PILOT STUDY OF NOVEL COMBINATION OF MARAVIROC + ATAZANAVIR/RITONAVIR VS ATAZANAVIR/RITONAVIR + EMTRICITABINE/TENOFOVIR FOR THE TREATMENT OF TREATMENT NAÏVE HIV-INFECTED PATIENTS WITH R5 HIV-1

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2008-007038-24-DE
• Date of registration: 17/03/2009
• Prospective Registration: Yes
• Primary sponsor: ViiV Healthcare UK Limited
• Public title: PILOT STUDY OF NOVEL COMBINATION OF MARAVIROC + ATAZANAVIR/RITONAVIR VS ATAZANAVIR/RITONAVIR + EMTRICITABINE/TENOFOVIR FOR THE TREATMENT OF TREATMENT NAÏVE HIV-INFECTED PATIENTS WITH R5 HIV-1
• Scientific title: PILOT STUDY OF NOVEL COMBINATION OF MARAVIROC + ATAZANAVIR/RITONAVIR VS ATAZANAVIR/RITONAVIR + EMTRICITABINE/TENOFOVIR FOR THE TREATMENT OF TREATMENT NAÏVE HIV-INFECTED PATIENTS WITH R5 HIV-1
• Date of first enrolment: 12/06/2009
• Target sample size: 88
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007038-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Germany, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Provide a signed and dated written Informed Consent Document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial.
2. At least 16 years of age (or minimum age as determined by local regulatory authorities or as legal requirements dictate) at the Screening Visit.
3. HIV-1 RNA viral load of =1,000 copies/mL measured at the Screening Visit.
4. CD4 count =100 cells/mm3 at Screening.
5. Have only R5 HIV-1 at Screening as verified by the Monogram Bioscience Trofile assay with enhanced sensitivity.
6. A negative urine pregnancy test at the Baseline Visit, prior to receiving the first dose of study medication, for Women of Child Bearing Potential (WOCBP).
NOTE: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization or is not post-menopausal (ie, no menstrual periods for at least 2 years). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products (intrauterine devices; barrier methods: eg, condom or diaphragm with spermicide) to prevent pregnancy, who are practicing abstinence, or who have a partner that is sterile (eg, vasectomy), should be considered to be of child bearing potential.
7. Effective barrier contraception for WOCBP. In addition, WOCBP must use another acceptable method of contraception for the duration of the study. Acceptable contraception includes, but is not limited to, oral, implanted or injectable hormone therapy and intrauterine devices.
8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
1. Suspected or documented active, untreated HIV-1 related Opportunistic Infection(OI) or other condition requiring acute therapy (eg, acute hepatitis C virus infection)at the time of Randomization [Patients on a stable (>1 month) secondary OI prophylaxis regimen or chronic treatment with stable disease (eg, for hepatitis C virus infection) are eligible for the study; patients on a primary OI prophylaxis regimen of any duration are also eligible for the study].
2. Treatment for an active opportunistic infection, or unexplained temperature >38.5° C (101.3º F) for 7 consecutive days, within 30 days prior to Randomization. 3. Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time.
4. Active alcohol or substance abuse sufficient, in the Investigator’s judgment, to prevent adherence to study medication and/or Follow-Up.
5. Pregnant, breast feeding or planning to become pregnant.
6. Suspected primary (acute) HIV-1 infection.
7. Initiation of therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 60 days prior to Randomization or the expected need for such therapy during the study period. NOTE: Trimethoprim-sulfamethoxazole may not be initiated within 60 days prior to Randomization but may be continued if the subject is on stable therapy.
8. Malignancy requiring parenteral chemotherapy that must be continued for the duration ofthe trial.
9. Documented or suspected acute hepatitis or pancreatitis within 30 days prior to Randomization.
10. Renal insufficiency defined as a serum creatinine greater than 3 times the upper limit of normal or a creatinine clearance of less than 50 mL/min, as calculated by the Cockcroft and Gault equation.
11. Total bilirubin greater than 2 times the upper limit of normal. Changes of one or more grades in total bilirubin between Screening and the Randomization Visit should be reviewed with the Pfizer Medical Monitor before the initiation of study medication.
12. AST and/or ALT greater than 3 times the upper limit of normal. Changes of one or more grades in LFT results between Screening and Randomization should be reviewed with the Pfizer Medical Monitor before commencing dosing of study medications.
13. Cirrhosis of the liver, moderate or severe hepatic impairment (Child-Pugh classification B or C).
14. Hepatitis B surface antigen positive.
15. Absolute neutrophil count =750 cells/mm3.
16. Platelet count =50,000 cells/mm3.
17. Hemoglobin =7 g/dLl.
18. Clinically significant malabsorption syndrome (eg, =6 loose stools per day for at least 7 consecutive days) within 30 days prior to Randomization.
19. Inability to tolerate oral medication.
20. Concomitant therapy with other investigational agents.
21. Contraindicated medications being taken by the subject at the time of Randomization that must be continued during the study period, including immunomodulators (for the treatment of HIV-1 infection;), and any contraindicated medication described in the package inserts of maraviroc (Selzentry, Celsentri), atazanavir (Reyataz), ritonavir (Norvir) and emtricitabine/tenofovir (Truvada).
22. Any evidence of resistance to atazanavir, tenofovir, and emtricitabine.
23. X4-or dual/mixed-tropic virus by enhanced Trofile assay or repeated assay failure or not reportable results.
24. Any safety, behavioral, clinical, or administrative reasons that, in the Investigator’s judgm

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

Health Condition(s) or Problem(s) studied

TREATMENT OF TREATMENT NAÏVE HIV-INFECTED PATIENTS WITH R5 HIV-1
MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection

Intervention(s)

Trade Name: Celsentri
Product Name: Maraviroc
Product Code: UK-427,857
Pharmaceutical Form: Tablet
INN or Proposed INN: Maraviroc
CAS Number: 376348-65-1
Current Sponsor code: UK427,857
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Truvada
Product Name: Truvada
Pharmaceutical Form: Tablet
INN or Proposed INN: emtricitabine
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Tenofovir disoproxil
CAS Number: 147127-20-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 245-

Primary Outcome(s)

Secondary Objective: 1. Safety and tolerability;
2. To assess the viral kinetics within the first 2 weeks in the first 15 patients in each
treatment arms (US sites only);
3. To evaluate the pharmacokinetics of maraviroc in a subset of patients (n=15)enrolled in the maraviroc treatment arm (US sites only);
4. To assess virologic response over time;
5. To assess immunological response (CD4 and CD8 counts) over time;
6. To examine the evolution of viral resistance and/or tropism in treatment failure patients only.

Main Objective: To examine if the combination of maraviroc (SelzentryTM, Celsentri®) and atazanavir/ritonavir is effective for the treatment of treatment-naïve HIV-1 infected subjects as measured by the percentage of subjects with HIV-1 RNA below the limits of assay detection (<50 copies of HIV-1 RNA per milliliter of plasma) at 48 weeks.

Primary end point(s): The percentage of patients with plasma HIV-1 RNA <50 copies/mL in each treatment arm at 48 weeks.

Secondary ID(s)

A4001078