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

NCT01714414 | Completed Phase 2 DMC

• 1 other identifier: LMU-IMPH-FATI-01
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

HIV-1 Infection

Keywords

HIV; Fozivudine; Zidovudine; FATI

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with plasma HIV RNA < 50 copies/ml

  at week 24

Secondary Outcomes (10)

• Proportion of patients with plasma HIV RNA <50 copies/ml

  at week 8 and 12

• Proportion of patients with plasma HIV RNA < 400 copies/ml

  at week 8, 12 and 24

• Mean HIV log10 reduction compared to baseline

  at week 2, 4 and 8

• Variation of circulating total lymphocyte count

  up to week 24

• Variation of circulating CD4+ lymphocyte count

  up to week 24

Study Arms (4)

FZD 600mg twice daily

EXPERIMENTAL

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; Drug: 3TC; Drug: EFV

FZD 800mg once daily

EXPERIMENTAL

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; Drug: 3TC; Drug: EFV

FZD 1200mg once daily

EXPERIMENTAL

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; Drug: 3TC; Drug: EFV

AZT twice daily

ACTIVE COMPARATOR

1 tablet Combivir(AZT 300mg/3TC 150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks

Drug: 3TC; Drug: EFV; Drug: AZT

Interventions

FZD DRUG

Also known as: Fozivudine

FZD 1200mg once daily; FZD 600mg twice daily; FZD 800mg once daily

3TC DRUG

Also known as: Lamivudine

AZT twice daily; FZD 1200mg once daily; FZD 600mg twice daily; FZD 800mg once daily

EFV DRUG

Also known as: Efavirenz

AZT twice daily; FZD 1200mg once daily; FZD 600mg twice daily; FZD 800mg once daily

AZT DRUG

Also known as: Zidovudine

AZT twice daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• Provide written or thump printed informed consent prior to all trial-related procedures
• HIV-1 positive with an indication to start antiretroviral therapy (ART) according to WHO and/or country guidelines
• ART naïve, including no history of antiretroviral medication during PMTCT or PEP
• Patient agrees not to take any concomitant medication during the trial without informing the investigator. Traditional medicines should be specified with concomitant medications.
• Availability throughout the study
• 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).
• 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.
• CD4 count ≥100 cells/μl
• Hb ≥9.5 g/dl
• Platelets ≥50,000 cells/mm3
• Neutrophils ≥500 cells/ mm3
• Bilirubin \<2.5 x uln
• ALT \<2.5 x uln
• Creatinine clearance calculated by Cockroft's formula ≥50 ml/min

You may not qualify if:

• 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
• 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.
• HIV-2 infection
• Pregnancy or lactating mother
• Unlikely to comply with protocol as judged by the principal investigator or his designate
• Use of experimental therapeutic agents within 30 days of study entry.
• Hepatitis B with positive HBsAg.

Sponsors & Collaborators

• Michael Hoelscher: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• German Federal Ministry of Education and Research: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• Treichville Academic hospital center, Division of infectious and tropical diseases (SMIT): collaborator
• ANRS, Emerging Infectious Diseases: collaborator
• Kumasi Centre for Collaborative Research (KCCR): collaborator
• Bernhard Nocht Institute for Tropical Medicine: collaborator
• Pharmaceutical Company (Chiracon GmbH): collaborator
• Pharmaceutical Company (STADA Vietnam Joint Venture Co. Ltd.): collaborator

Study Sites (2)

Service des Maladies Infectieuses et Tropicales, CHU de Treichville,

Abidjan, BPV3, Côte d’Ivoire

Location

NIMR - Mbeya Medical Research Programme,

Mbeya, PO Box 2410, Tanzania

Location

MeSH Terms

Interventions

fozivudine tidoxil; Lamivudine; efavirenz; Zidovudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Thymidine

Study Officials

• Michael Hoelscher, Prof.

  Department for Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Leopoldstrasse 5, 80802, Munich, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 26, 2012
• Study Start: December 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: February 1, 2017
• Last Updated: March 7, 2018

Record last verified: 2018-03

Locations

TA (1); CÔ (1)