| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus Type-1 (HIV-1) |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 |
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| 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 |
| To demonstrate the non-inferior antiviral activity of CAB LA + RPV LA every two months compared to a BIK single tablet regimen administered once daily over 12 months in suppressed HIV-1 infected antiretroviral therapy (ART)-experienced participants |
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| E.2.2 | Secondary objectives of the trial |
To demonstrate the antiviral and immunologic activity of CAB LA + RPV LA every 2 months compared to a BIK single tablet regimen administered once daily.
To assess viral resistance in participants experiencing protocol-defined confirmed virologic failure.
To evaluate renal (in urine and blood) and bone (in blood) biomarkers in participants treated with CAB LA + RPV LA compared to BIK.
To evaluate Metabolic Syndrome for participants treated with CAB + RPV and BIK.
To evaluate insulin resistance in participants treated with CAB LA + RPV LA compared to BIK.
To assess preference for CAB LA + RPV LA administered every 2 months compared to a BIK single tablet regimen administered once daily.
To assess patient reported treatment satisfaction, and injection tolerability.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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 .
Aged 18 years or older (or ≥19 where required by local regulatory agencies), at the time of signing the informed consent.
A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at screen and a negative urine hCG test at Randomization), 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) from 30 days prior to the first dose of study medication, throughout the study, 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 properly use these methods of contraception.
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.
Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
Must be on the uninterrupted current regimen of BIK for at least 6 months prior to Screening with an undetectable HIV-1 viral load for at least 6 months prior to Screening. Only a single prior INI regimen is allowed if BIK is a second line regimen 6 months prior to screening. Any prior change in regimen, 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 treatment failure (HIV-1 RNA ≥400 c/mL).
Only a single prior INI regimen is permitted with the following limited exceptions:
•A change from TDF to TAF will not be considered a regimen change.
•Historical perinatal use of an NRTI when given in addition to an ongoing HAART will not be considered a change in ART regimen.
•The past use of ARVs in the context of PEP or PrEP while the patient was HIV negative will be allowed. Such cases will be evaluated on a case by case basis and may require documentation of HIV negative serology during time of PEP or PrEP
•A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy.
A change in formulation from multiple class regimens to single treatment regimens (of the same medications) would not be considered a change in ART regimen.
Documented evidence of plasma HIV-1 RNA measurements <50 c/mL in the 6 months prior to Screening.
Plasma HIV-1 RNA <50 c/mL at Screening.
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| E.4 | Principal exclusion criteria |
Within 6 months prior to Screening, any plasma HIV-1 RNA measurement ≥50 c/mL.
Within the 6 to 12-month window prior to Screening, any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 RNA measurements ≥50 c/mL. NOTE: This statement does not apply to study participants who started treatment within the 6 to 12-month window prior to screening.
History of prior treatment failure to any DHHS recommended ART regimen.
History of drug holiday >1 month for any reason prior to Screening visit, except where all ART was stopped due to tolerability and/or safety concerns.
Any change to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement ≥200 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen).
Participants who are currently participating in or anticipate being selected for any other interventional study.
Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
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 CD4+ counts <200 cells/µL are not exclusionary.
Participants with moderate to severe hepatic impairment.
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.
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. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment.
All participants will be screened for syphilis.
•Participants with untreated secondary (late latent) or tertiary syphilis infection, defined as a positive RPR and a positive treponemal test without clear documentation of treatment, are excluded.
•Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor.
•Participants with primary syphilis or early latent secondary syphilis (acquired within the preceding year) who have a positive RPR test and have not been treated may be treated during the screening period and if completion of antibiotic treatment occurs during the screening period, may be allowed entry after consultation with the Medical Monitor. If antibiotic treatment cannot be completed before the screening window ends, subjects may be rescreened once following completion of antibiotic therapy for primary or early latent secondary syphilis. 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.
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.
Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis 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), whether negative or 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.
Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who require or qualify for immediate HCV treatment are excluded (see Section 5.3.1 for those co-infected participants who post entry into SOLAR decide treatment for HCV infection is warranted or desired either by the participant or by the treating physician.
Participants with HCV co-infection will be allowed entry into this study if: a.Liver enzymes meet entry criteria
For further points refer Protocol |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of participants with plasma HIV-RNA greater than or equal to 50 copies/mL as per Food and Drug Administration (FDA) Snapshot algorithm at Month 12 (OLI and BIK)/Month 11 (D2I) (Intent-to-Treat Exposed [ITT-E] population) |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
Proportion of participants with plasma HIV-1 RNA <50 c/mL (c/mL) at Month 6 and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I) using the FDA Snapshot algorithm (Intent-to-Treat Exposed [ITT-E] population).
Proportion of participants with protocol-defined confirmed virologic failure (CVF) through Month 6 and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I) .
Proportion of participants with HIV-RNA greater than or equal to 50 c/mL as per FDA Snapshot algorithm at Month 6, Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I) .
Absolute values and changes from Baseline in viral load and CD4+ cell count over time including Month 6 and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I).
Incidence of treatment emergent genotypic and phenotypic resistance to CAB, RPV, BIC, FTC, and TAF through Month 6 and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I).
Change from Baseline (Day 1) in renal and bone biomarkers at Months 6 and 12 (OLI and BIK)/Month 5 and Month 11 (D2I).
Change from Baseline in proportions of participants with Metabolic syndrome at Months 6 and 12 (OLI and BIK)/Month 5 and Month 11 (D2I) in each arm.
Change from Baseline in incident metabolic syndrome at Months 6 and 12 (OLI and BIK)/Month 5 and Month 11 (D2I).
Change from Baseline (Day 1) in homeostasis model of assessment-insulin resistance (HOMA-IR) at Months 6 and 12 (OLI and BIK)/Month 5 and Month 11 (D2I).
Preference for CAB LA + RPV LA every 2 months compared to a BIK single tablet regimen will be assessed using a preference questionnaire at Month 12 (OLI and BIK)/Month 11 (D2I) (or Withdrawal).
Change from baseline (Day 1) in total “treatment satisfaction” score, and individual item scores of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) at Month 6, and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I), (or Withdrawal).
Change in treatment satisfaction over time using the HIV Treatment Satisfaction Change Questionnaire HIVTSQc total score and individual item scores at Month 12 (OLI and BIK)/Month 11 (D2I) (or Withdrawal).
Change from Month 2 in Dimension scores (“Acceptance of ISRs”, “Bother of ISRs”, “Leg movement”, “Sleep and individual item scores assessing pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time will be assessed using the Perception of injection questionnaire (PIN) at Months 2, 6, and 12 (OLI)/Months 1, 5, 11 (D2I) (or Withdrawal).
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| 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 | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| BIC 50 mg + FTC 200 mg + TAF 25 mg oral, administered once daily until Month 12. |
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| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 61 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Austria |
| Belgium |
| Canada |
| France |
| Germany |
| Ireland |
| Italy |
| Japan |
| Netherlands |
| Spain |
| Switzerland |
| United Kingdom |
| United States |
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| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 27 |
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