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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
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: June 23, 2014
Last verified: June 2014
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]

    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


Estimated Enrollment: 408
Study Start Date: September 2011
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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

Contacts
Contact: Yves Levy, MD, PhD 0033149812455 yves.levy@hmn.aphp.fr
Contact: Lydie Beniguel, PhD 0033142164268 lbeniguel@ccde.chups.jussieu.fr

Locations
France
Hôpital Henri Mondor Recruiting
Creteil, France, 94010
Contact: Jean-Daniel Lelievre, MD, PhD         
Principal Investigator: Jean-Daniel Lelievre, MD, PhD         
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

Additional Information:
No publications provided

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: June 23, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Spain: Spanish Agency of Medicines

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:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on August 18, 2014