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Trial registered on ANZCTR


Registration number
ACTRN12608000258358
Ethics application status
Approved
Date submitted
19/05/2008
Date registered
21/05/2008
Date last updated
4/11/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Clinical study to assess the efficacy and safety of a new antiretroviral drug (MPC-4326) in patients with Human immunodeficiency virus-1 (HIV-1) infection over a period of 14 days to 72 weeks.
Scientific title
title: A Phase II multicenter, open-label, randomized, parallel group, study of MPC-4326 in HIV-1 positive patients to evaluate the safety, efficacy, and pharmacokinetics of MPC-4326 administered as monotherapy for 14 days and as part of an optimized background regimen for up to 72 weeks.
Secondary ID [1] 562 0
Eudract no: 2007-007152-34
Universal Trial Number (UTN)
Trial acronym
BVM 204
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1 3169 0
Condition category
Condition code
Infection 3326 3326 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
MPC-4326 (code name) 200mg BID (twice daily) and 300mg BID doses of MPC-4326(tablets). Total duration of bevirimat treatment is 14 days minimum (monothereapy) to 72 weeks maximum (together with an optimised background regiment). Total planned duration of the study is approximately 7 weeks minimum to 81 weeks maximum.
Intervention code [1] 2898 0
Treatment: Drugs
Comparator / control treatment
N/A as neither a comperator nor a placebo will be used.
Control group
Dose comparison

Outcomes
Primary outcome [1] 4214 0
Evaluate antiretroviral activity and safety administered as momotherapy for 14 days. Primary efficacy endpoint is defined as the mean change in viral load (HIV-1 Ribonucleic acid (RNA) log10 copies/mL0 from baseline at day 15).
Timepoint [1] 4214 0
At screening, baseline, day 1, 3, 7, 10 and 15.
Secondary outcome [1] 7130 0
Evaluate antiretroviral activity and safety for 72 weeks. Secondary efficacy endpoint is defined as the mean change in viral load (HIV-1 RNA (Ribonucleic acid) log10 copies/mL from baseline at weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, End of study visit)
Timepoint [1] 7130 0
At weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, End of study visit)
Secondary outcome [2] 7131 0
Explore the dependence of response on baseline HIV-1 Ribonucleic acid (RNA) levels, genotype and phenotype. Proportion of patients achieving 1.0 log10 reduction in viral load at weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, End of study visit. Proportion of patients with plasma HIV-1 RNA levels < 400 copies/ml at weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, End of study visit)
Timepoint [2] 7131 0
At weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, End of study visit)
Secondary outcome [3] 7132 0
To evaluate the emergence of mutations in HIV leading to resistance to MPC-4326 or other components of patient's treatment regimen. Measured as the proportion of patients with treatment-emergent resistant mutations in HIV RT (HIV Reverse Transcriptase), Protease, gp120 and CA-SP1 (Caspase1) at week 2; other timepoints will be analysed according to the profile of results observed.
Timepoint [3] 7132 0
At screening, baseline, Day1, 3, 7, 10 and 14.

Eligibility
Key inclusion criteria
- documented HIV-1-infection
- a CD4+-lymphocyte count =100 cells/mm3
- a screening plasma HIV-1 RNA value of 2,000 – 500,000 copies/mL.
- treatment-experienced patients must have documented evidence of genotypic resistance in their medical records (at screening) or have a resistance-associated primary mutation at screening by genotype to at least one approved ARV (Anti-retroviral) drug identified on the most recent IAS-USA l(international AIDS society USA) ist of resistance drug mutations
- For treatment-experienced patients: be receiving an antiretroviral therapy regimen containing at least 3 drugs which has been unchanged for at least 8 weeks prior to initial screening. Note: A washout period of at least 3 days prior to Day 1 of dosing is required.
- treatment-naïve patients: no previous antiretroviral treatment.
- Be able to receive an optimized background regimen
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Current opportunistic infection characteristic of AIDS that is diagnosed within 30 days or is poorly controlled.
- unable to comply with the dosing schedule and protocol evaluations.
- with malabsorption syndromes affecting drug absorption
- A history of seizures or current administration of prophylactic anti-seizure medications.
- history of cerebrovascular accident (CVA) or transient ischemic attacks (TIA).
- must have laboratory parameters within pre-specified limits.
- Patients who have received treatment with immunomodulating agents within 4 weeks prior to the first dose of study drug.
- Patients who have ever received an HIV immunotherapeutic vaccine.
- Recent use of any recreational drugs (except marijuana), or positive results from a urine screen for substances of abuse
- Bupropion-containing products require at least a 14-day washout period.
- Rifampin or other rifamycin products require at least a 28-day washout period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be randomized to either 200 mg BID or 300 mg BID doses of MPC-4326. The randomization will occure central by phone via an interactive voice response system (IVRS), which needs to be called by the site staff for each patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Central stratification (IVRS) of the patients by prior antiretroviral use (treatment-experienced vs. treatment-naïve). Equal numbers of patients will be randomized to each treatment group within each stratum.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 679 0
2010
Recruitment postcode(s) [2] 680 0
3004
Recruitment outside Australia
Country [1] 971 0
New Zealand
State/province [1] 971 0
Country [2] 972 0
Belgium
State/province [2] 972 0
Country [3] 973 0
Poland
State/province [3] 973 0

Funding & Sponsors
Funding source category [1] 3396 0
Commercial sector/Industry
Name [1] 3396 0
Myriad Pharmaceuticals Inc.
Address [1] 3396 0
320 Wakara Way, Salt Lake City, UT 84108
Country [1] 3396 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Myriad Pharmaceuticals Inc.
Address
320 Wakara Way, Salt Lake City, UT 84108
Country
United States of America
Secondary sponsor category [1] 3043 0
None
Name [1] 3043 0
Address [1] 3043 0
Country [1] 3043 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5427 0
Bellberry Limited HREC
Ethics committee address [1] 5427 0
First Floor
71 Anzac Highway
Ashford SA 5035
Ethics committee country [1] 5427 0
Australia
Date submitted for ethics approval [1] 5427 0
29/01/2008
Approval date [1] 5427 0
05/03/2008
Ethics approval number [1] 5427 0
B12/08

Summary
Brief summary
The main purpose of this research study is to evaluate the antiretroviral (how effective the drug is at reducing the amount of HIV in the blood) activity of two different doses of MPC-4326 in HIV-1 positive participants and what, if any, side effects there may be through 14 days of dosing. This study will also evaluate the antiretroviral activity and safety of bevirimat in participants who continue treatment with bevirimat as part of combination highly active antiretroviral therapy for up to 72 weeks. We also want to know how much of the drug gets into your blood stream following oral administration. We are asking participants who will start their treatment for the first time (so called naïve (exposed to treatment for the first time) participants) and who are already on treatment (treatment experienced participants) to participate. If you choose to participate in this study and do not intend to continue MPC-4326 treatment past 14 days, you should not expect any medical benefits from taking part in this study and it is even possible that your HIV could worsen during the study. The potential benefit to society may be information gained on the safety and effectiveness of the study treatment for patients in the future. However, if you choose to participate in this study and intend to continue MPC-4326 treatment past 14 days should your viral load reduction in those first 14 days be at least two-thirds or 66.6% as compared with your viral load value at baseline, then you may have medical benefits from taking part in this study. These possible benefits include a persistent viral load reduction and an improvement in the CD4 count (a blood marker of immune system health) that may occur. As this is an experimental medication, the likelihood of these benefits occurring for you is not yet known.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28599 0
Address 28599 0
Country 28599 0
Phone 28599 0
Fax 28599 0
Email 28599 0
Contact person for public queries
Name 11756 0
Silvia Gurrieri
Address 11756 0
Quintiles PTy Limited
Level 8&9
67 Albert Avenue
Chatswood, NSW 2067
Country 11756 0
Australia
Phone 11756 0
+61 2 9016 8245
Fax 11756 0
+61 2 9016 8106
Email 11756 0
silvia.gurrieri@quintiles.com
Contact person for scientific queries
Name 2684 0
Andrew Beelen
Address 2684 0
320 Wakara Way, Salt Lake City, UT 84108
Country 2684 0
United States of America
Phone 2684 0
+1 801-505-5078
Fax 2684 0
Not applicable
Email 2684 0
andrew.beelen@myriadpharma.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary