Long Acting Cabotegravir plus Rilpivirine in People Living with HIV-1 (PLHIV) Aged ≥ 60 Years for 96 weeks.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Virus Diseases [C02]

Trial duration

3 Mar 2025 → ongoing

Decision date (initial)

2025-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the proportion of participants ≥60 years on stable oral ART that switch to CAB LA + RPV LA with plasma HIV-1 RNA ≥50 copies/mL at month 12 in the intention-to-treat exposed (ITT-E) population, per the US FDA’s Snapshot algorithm.

Secondary objectives 14

1. To evaluate other estimations of virological control at months 6, 12 and 24.
2. To assess the factors associated with CVF.
3. To assess the incidence of treatment-emergent genotypic and phenotypic resistance in participants having CVF.
4. To evaluate the immune effects of switching to CAB LA + RPV LA at month 6, 12 and 24.
5. To evaluate the satefy and tolerabilty of CAB LA + RPV LA in this study.
6. To assess the change in metabolic control parameters at months 6, 12 and 24.
7. To evaluate the change in liver steatosis by CAP at months 12 and 24.
8. To evaluate the change in CV risk by Framingham REGICOR risk chart at months 12 and 24.
9. To assess adherence to study and IM injection visits through month 24.
10. To assess the change in PROs for HIV Treatment Satisfaction and Preference, and Perception of injection at months 6, 12 and 24.
11. To assess change in PROs exploring how a daily reminder/ change in modality could impact on people’s for stigma, FAD questions, anxiety and depression, loneliness, cognitive impairment, sleep disturbance, frailty and illness intrusiveness at months 12 and 24.
12. To evaluate the number of episodes of plasma HIV-1 RNA ≥50 copies/mL that do not meet the criteria for confirmed virological failure through the study.
13. The evaluate the number of participants experiencing Confirmed Virological Failures (CVF: two consecutive plasma HIV-1 RNA ≥200 copies/mL) through the study.
14. To assess the change in CD4/CD8 ratio from baseline to months 12 and 24.

Conditions and MedDRA coding

HIV-1

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Be able to understand and comply with protocol requirements, instructions, and restrictions.
2. Understand the long-term commitment to the study and be likely to complete the study as planned.
3. 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.).
4. Must be on a stable antiretroviral regimen without present or past evidence of viral resistance, and no prior virological failure with agents of the NNRTI and INI class.
5. Plasma HIV-1 RNA <50 copies/mL at screening.
6. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum hCG test at screening) and not lacting.
7. Adults ≥60 years, currently receiving an antiretroviral regimen for ≥6 months.
8. Patients who have given written informed consent.

Exclusion criteria 26

1. Plasma HIV-1 RNA measurement ≥50 copies/mL within 6 months prior to screening. Blips are allowed (increased viral load ≥50 copies/mL but <200 copies/mL preceded and followed by a viral load less than 50 copies/mL)
2. Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal 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).
3. Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternative medication (refer to section 11.1.4. for additional information)
4. History of liver cirrhosis with or without hepatitis viral co-infection.
5. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
6. No clinically important pharmacokinetic differences between subjects with severe renal impairment (CrCL <30 mL/min and not on dialysis) and matching healthy subjects were observed. No dosage adjustment is necessary for patients with mild to severe renal impairment (not on dialysis). Cabotegravir has not been studied in patients on dialysis.
7. Subjects with HCV co-infection were allowed entry into this study if liver enzymes meet entry criteria.
8. Subjects with HCV co-infection were allowed entry into this study if investigators should consult current treatment guidelines when considering choice of therapy for individuals with chronic hepatitis C virus infection. Participants with hepatitis C virus infection should have undergone appropriate work-up, the chronic hepatitis C infection should not be advanced, and not anticipated to require introduction of new HCV therapy (e.g. with oral direct acting antivirals) during the course of the study
9. Any evidence of primary resistance based on the presence of any major known INSTI or NNRTI resistance-associated mutation.
10. Any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the subject’s participation in the study of an investigational compound.
11. Subject has estimated creatinine clearance <50mL/min per 1.73m2 via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) method.
12. Subjects who are currently participating in or anticipate being selected for any other interventional and non-interventional study Observational studies and clinical trials that do not include treatments are allowed.
13. Alanine aminotransferase (ALT) ≥5 × upper limit of normal (ULN). Or ALT ≥3x ULN and bilirubin ≥1.5x ULN (with >35% direct bilirubin).
14. Subjects who, in the investigator's judgment, posed a significant suicide risk. Subject’s recent history of suicidal behaviour and/or suicidal ideation should be considered when evaluating for suicide risk.
15. Any drug holiday during the window between initiating first HIV ART and 6 months prior to screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
16. Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to NNRTI or INSTI (defined as a confirmed plasma HIV-1 RNA measurement ≥200 copies/mL after initial suppression to <50 copies/mL while on first line HIV therapy regimen)
17. Subjects with HCV co-infection were allowed entry into this study if additional information (where available) on subjects with HCV co-infection at screening should include results from any liver biopsy, FibroScan-CAP, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.
18. Subjects with HCV co-infection were allowed entry into this study if in the event that recent biopsy or imaging data is not available or inconclusive, the FIB-4 score will be used to verify eligibility.  FIB-4 score >3.25 is exclusionary.  FIB-4 scores 1.45–3.25 requires medical monitor consultation fibrosis 4 score. Formula: (Age x Aspartate aminotransferase) / (Platelets x (sqr [alanine aminotransferase]).
19. Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the investigator, may interfere with the subject’s ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject.
20. 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 subject unable to receive study medication.
21. History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled.
22. Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and platelet disorders such as haemophilia or Von Willebrand Disease.
23. The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.
24. 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: Subjects positive for HBsAg are excluded. Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
25. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection were not excluded. Treatment for HCV is allowed if the patient requires it during the development of the study.
26. Subjects deemed at high risk of seizure (such as those with an existing poorly controlled seizure disorder, or considered at high risk of recurrence based on medical history).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of PLHIV ≥ 60 years on stable ART that switch to CAB LA + RPV LA with plasma HIV-1 RNA ≥50 copies per mL at month 12 in the intention-to-treat exposed (ITT-E) population, per the US Food and Drug Administration’s Snapshot algorithm.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Sponsor organisation

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Address

Carretera De Cartagena S/n, El Palmar El Palmar

City

Murcia

Postcode

30120

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Contact name

María Muñoz García

Public contact point

Organisation

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Contact name

María Muñoz García

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications