Clinical Trials

MainTitle

Immuno-stimulation With Maraviroc Combined to Antiretroviral Therapy in Advanced Late Diagnosed HIV-1 Infected Patients (OPTIMAL)

This study has been completed
Sponsor
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Collaborator
Pfizer

Information provided by (Responsible Party)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier
NCT01348308

First received: May 2, 2011
Last updated: July 11, 2016
Last Verified: July 2016
History of Changes
Purpose

Purpose

The objective of the OPTIMAL study is to demonstrate that the adjunction of Maraviroc to a combination of antiretroviral therapy in naive and late diagnosed HIV-1 infected patients counts may accelerate the kinetics of immune restoration and decrease the risk of disease progression and death.

It is a randomized, versus placebo, double-blind trial, conducted in France, Spain and Italy.

Condition Intervention Phase
HIV-1 Infection
AIDS

Drug : Maraviroc (Celsentri)
Drug : Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Optimized Phase III Trial of Immuno-stimulation With Maraviroc, a CCR5 (Chemokine Receptor 5) Antagonist, Combined With Anti Retroviral Therapy in Advanced, Late Diagnosed HIV-1 Infected Patients With an AIDS-defining Event and/or CD4 (Cluster of Differentiation 4) Counts Below 200 Cells/mm³. ANRS 146 OPTIMAL

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures

  • To demonstrate the clinical benefit of the adjunction of Maraviroc to a combination of antiretroviral therapy defined as decrease of clinical events [ Time Frame: From Week 0 to Week 72 ]
    The clinical benefit is the reduction of occurence of a composite outcome consisting of: New AID-defining event (1993 CDC(Centers for Disease Control) expanded surveillance definition) Non B or C events (Aspergillosis, Bartonellosis, Chagas disease, Leishmaniasis, Lymphoma, Microsporidiosis chronic intestinal, Nocardiosis, Penicillium marneffei extrapulmonary, Pneumocystis jiroveci extrapulmonary, Rhodococcus equi disease, Severe bacterial infections) Serious non-AIDS events (Cardiovascular disease, Chronic end stage renal disease, Liver failure, Non-AIDS defining cancers, IRIS) All cause of mortality
Secondary Outcome Measures:
  • Safety evaluation and Clinical, Immunological and pharmacological evaluation [ Time Frame: From Week 0 to Week 72 ]
    The secondary end points: Clinical events (to compare Maraviroc and placebo arm for each component of the primary composite endpoint and other major outcomes) Immunological evaluation (T cells phenotypic analysis; seric markers of immune activation) Virological evaluation (plasma HIV viral load analysis; viral tropism testing,) Pharmacokinetic evaluation (plasma concentration of Maraviroc and relationship with virological response) Clinical and biological safety of the strategy (Adverse events >= grade 2 on ANRS scale of adverse event) Cost-effectiveness analysis

Enrollment: 407
Study Start Date: September 2011
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: Maraviroc
Maraviroc 300, 600 or 1200mg per day
Drug: Maraviroc (Celsentri)
  • Patients will take cART optimized regimen according to the recommended regimen as first line of treatment in most commonly used guidelines with Maraviroc at the following dose: 150 mg orally twice a day for patients receiving a Protease Inhibitor Ritonavir-boosted regimen (except Fosamprenavir), 300 mg orally twice a day for patients receiving a Fosamprenavir Ritonavir-boosted regimen or 600 mg orally twice a day for patients receiving Efavirenz-based regimen.
  • Duration: 72 weeks.

Placebo Comparator: Placebo
Placebo 300, 600 or 1200mg per day
Drug: Placebo
  • Patients will take cART optimized regimen according to the recommended regimen as first line of treatment in most commonly used guidelines with Placebo at the following dose: 150 mg orally twice a day for patients receiving a Protease Inhibitor Ritonavir-boosted regimen (except Fosamprenavir), 300 mg orally twice a day for patients receiving a Fosamprenavir Ritonavir-boosted regimen or 600 mg orally twice a day for patients receiving Efavirenz-based regimen.
  • Duration: 72 weeks.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • Confirmed HIV-1 infection (ELISA and Western Blot tests positive)
  • CD4+ T lymphocytes below or equal 200/mm³ or previous AIDS-defining-illness at diagnosis
  • Patient naïve from any antiretroviral
  • In women, use of a contraceptive method, and lack of actual pregnancy
  • Patients with a coverage from social health
  • After informed consent


Exclusion Criteria:
  • Current pregnancy, lack of contraceptive method, breast-feeding
  • Current active tuberculosis (either suspected, diagnosed)
  • Ongoing malignancies except cutaneous Kaposi's sarcoma. Patients with a previous cancer considered as cured for at least 6 months could be included in the study
  • Current or previous severe cardiac failure, chronic respiratory disease, renal or liver insufficiency; any life-threatening organ failure
  • Cognitive impairment, psychiatric disorders, severe depressive affects, unadapted behavior
  • Use of cytostatic drugs, immunosuppressive agents, steroids
  • PMN (polymorphonuclear neutrophil) below 750/mm³, platelets below 50,000/mm³, haemoglobin below 10 g/dL; ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase) or bilirubin over 2.5 ULN; lipase over 2 ULN (Upper limit of normal), serum creatinine over 1.5 ULN; proteinuria over 1g/L; INR (International Normalized Ratio) abnormal
  • Current or previous, during the 3 last months, use of immunomodulatory agents (G-CSF (granulocyte colony stimulating factor), IL-2 (Interleukin-2), GM-CSF (Granulocyte Macrophage colony stimulating factor), interferons, pentoxifylline)
  • Hypersensitivity to peanut and /or soy products

contacts and locations

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: NCT01348308

Locations

France
Hôpital Henri Mondor
Creteil, France, 94010

Sponsors and Collaborators

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Pfizer

Investigators

Study Chair: Yves Levy, MD, PhD APHP, Hopital Henri Mondor, Creteil, France
Principal Investigator: Jean-Daniel Lelievre, MD, PhD APHP, Hopital Henri Mondor, Creteil, France
Study Director: Dominique Costagliola, PhD INSERM U943 and Univerité Pierre et Marie Curie
More Information

More Information

Additional Information:

Related Info

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)  
ClinicalTrials.gov Identifier: NCT01348308   History of Changes  
Other Study ID Numbers: 2010-022293-14  
  ANRS 146 OPTIMAL  
Study First Received: May 2, 2011  
Last Updated: July 11, 2016  

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Late diagnosed HIV-1 infected patients
AIDS-defining events
Immune restoration

Additional relevant MeSH terms:
Maraviroc

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.