Safety, PK and PD Study of ABX464 in Untreated HIV Patients

Study Overview
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Brief Summary
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ABX464 is a first in class that showed efficacy as an anti-HIV therapy. The present study is intended to assess the safety, the tolerability, and pharmacokinetic parameters and to evaluate the effect on viral load of repeated oral administrations of ABX464 in patients infected by HIV, not previously treated for their HIV. Two types of design are intended in this protocol: dosing every 3 days or dosing every day. The goal is to determine the best dosing regimen to reduce viral load and minimize adverse events.

Official Title
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A Phase 2, Dose Escalation, Schedule Comparison Study to Evaluate the Safety, Pharmacokinetics, and Viral Kinetics of ABX464 in Untreated Patients With HIV Infection in Mauritius

Conditions
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Human Immunodeficiency Virus Infections

Intervention / Treatment
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* Drug: ABX464
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, 18 to 65 years of age Patients infected by HIV-1 or HIV-2 BMI between 17 and 29 kg/m². CD4 cell count ≥ 350 /mm3 and HIV RNA level between 5,000-500,000 copies/mL. Clinical laboratory tests (hematology, blood chemistry, and urinalyses) must be within normal limits, or clinically acceptable to the sponsor and principal investigator and consistent with the underlying HIV infection. Urine drug screen for drugs with a high potential for abuse (cocaine, opiates, amphetamines and barbiturates) and alcohol breath test must be negative. Females must be non lactating and either be of nonchildbearing potential (ie sterilized via hysterectomy or bilateral tubal ligation or at least one year post-menopausal) or if of child bearing potential, must be practicing effective double barrier contraceptive methods from at least two weeks prior to Day 1 until 3 months after the last dose of study medication. Males must practice an effective barrier method of contraception from Day 1 until 3 months days after the last dose of study medication. Patients must be willing to give written informed consent prior to study enrollment and be able to adhere to restrictions and examination schedules. Physical examination and ECG must be within normal limits. Never taken any antiretroviral agent except for a brief time, and for some reasons, the patient decided not to continue therapy (i.e. Toxicity, personal decision. None in past 30-180 days. Exclusion Criteria: Individuals with a history of any significant medical disorders which requires a physician's care. Individuals who have a history of any clinically significant local or systemic infectious disease (other than HIV-1 or HIV-2 infection) within four weeks prior to drug administration. Individuals with any clinically significant laboratory abnormalities as defined as grade 2 or 3 in Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Individuals who are positive for hepatitis B virus and/or hepatitis C virus Any individual who does not comply with the requirement that he should not have used any drugs (including prescription, nonprescription, herbal, and mineral supplements) other than paracetamol for at least two weeks prior to the study nor alcohol within 48 hours prior to drug administration and for the entire study period. The use of a concomitant medications to treat an AE during the study will not be considered a protocol violation. Individuals who have participated in a clinical trial of an investigational drug within 90 days prior to the start of the study Individuals who smoke more than ten cigarettes or equivalent tobacco use per day. Individuals with forfeiture of freedom by an administrative or legal obligation or under guardianship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX464<br> | Drug: ABX464<br>* 25, 50, 75, 100, 150 mg, i.e. 1, 2, 3, 4 or 6 capsules respectively, every 3 days or every day for 2 weeks<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 1, 2, 3, 4 or 6 capsules respectively, every 3 days or every day for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability profile of ABX464 as assessed by the change from baseline in laboratory values, in vital signs and ECG parameters at week 3 and by the number of patients with adverse events. | Number of patients with abnormal blood (hematology and biochemistry) and urinary laboratory values, abnormal vital signs and ECG parameters and the number/proportion of patients reporting any adverse event. | Week 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration in plasma of ABX464 and metabolite | week 1, week 2 and week 3 | 
| tmax | Time to maximum concentration | Week 3 | 
| AUC | Area under the concentration-time curve | Week 3 | 
| t1/2 | Half-life of the ABX464 in plasma | Week 3 | 
| Pharmacodynamic activity as expressed by CD4 and CD8 count | CD4 and CD8 values | Week 3 | 
| Pharmacodynamic activity as expressed by HIV viral load | HIV viral load across time and possible relationship with PK parameters | Week 3 |