PROTEA

Purpose / Objectives

Primary Outcome

 The primary objective is to demonstrate non-inferiority in terms of the percentage of subjects who have plasma human immunodeficiency virus type-1 (HIV-1) ribonucleic acid (RNA) levels <50 copies/mL after 48 weeks of follow-up after switching to DRV/ritonavir (rtv) monotherapy versus triple therapy containing DRV/rtv (FDA Snapshot method).

Secondary Outcomes

 

To evaluate the correlation of plasma HIV-1 RNA, cerebrospinal fluid (CSF) HIV-1 RNA, and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Week 48.

• To evaluate and compare change in neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks. 

• To evare the rate of plasma HIV-1 RNA suppression after 48 and 96 weeks of follow-up to DRV/rtv monotherapy versus triple therapy containing DRV/rtv, using the time to loss of virologic response (TLOVR) method.

• To evaluate the correlation of plasma HIV-1 RNA and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96.

• To compare the loss of treatment options of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96, as defined by treatment-emergent phenotypic drug resistance.

• To assess evolution of the viral genotype of subjects treated with DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks.

• To evaluate and compare safety and tolerability of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks.

Diagnosis

• HIV-1

HIV positive patients

Target population

Disease stage

treated patients

Age

18-99

Inclusion criteria

1. Have documented HIV-1 infection.

2. Be male or female aged ≥18 years old.

3. Have voluntarily signed and dated the consent form.

4. Currently be receiving HAART for at least 48 weeks

5. Have plasma HIV-1 RNA <50 copies/mL for at least 48 weeks prior to screening (2 results must be documented).

6. Be taking the same ARV combination for at least 8 weeks before screening.

7. Have the preference, together with the physician, to change the current HAART regimen for reasons of simplification and/or toxicity (examples of toxicities include but are not limited to: central nervous system, gastrointestinal disturbances, jaundice, anemia, nausea, neuropathy, paresthesia, hyperlipidemia, glucose intolerance or diabetes, nephrolithiasis, lipodystrophy, hepatotoxicity, rash and skin related events, any other AE or intolerability or laboratory abnormalities caused by current HAART).

8. Have CD4+ >100/mm³ at the start of HAART and >200/mm³ at screening.

9. Be able to comply with the protocol requirements. In particular, subjects should be willing to be followed up to Week 96 even if they discontinue randomized treatment.

10. If heterosexually active, a female of childbearing potential and a non-vasectomized male subject who has a female partner of childbearing potential must agree to use effective contraceptives from screening onwards until 30 days after completion of study treatment.

11. If a woman of childbearing potential, she must have a negative serum β-human chorionic gonadotropin pregnancy test at screening; and a negative serum or urine pregnancy test before the first dose of study medication to ensure they are not pregnant at the time of starting treatment.

12. Sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion criteria

1. Has a history of virologic failure defined as 2 consecutive plasma HIV-1 RNA >500 copies/mL while on previous or current antiretroviral therapy.

2. Has a history of any primary PI mutations as defined by the IAS-USA guidelines 2010.

3. Has clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency).

4. Is diagnosed with acute viral hepatitis at screening or before Baseline 1.

5. Is co-infected with hepatitis B.

6. Has documented hepatic cirrhosis.

7. Has a grade 3 or 4 laboratory abnormality as defined by the Division of AIDS grading table, with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:

• Subjects with pre-existing diabetes or with asymptomatic glucose grade 3 or 4 elevations.

• Subjects with asymptomatic triglyceride or cholesterol elevations of grade 3 or 4.

• Subjects taking atazanavir with asymptomatic hyperbilirubinemia of grade 3 or 4.

8. Has presence of any currently active AIDS defining illness (Category C conditions according to the Centers for Disease Control Classification System for HIV Infection 1993) with the following exceptions:

• Stable cutaneous Kaposi’s Sarcoma (ie, no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study.

• Wasting syndrome due to HIV infection.

9. Is a woman who is pregnant or breastfeeding.

10. Is an active drug abuser, including alcohol or recreational drugs.

11. Has any active clinically significant disease (eg, tuberculosis, cardiac dysfunction, pancreatitis, acute viral infections) or life threatening disease or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the subject’s safety or outcome of the study.

12. Has any medical or psychiatric condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol.

13. Is on anti-psychotic drugs.

14. Has a severe depression (based on test results from the BDI).

15. Has previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (DRV).

Note: DRV is a sulfonamide. Subjects who have previously experienced a sulfonamide allergy will be allowed to enter the study. To date, no potential for cross-sensitivity between drugs in the sulfonamide class and DRV has been identified in subjects participating in Phase 2 studies.

16. Is hypersensitive to ritonavir or to any of the other ingredients found in the ritonavir tablet.

17. Uses disallowed concomitant therapy.

18. Is currently enrolled in an investigational drug study or has participated in such study within 30 days before screening.

Study design

• Phase III
• Multicenter
• Prospective
• Open Label
• Randomized

Intervention

Treatment with Darunavir/r

Documents (password protected)

Go to download area

Responsibilities in overall study

Sponsor

Janssen-Cilag International N.V.

(National) Coordinating Investigator

Prof. Dr. med. Jürgen K. Rockstroh