550 719 Umbilo Road, CAPRISA, 2nd Floor DDMRI, Nelson R Mandela School of Medicine, Univeristy of KwaZulu-Natal
City Postal code Country Position/Affiliation
Durban 4013 South Africa Director CAPRISA
Role Name Email Phone Street address
Scientific Enquiries Tanuja Gengiah tanuja.gengiah@caprisa.org +27312604262 719 Umbilo Road, CAPRISA, 2nd Floor DDMRI, Nelson R Mandela School of Medicine, Univeristy of KwaZulu-Natal
City Postal code Country Position/Affiliation
Durban 4013 South Africa Head Pharmacy
Role Name Email Phone Street address
Public Enquiries Smita Maharaj smita.maharaj@caprisa.org +27312604096 719 Umbilo Road, CAPRISA, 2nd Floor DDMRI, Nelson R Mandela School of Medicine, Univeristy of KwaZulu-Natal
City Postal code Country Position/Affiliation
Durban 4013 South Africa Head Media and Communications
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results of the trial will be made publicly available in a timely manner by posting to the results section of the clinical trial registry. In addition, if not already available through a journal website, the datasets on which research papers have been published will be made available to any investigator Informed Consent Form,Statistical Analysis Plan,Study Protocol Within 12 months of study completion To access data, investigators will need to lodge a request on the CAPRISA website (www.caprisa.org). The written request will be assessed by the CAPRISA Scientific Review Committee, and once approved, the dataset will be made available. In line with standard data access principles, CAPRISA will ensure that metadata on the datasets will be made available and anonymization and other measures will be taken to protect individual and personally identifiable information in the datasets.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial phase 16/11/2018 This is a phase I/II study and the study will start with the phase I part and will only proceed to phase II once data from phase I are available Phase-2 Phase-1
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 15/08/2019 Delay in product manufacture 01 Feb 2019 01 Oct 2019
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 03/09/2019 Delay in product manufacture 01 Oct 2019 01 Nov 2019
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 14/12/2019 Delay in manufacturing 01 Nov 2019 27 Feb 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 06/08/2020 Trial open for screening on 9 Jul 2020 09 Jul 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 06/08/2020 First participant enrolled 4 August 2020 Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 27/06/2022 Pending review of PK and safety data Recruiting Suspended
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 25/09/2018 correction Adult: 19 Year-44 Year Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 10/12/2021 Align with protocol Experimental Group, tenofovir alafenamide, TAF 110mg is formulated in a sub-dermal implant, releasing a daily dose of 0.25mg. , Maximum of 120 weeks (116 weeks on product and 4 weeks off product), A total of 1, 2, 3 or 4 implants will be inserted, in the inside of the upper arm, to achieve and test the target daily release of 0.25mg, 0.5mg, 0.75mg and 1mg of TAF, respectively. The number of implants, implant location and replacement interval for the phase II component of the trial will be determined from the phase I data. The intervention group will receive the TAF impant plus oral placebo tablets, 245, Experimental Group, tenofovir alafenamide, TAF 110mg is formulated in a sub-dermal implant, releasing a daily dose of 0.25mg. , Maximum of 120 weeks (116 weeks on product and 4 weeks off product), A total of 1, 2, 3 or 4 implants will be inserted, in the inside of the upper arm, to achieve and test the target daily release of 0.25mg, 0.5mg, 0.75mg and 1mg of TAF, respectively. The number of implants, implant location and replacement interval for the phase II component of the trial will be determined from the phase I data. The intervention group will receive the TAF impant plus oral placebo tablets, 490,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 10/12/2021 Align with protocol Experimental Group, tenofovir alafenamide, TAF 110mg is formulated in a sub-dermal implant, releasing a daily dose of 0.25mg. , Maximum of 120 weeks (116 weeks on product and 4 weeks off product), A total of 1, 2, 3 or 4 implants will be inserted, in the inside of the upper arm, to achieve and test the target daily release of 0.25mg, 0.5mg, 0.75mg and 1mg of TAF, respectively. The number of implants, implant location and replacement interval for the phase II component of the trial will be determined from the phase I data. The intervention group will receive the TAF impant plus oral placebo tablets, 490, Experimental Group, tenofovir alafenamide, TAF 110mg is formulated in a sub-dermal implant, releasing a daily dose of 0.25mg. , Maximum of 120 weeks (116 weeks on product and 4 weeks off product), A total of 1, 2, 3 or 4 implants will be inserted, in the inside of the upper arm, to achieve and test the target daily release of 0.25mg, 0.5mg, 0.75mg and 1mg of TAF, respectively. The number of implants, implant location and replacement interval for the phase II component of the trial will be determined from the phase I data. The intervention group will receive the TAF impant plus oral placebo tablets, 245,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 10/12/2021 Aligned with protocol Experimental Group, Tenofovir alafenamide implant , 110mg, From 28 days (Group 1) to 48 weeks (Group 2 and 3), This Phase I part of the trial assess safety and tolerability with dose escalation, where between 1 to 4 implants will be inserted. The initial safety assessment occurs in six participants (Group 1) followed by a dose escalation component (Groups 2, n=30 and 3, n=24) assessing the safety and PK of TAF 110mg implants releasing a daily dose of 0.25mg (1 implant), 0.5mg (2 implants), 0.75mg (3 implants) and 1mg (4 implants) in healthy, low risk, HIV-negative women. Comparator drugs include TAF 25mg oral tablets and the placebo implant. Once data from Groups 1 to 3 are available, the phase II component (Group 4, n=490) of the trial will be initiated, 60,
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 10/12/2021 Aligned with study protocol Secondary Outcome, non-compartmental PK model, Daily for first 7 days post insertion then weekly thereafter until week 8 Secondary Outcome, To assess systemic and genital compartment PK of single and multiple TAF 110mg implant/s to determine in-human release rate characteristics, including to compare the PK profiles of insertion of two implants in one arm versus insertion of one implant in each arm. , Intensive PK on the day of enrollment and thereafter samples collected at each scheduled visit , depending on Group assigned, until study exit
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 10/12/2021 Aligned with protocol Secondary Outcome, To assess the incidence of sexually transmitted infections (STIs), including (but not limited to) herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV), gonorrhoea, chlamydia and trichomonas infections. , All visits