Study of Safety and Pharmacokinetics in Healthy Volunteers and Safety, Tolerability and Antiviral Activity of VM-1500 in Patients With Human Immunodeficiency Virus-1 Infection

• ClinicalTrials.gov Identifier: NCT02485509
• Recruitment Status: Completed
• First Posted: June 30, 2015
• Last Update Posted: June 30, 2015
• Sponsor: Viriom
• Information provided by (Responsible Party): Viriom

Tracking Information

• First Submitted Date: June 18, 2015
• First Posted Date: June 30, 2015
• Last Update Posted Date: June 30, 2015
• Study Start Date: March 2013
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 25, 2015): Safety and tolerability of VM-1500 in adult healthy subjects and in patients with early-stage chronic HIV-1 infection based on analysis of AEs, laboratory values. [ Time Frame: about one and half month ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 25, 2015)

• Pharmacokinetic (PK) profile of VM-1500 in healthy subjects (Cmax, AUC, T1/2) and in HIV-1-infected patients. [ Time Frame: about one and half month ]
• Dose dependency between VM-1500 plasma levels and corresponding HIV RNA reduction with the administered dosages of VM-1500. [ Time Frame: about one and half month ]
• Virologic activity as measured by plasma HIV RNA following treatment for seven (7) days with VM-1500. [ Time Frame: about one and half month ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Safety and Pharmacokinetics in Healthy Volunteers and Safety, Tolerability and Antiviral Activity of VM-1500 in Patients With Human Immunodeficiency Virus-1 Infection
• Official Title: Phase Ib/IIa, Single-Centre, Placebo-Controlled Randomized Study of Safety and Pharmacokinetics in Healthy Volunteers and Safety, Tolerability and Antiviral Activity of VM-1500 in Patients With Human Immunodeficiency Virus-1 Infection
• Brief Summary: A combined Phase Ib and IIa randomized, placebo-controlled, double-blind study of VM-1500 in healthy subjects and in patients with HIV-1 infection that are antiretroviral therapy naïve.

Detailed Description

The study will be split into two parts:

Part I: A randomized, placebo-controlled, single dose, double-blind study in healthy volunteers with 20 mg followed by 40 mg after DSMB approval.

Healthy group: one dose with 1 PK day 12 health volunteers (total): 6 subjects will randomized (4:2) to VM-1500 20 mg or placebo. After DSMB approval, 6 subjects will be randomized (4:2) to VM-1500 40 mg or placebo Part II: A randomized, placebo-controlled, multiple dose, double-blind study for 7 days in patients with HIV infection who are antiretroviral therapy-naïve. After positive DMSB review the dose will be escalated from 20 mg to 40 mg once daily.

Patient group: 2 PK days (in-house) at day 1 and day 7 16 patients (total): 8 subjects will be randomized (7:1) to VM-1500 20 mg or placebo once daily for 7 days. After DSMB approval, 8 subjects will be randomized (7:1) to VM-1500 40 mg or placebo once daily for 7 days.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: HIV Infection

Intervention

Drug: VM-1500/Placebo

VM-1500 or Placebo

Study Arms

• Experimental: 20 mg VM-1500/Placebo Healthy group
  VM-1500 20 mg or placebo single dose.
  Intervention: Drug: VM-1500/Placebo
• Experimental: 40 mg VM-1500/Placebo Healthy group
  VM-1500 40 mg or placebo single dose.
  Intervention: Drug: VM-1500/Placebo
• Experimental: 20 mg VM-1500/Placebo Patient group
  VM-1500 20 mg or placebo once daily for 7 days.
  Intervention: Drug: VM-1500/Placebo
• Experimental: 40 mg VM-1500/Placebo Patient group
  VM-1500 40 mg or placebo once daily for 7 days.
  Intervention: Drug: VM-1500/Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 25, 2015): 28
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria for Healthy Subjects:

1. Male age between 18-40 years
2. Has been determined healthy by physical examination, assessment of drug abuse, medical history and vital signs
3. Has normal results for the following screening tests: complete blood count , blood urea nitrogen, serum creatinine , fasting blood sugar, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and urinalysis.
4. Negative result for hepatitis B, hepatitis C and HIV antibodies

5. Willing to participate and signed the informed consent form

   Inclusion Criteria for Patients:

6. Males or females aged 18 to 65 years
7. HIV-1 infection, as documented by a rapid HIV test or any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry
8. Antiretroviral therapy naïve.

Exclusion Criteria for Healthy Subjects:

1. Hepatic or kidney disorders or any other disease or disorder which may in the opinion of the Investigator interfere with the results of the study or threaten the health of volunteers;
2. Drug intake (including herbal drugs) during the last month;
3. Active alcohol or and/or drug abuse that, in the opinion of the site investigator, would interfere with adherence to study requirements;
4. Volunteers have taken any investigational drug at least 3 month prior to the start of the study;
5. Inability to understand the Protocol or follow its instructions;

Exclusion Criteria for Patients:

1. Currently has any active AIDS defining illness
2. Exclusionary resistance mutations defined as evidence of any major NNRTI mutations according to the current IAS list of HIV-1 Resistance Mutations Associated with Drug Resistance on any genotype; or evidence of significant NNRTI resistance on any phenotype performed at any time prior to study entry.
3. Patients who are expected to need systemic antiviral therapy at any time during their participation in the study.
4. Patients who have received an investigational drug for HIV, HIV vaccine, immunomodulators, systemic cytotoxic chemotherapy, or other investigational therapy within 30 days prior to study entry;
5. Acute or chronic viral hepatitis;
6. History or other evidence of renal disease.
7. Abnormal hematological and biochemical parameters within 30 days of Entry (Day 1).
8. Screening ECG QTc value 450 ms.
9. Consumption / administration of concomitant medication.
10. Active alcohol and/or drug abuse that, in the opinion of the site investigator, would interfere with adherence to study requirements.
11. Positive results on urine screen for drugs of abuse at Screening or Day 1
12. History of immunologically mediated disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Thailand

Administrative Information

• NCT Number: NCT02485509
• Other Study ID Numbers: VM-1500-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Viriom
• Original Responsible Party: Same as current
• Current Study Sponsor: Viriom
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Viriom
• Verification Date: June 2015