Clinical trial NCT04240210: Integrase Regimen Switch to Symtuza to Increase Tolerability/Adherence (SYMita)
Official title: SymITA: Switch to DRV/COB/FTC/TAF From Integrase Containing Regimens to Evaluate Changes in Tolerability/Adherence
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus
Lead sponsor: Midland Research Group, Inc.
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceuticals
First posted: 2020-01-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COB/FTC/TAF) is a coformulated STR, is the only protease inhibitor based STR, and is noted for its high tolerability3. These traits have the potential to improve adherence in patients who have intolerance to the integrase inhibitor class. We propose a two part study design to evaluate if patients who have suboptimal adherence due to integrase inhibitor intolerance may better tolerate Symtuza and subsequently have improved adherence.

Detailed description: With the advent of anti-retroviral therapy, HIV transformed into a manageable chronic disease for patients who were able to obtain medications, provided they could remain adherent to them. When single tablet regimens (STR) became available, adherence to HIV medications was made easier for many patients. However even years after STR became available, 38% of patients reported they do not maintain optimal adherence to their HIV medications. While there are many factors that contribute to this problem, medication intolerance contributes to suboptimal adherence for many patients

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza) is a coformulated STR, is the only protease inhibitor based STR, and is noted for its high tolerability. This trait has the potential to improve adherence in patients who have intolerance to the integrase inhibitor class. We are not aware of any studies that have examined this potential and find that information gap worth investigating.

We propose a two part study design to evaluate if patients who have suboptimal adherence due to integrase inhibitor intolerance may have better tolerability to Symtuza and subsequently have improved adherence.

The initial portion of the study will consist of a self-administered adherence survey offered over a 4 month period to established patients at Midland Medical Center who are HIV+, regardless of disease state or regimen. Subjects who self-identify as non-adherent due to tolerability issues will be screened for enrollment in the primary study. Subjects found to be non-adherent due to other issues will be referred back to their provider.

Subjects who are referred for screening who are on an integrase inhibitor and who do not have a contraindication will be enrolled, will complete a Patient Reported Outcome survey (PRO) to assess side effects/quality of life, and switched to Symtuza. Subjects who are not enrolled in the study will be referred back to their provider to address the issues with tolerance and adherence.

Subjects will be followed for 4 months. During that period, they will be brought back for evaluation at the end of the first month and the end of the fourth month. At those evaluations, they will again complete the PRO and adherence surveys to assess tolerability and adherence. At the evaluations, they will also be monitored for safety and effectiveness via physical exams and laboratory studies (Complete Blood Count, Complete Metabolic Panel, Urinalysis, CD4 panel, HIV1 Quantitative viral load).

The de-identified laboratory and survey results from the baseline and subsequent assessments will be turned over to a statistician to evaluate changes in adherence, tolerability, effectiveness, and safety.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age.
* HIV positive receiving ART of any type.
* Currently on an integrase containing regimen AND Reports non-adherent due to medication intolerance.
* GFR≥30mL/min.
* AST/ALT ≤ 3 times upper limit of normal. (AST- U/L 10-40), (ALT- U/L 9-46)
* Total bilirubin of ≤1.5 mg/dL.

Exclusion Criteria:

* Known resistance to darunavir or tenofovir
* Known intolerance to Symtuza or its components
* Current pregnancy
* Requires continued use of any of the agents in table 6.2.3.2.4
* Cirrhosis, regardless of compensation status
* Active, serious infections within 30 days of baseline
* History of malignancy within 5 years of baseline, except cutaneous Kaposi's sarcoma, basal cell or resected non-invasive cutaneous squamous cell carcinoma
* Life expectancy of less than a year
* Participation in any other investigation study 30 days prior to enrollment

Primary outcomes:
measure: Part 1 of the study is a cohort survey of change in adherence, tolerability and safety of subjects who report poor adherence to ART due to intolerance/side effects from integrase inhibitor containing regimens.
timeFrame: 4 months
Secondary outcomes:
measure: To determine potential changes in ART adherence in subjects who report sub-optimal adherence due to side effects from integrase containing regimens after switching to Symtuza.
timeFrame: 4 months
measure: To evaluate the tolerability of switching from an integrase inhibitor containing regimen to Symtuza.
timeFrame: 4 months
measure: Safety and efficacy of switching from integrase inhibitor containing regimen to Symtuza as determined by the proportion of subjects with virologic failure, a change in laboratory parameters and change in CD4 cell count from baseline.
timeFrame: 4 months
measure: To evaluate for potential weight loss when switching from integrase inhibitor containing regimen to Symtuza.
timeFrame: 4 months
Other outcomes:
Locations:
city: Oakland Park
country: United States
facility: Midland Research Group, Inc
state: Florida
Study officials:
affiliation: Midland Research Group
name: Anthony Ciesielski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ortego C, Huedo-Medina TB, Llorca J, Sevilla L, Santos P, Rodriguez E, Warren MR, Vejo J. Adherence to highly active antiretroviral therapy (HAART): a meta-analysis. AIDS Behav. 2011 Oct;15(7):1381-96. doi: 10.1007/s10461-011-9942-x.
citation: Robbins RN, Spector AY, Mellins CA, Remien RH. Optimizing ART adherence: update for HIV treatment and prevention. Curr HIV/AIDS Rep. 2014 Dec;11(4):423-33. doi: 10.1007/s11904-014-0229-5.
citation: Orkin C, Molina JM, Negredo E, Arribas JR, Gathe J, Eron JJ, Van Landuyt E, Lathouwers E, Hufkens V, Petrovic R, Vanveggel S, Opsomer M; EMERALD study group. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-e34. doi: 10.1016/S2352-3018(17)30179-0. Epub 2017 Oct 6.