A Trial to Confirm a Sustained Virological Suppression Defined as HIV-RNA <50 Copies/ml of 3 Different Doses of Fozivudine in Context to a Standard Zidovudine Based Antiretroviral Therapy Regimen (FATI-01)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
German Federal Ministry of Education and Research
National Institute for Medical Research, Tanzania
Treichville Academic hospital center, Division of infectious and tropical diseases (SMIT)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Kumasi Centre for Collaborative Research (KCCR)
Bernhard Nocht Institute for Tropical Medicine
Pharmaceutical Company (Chiracon GmbH)
Pharmaceutical Company (STADA Vietnam Joint Venture Co. Ltd.)
Information provided by (Responsible Party):
Michael Hoelscher, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT01714414
First received: October 25, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

A prospective, multicenter, open, randomized Phase 2a trial to confirm a sustained virological suppression defined as HIV-RNA <50 copies/ml of 3 different doses of Fozivudine in context to a standard Zidovudine based antiretroviral therapy regimen after 24 weeks of treatment in ART naïve, non subtype B HIV-1 infected individuals from Tanzania and Ivory Coast.


Condition Intervention Phase
HIV-1 Infection
Drug: FZD
Drug: 3TC
Drug: EFV
Drug: AZT
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Open, Randomized Phase 2a Trial to Confirm a Sustained Virological Suppression Defined as HIV-RNA <50 Copies/ml of 3 Different Doses of Fozivudine in Context to a Standard Zidovudine Based Antiretroviral Therapy Regimen After 24 Weeks of Treatment in ART naïve, Non Subtype B HIV-1 Infected Individuals From Tanzania and Ivory Coast

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • Proportion of patients with plasma HIV RNA < 50 copies/ml [ Time Frame: at week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with plasma HIV RNA <50 copies/ml [ Time Frame: at week 8 and 12 ] [ Designated as safety issue: No ]
  • Proportion of patients with plasma HIV RNA < 400 copies/ml [ Time Frame: at week 8, 12 and 24 ] [ Designated as safety issue: No ]
  • Mean HIV log10 reduction compared to baseline [ Time Frame: at week 2, 4 and 8 ] [ Designated as safety issue: No ]
  • Variation of circulating total lymphocyte count [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]
  • Variation of circulating CD4+ lymphocyte count [ Time Frame: up to week 24 ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) before and after the first dose [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Various pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) will be assessed before the first treatment and during the course of 12 hours after the first treatment.

  • Pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) at steady state [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Various pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) will be assessed during the course of 12 hours after 4 weeks of treatment.

  • Proportion of clinical events stage 3 or 4 of WHO HIV classification [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
  • Number of participants with Adverse Events as Measure of safety and tolerability [ Time Frame: up to week 24 ] [ Designated as safety issue: Yes ]
    The number of Adverse Events and also the quality, severity and relatedness to study drug are documented and analysed.

  • Incidence of resistance mutations after confirmed treatment failure (confirmed HIV RNA > 1000 copies/ml [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FZD 600mg twice daily
FZD 3 tablets (600mg) twice daily / 3TC 1 tablet (150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
Drug: FZD
Other Name: Fozivudine
Drug: 3TC
Other Name: Lamivudine
Drug: EFV
Other Name: Efavirenz
Experimental: FZD 800mg once daily
FZD 4 tablets (800mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
Drug: FZD
Other Name: Fozivudine
Drug: 3TC
Other Name: Lamivudine
Drug: EFV
Other Name: Efavirenz
Experimental: FZD 1200mg once daily
FZD 6 tablets (1200mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
Drug: FZD
Other Name: Fozivudine
Drug: 3TC
Other Name: Lamivudine
Drug: EFV
Other Name: Efavirenz
Active Comparator: AZT twice daily
1 tablet Combivir(AZT 300mg/3TC 150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
Drug: 3TC
Other Name: Lamivudine
Drug: EFV
Other Name: Efavirenz
Drug: AZT
Other Name: Zidovudine

Detailed Description:

The study will evaluate four different oral 1st line antiretroviral regimens: three study arms will contain different doses of Fozivudine (FZD) plus Lamivudine (3TC) in a twice daily or once daily application plus once daily Efavirenz. The 4th study arm will contain standard Zidovudine (AZT)/Lamivudine (3TC) twice daily in a fixed dose combination plus once daily Efavirenz. The treatment duration will be 24 weeks.

In a pharmacokinetic Sub-Study Pharmacokinetic (PK) characteristics will be determined under controlled conditions in a sub population to evaluate PK values of the study drugs.

Primary Objective

The primary objective is to confirm a sustained virological suppression (HIV RNA <50 copies/ml) after 24 weeks of treatment between three different doses of Fozivudine (FZD) based antiretroviral 1st line treatment regimen in context to a standard Zidovudine (ZDV) based treatment regimen in non subtype B HIV-1 infected individuals from Africa.

Secondary Objectives

  1. HIV-RNA log10 reduction of HIV-RNA at 2, 4 and 8 weeks of treatment between different arms
  2. Virological response (HIV RNA <50 copies/ml) at 8 and 12 weeks of treatment between different arms
  3. Virological response (HIV RNA <400 copies/ml) at 8, 12 and 24 weeks of treatment between different arms
  4. Immunologic response: variation in CD4 lymphocytes between different arms
  5. Drug toxicity, particularly anaemia, neutropenia and gastrointestinal adverse events
  6. Resistance pattern for in patients with virological failure
  7. Clinical trial capacity building of African study sites within the FATI network
  8. Establishment of a Fozivudine Drug developing consortium (NET) including members of pharmaceutical manufacturers in Asia, Africa and Europe.
  9. Development and piloting of a capacity development monitoring and evaluation framework

Pharmacological Objectives

  1. Pharmacokinetic assessments after the first intake of study drugs in a subset of study participants (Pharmacokinetic sub study)
  2. Pharmacokinetic assessments at steady state after four weeks of study drugs in a subset of study participants (Pharmacokinetic sub study)

Study Population and Study Duration

A total of 120 ART naive HIV-1 infected individuals with the indication to start antiretroviral treatment according to WHO and country guidelines will be enrolled at two study sites in Côte d'Ivoire and Tanzania. Each of the two sites will enroll 60 participants (15 participants per arm). For the PK Sub-Study 6 participants per study arm (total 24 participants will be included.

A minimum of 30% gender representation (female or male) participants will be requested per site. Recruitment, screening and enrollment of study participants are expected to be completed after 9 months. Patient treatment is 24 weeks. So patient related study procedures will take 15 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female ≥ 18 years of age.
  2. Provide written or thump printed informed consent prior to all trial-related procedures
  3. HIV-1 positive with an indication to start antiretroviral therapy (ART) according to WHO and/or country guidelines
  4. ART naïve, including no history of antiretroviral medication during PMTCT or PEP
  5. Patient agrees not to take any concomitant medication during the trial without informing the investigator. Traditional medicines should be specified with concomitant medications.
  6. Availability throughout the study
  7. Female patients of childbearing potential must have a negative pregnancy test and agree to use a highly effective method of birth control throughout participation in the trial and for 10 weeks after last dose (to cover duration of ovulation).
  8. Agree to have home visits or active tracing if lost to follow up or any other event justifying a rapid visit of the patient at the clinical trial centre.
  9. CD4 count ≥100 cells/μl
  10. Hb ≥9.5 g/dl
  11. Platelets ≥50,000 cells/mm3
  12. Neutrophils ≥500 cells/ mm3
  13. Bilirubin <2.5 x uln
  14. ALT <2.5 x uln
  15. Exclusion of Severe hepatic insufficiency (PT<50%)
  16. Creatinine clearance calculated by Cockroft's formula ≥50 ml/min
  17. Urine dipstick for protein and blood: negative or trace

Exclusion Criteria:

  1. Deficiency in the patient, rendering it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
  2. Presence of an uncontrolled, ongoing, opportunistic infection or of any severe or progressive disease including active TB or any other justified reason which in the opinion of the investigator could significantly inhibit study procedures. This includes any clinical signs possibly associated with any WHO stage 3 or 4, with still unconfirmed diagnosis such as fever, weight loss, diarrhoea or unexplained cough.
  3. HIV-2 infection
  4. Pregnancy or lactating mother
  5. Unlikely to comply with protocol as judged by the principal investigator or his designate
  6. Use of experimental therapeutic agents within 30 days of study entry.
  7. Hepatitis B with positive HBsAg.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714414

Locations
Côte D'Ivoire
Service des Maladies Infectieuses et Tropicales, CHU de Treichville,
Abidjan, Côte D'Ivoire, BPV3
Tanzania
NIMR - Mbeya Medical Research Programme,
Mbeya, Tanzania, PO Box 2410
Sponsors and Collaborators
Michael Hoelscher
European and Developing Countries Clinical Trials Partnership (EDCTP)
German Federal Ministry of Education and Research
National Institute for Medical Research, Tanzania
Treichville Academic hospital center, Division of infectious and tropical diseases (SMIT)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Kumasi Centre for Collaborative Research (KCCR)
Bernhard Nocht Institute for Tropical Medicine
Pharmaceutical Company (Chiracon GmbH)
Pharmaceutical Company (STADA Vietnam Joint Venture Co. Ltd.)
Investigators
Study Director: Michael Hoelscher, Prof. Department for Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Leopoldstrasse 5, 80802, Munich, Germany
  More Information

No publications provided

Responsible Party: Michael Hoelscher, Chief Investigator, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01714414     History of Changes
Other Study ID Numbers: LMU-IMPH-FATI-01
Study First Received: October 25, 2012
Last Updated: January 27, 2014
Health Authority: Germany: Institutional Ethics review board of Munich University
Tanzania: National Health Research Ethics Review Committee
Tanzania: Mbeya Medical Research and Ethics Committee
Tanzania: Tanzania Food and Drugs Authority (TFDA)
Cote d'Ivoire: National Research and Ethics Committee

Keywords provided by Ludwig-Maximilians - University of Munich:
HIV
Fozivudine
Zidovudine
FATI

Additional relevant MeSH terms:
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on October 16, 2014