| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus Type 1 (HIV-1) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003582 |
| E.1.2 | Term | Asymptomatic human immunodeficiency virus type I infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Staff Study Participants (SSP): To evaluate
-acceptability
-appropriateness
-feasibility |
|
| E.2.2 | Secondary objectives of the trial |
Staff Study Participants: To evaluate
-Facilitators to implementation
-Barriers to implementation
-Adaptations/Modifications to address barriers and facilitators
Patient Study Participants (PSP) To evaluate
-Facilitators to implementation
-Barriers to Implementation
To evaluate Patient Study Participants experience of delivering CAB LA + RPV LA, including
-Acceptability
-Appropriateness
-Feasibility
To evaluate sustainability of CAB LA + RPV LA with Study Staff Participants each clinic
To assess fidelity to CAB LA + RPV LA injection dosing windows
Evaluate efficacy and safety measures of CAB LA + RPV LA
To assess preference between CABLA + RPV LA and oral ART medication received prior to entering the study |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A participant will be eligible for inclusion in this study only if all the following criteria are met:
• Be able to understand and comply with protocol requirements, instructions, and
restrictions;
• Understand the long-term commitment to the study and be likely to complete the study as planned;
• Be considered appropriate candidates for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.).
• if he/she meets all eligibility criteria and for whom an individual benefit can be expected.
Source documentation to verify entry criteria must be reviewed by the Principal Investigator or designee prior to enrolment. Source documents from other medical facilities must be located/received during the 35-day screening phase and under no circumstances may the participant be enrolled in the absence of source documentation.
AGE
1. Aged 18 years or older at the time of signing the informed consent.
TYPE OF PARTICIPANT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. HIV-1 infected and must be suppressed on a guideline recommended active HAART regimen for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to
tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for virologic failure (on treatment HIV-1 RNA ≥200 c/mL).
3. Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: at least one < 6 months prior to Screening and one 6-12 months prior to screening;
4. Plasma HIV-1 RNA <50 c/mL at Screening;
SEX
5. A female participant is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test at screen and at Day 1), not lactating, and at least one of the following conditions applies:
a. Non-reproductive potential defined as: Pre-menopausal females with one of the following:
-Documented tubal ligation
-Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
-Hysterectomy
-Documented Bilateral Oophorectomy
-Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment
b. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (Section 10.7) from 30 days prior to the first dose of study medication, throughout the study, and for at least 30 days after discontinuation of all oral study medications and for at least 52 weeks
after discontinuation of CAB LA and RPV LA.
The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.
INFORMED CONSENT
6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians (and next of kin when locally required), must sign a
written Informed Consent Form before any protocol-specified assessments are conducted. Enrolment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct
protocol procedures.
OTHER
7. French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
|
|
| E.4 | Principal exclusion criteria |
HIV-1 RNA
1. Within 6 months prior to Screening, plasma HIV-1 RNA measurement ≥50 c/mL;
2. During the previous 12 months, any confirmed HIV-1 RNA measurement ≥200 c/mL
Exclusionary medical conditions
3. Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study.
4. Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring systemic therapy, and historical or current CD4+ counts <200 cells/mm3are not exclusionary.
5. Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the participant’s ability to comply with the dosing schedule and/or protocol evaluations or which may
compromise the safety of the participant.
6. Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrolment if the Investigator believes
the risk of seizure recurrence is low.
7. Participants who, in the investigator's judgment, pose a significant suicide risk. Participant’s recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk
8. The participant has a tattoo, gluteal implant/ enhancements or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions
9. Evidence of Hepatitis B virus (HBV) infection based on the results of testing forHepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows:
a. Participants positive for HBsAg are excluded;
b. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti HBs (past and/or current evidence) are immune to HBV and are not excluded.
10. Participants who are anticipated to require HCV treatment within 12 months must be excluded. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded; investigators must carefully assess if therapy specific
for HCV infection is required. (HCV treatment on study may be permitted, following consultation and approval of the DAA based therapy being considered with the medical monitor)
11. Participants with HCV co-infection will be allowed entry into this study if:
a. Liver enzymes meet entry criteria
b. HCV Disease has undergone appropriate work-up, and is not advanced.
Additional information (where available) on participants with HCV coinfection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver
disease, prior treatment, and timing/plan for HCV treatment.
c. In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility
i. Fib-4 score >3.25 is exclusionary
ii. Fib-4 scores 1.45 – 3.25 requires Medical Monitor consultation Fibrosis 4 Score
Formula:
(Age x AST) / (Platelets x (sqr [ ALT ])
12. Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of
Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment)
13. History of liver cirrhosis with or without hepatitis viral co-infection.
14. Ongoing or clinically relevant pancreatitis
15. Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty
(PTCA) or any clinically significant cardiac disease.
16. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the
investigator and the Study medical monitor for inclusion of the participant prior to inclusion
17. Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication
18. History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.
A full list of exclusion criteria can be found in the study protocol 5.2 Exclusion Criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Staff Study Participants (SSP):
1)Change of Acceptability of Implementation Measure Score, Implementation Appropriateness Measure Score, Feasibility of Implementation Measure Score over time assessed quantitatively.
2)Semi-structured interviews (SSIs) assessed qualitatively.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Staff Study Participants:
1)Change of Implementation Leadership Scale, Change of Implementation Climate Scale over time assessed quantitatively via questionnaires through Month 12.
2)Summarize components from Enhanced Implementation & Standard Implementation via FRAME-IS outcome Months 2 – 12 (monthly)
3)Summarize components from Enhanced Implementation via CQI 1-hour calls/PDSAs minimum of Months 2-7 (monthly)
4)SSIs assessed qualitatively through Month 12.
5)Total score of the Clinical Sustainability Assessment Tool (CSAT) at Month 12.
Patient Study Participants (PSP)
1)Questionnaires assessed quantitatively through Dose 7.b
2)Length of patient study participant visit from arrival until departure from clinic assessed at Dose 1, Dose 2, Dose 4, and Dose 5.
3)SSIs assessed qualitatively through Dose 7.
4)Change in Acceptability of Intervention Measure Score, Intervention Appropriateness Measure Score, and Feasibility of Intervention Measure Score over time. Assessed via questionnaires at Dose 7. b
5)SSIs assessed qualitatively through Dose 7.
Efficacy Safety and Other Endpoints:
1)Percentage of injections occurring within target window from the target date.
2)Proportion of participants with plasma HIV-1 RNA <50 c/mL over time.
3)Proportion of participants with confirmed virologic failure (CVF) over time
4)Incidence of treatment-emergent genotypic and phenotypic resistance to CAB and RPV in patient study participants with CVF
5)Incidence and severity of AEs, SAEs and proportion of participants who discontinue treatment due to AEs over time
6)Preference between CAB + RPV LA and daily oral ART medication (received prior to entering the study) at quantitatively assessed via preference questionnaire at Dose 7
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Month 12/Dose 7 or otherwise stated |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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