PROTEA: A clinical trial comparing the efficacy of darunavir/ritonavir 800/100 mg monotherapy versus a triple combination therapy containing darunavir/ritonavir 800/100 mg and 2 nucleoside/nucleotide reverse transcriptase inhibitors in patients with undetectable plasma HIV-1 RNA on current treatment

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2011-001635-23-DE
• Date of registration: 22/09/2011
• Prospective Registration: Yes
• Primary sponsor: Janssen Cilag International N.V.
• Public title: PROTEA: A clinical trial comparing the efficacy of darunavir/ritonavir 800/100 mg monotherapy versus a triple combination therapy containing darunavir/ritonavir 800/100 mg and 2 nucleoside/nucleotide reverse transcriptase inhibitors in patients with undetectable plasma HIV-1 RNA on current treatment
• Scientific title: PROTEAse inhibitor (DRV/rtv) in mono- or triple therapy in suppressed HIV-1 infected subjects
• Date of first enrolment: 31/08/2012
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001635-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: monotherapy vs triple combination therapy Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Denmark, Germany, Hungary, Ireland, Israel, Italy, Poland, Spain, Sweden, Switzerland, United Kingdom

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen Biologics

• Name: Clinical Registry Group
• Affiliation: Janssen Biologics

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have documented HIV-1 infection.
2. Be male or female aged 18 or over 18 years old.
3. Criterion deleted per amendment.
4. Criterion modified per amendment.
4.1 Currently be receiving HAART for at least 48 weeks.
5. Criterion modified per amendment.
5.1 Have at least 2 documented plasma HIV-1 RNA <50 copies/mL, and no HIV-1 RNA 50 or over 50 copies/mL in the 48 weeks prior to the screening visit.
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: CNS, 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. Criterion modified per amendment.
8.1 Have no CD4+ cell counts below 100 cells/mm3, from the time of first known HIV infection to the start of HAART, and >200 cells/mm3 at screening or a maximum of 4 weeks prior to 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 ß-human chorionic gonadotropin (ß-hCG) 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. Criterion modified per amendment.
12.1 Have voluntarily signed and dated 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 255
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Criterion modified per amendment.
1.1 Has a history of virologic failure defined as 2 consecutive plasma HIV-1 RNA >500 copies/mL after initial viral suppression while on previous or current antiretroviral therapy.
2. Has a history of any primary PI mutations as defined by the IAS-USA guidelines 2010.24
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 (DAIDS) grading table (see Attachment 1: DAIDS AE 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 (CDC) 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. Criterion modified per amendment.
14.1 Has a severe depression (based on test results from the BDI: scoring between 30 and 63).
15. Has previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (DRV).
16. Is hypersensitive to ritonavir or to any of the other ingredients found in the ritonavir tablet.
17. Uses disallowed concomitant therapy (see Section 8 and DRV Summary of Product Characteristics [SPC]25).
18. Is currently enrolled in an investigational drug study or has participated in such study within 30 days before screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

HIV-1 infection
MedDRA version: 15.1 Level: LLT Classification code 10020192 Term: HIV-1 System Organ Class: 100000004862

Intervention(s)

Trade Name: Prezista
Product Name: darunavir-film coated tablet-400mg (F030)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DARUNAVIR
CAS Number: 206361-99-1
Current Sponsor code: Darunavir ethanolate (formerly known as TMC114 ethanolate)
Other descriptive name: DRV (formerly known as TMC114)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Norvir®
Product Name: ritonavir
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RITONAVIR
CAS Number: 155213-67-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

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

Primary end point(s): the percentage of patients 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

Secondary Objective: 1. 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
2. change in neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks
3. 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.
4. 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
5. the loss of treatment options as defined by treatment-emergent phenotypic drug resistance
6. the viral genotype of subjects
7. To evaluate and compare safety and tolerability

Timepoint(s) of evaluation of this end point: 48 weeks

Secondary Outcome(s)

Secondary end point(s): 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

change in neurocognitive function of DRV/rtv monotherapy versus
triple therapy containing DRV/rtv over 48 and 96 weeks

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.

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

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

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

Timepoint(s) of evaluation of this end point: 48 weeks en 96 weeks

Secondary ID(s)

2011-001635-23-GB

TMC114IFD3003

Source(s) of Monetary Support

Janssen Medical Affairs