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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection; AIDS
• Intervention / Treatment: Drug: Maraviroc (Celsentri); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Hopital Henri Mondor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To demonstrate the clinical benefit of the adjunction of Maraviroc to a combination of antiretroviral therapy defined as decrease of clinical events	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	From Week 0 to Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation and Clinical, Immunological and pharmacological evaluation	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	From Week 0 to Week 72

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: 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

Publications and helpful links

General Publications

• Levy Y, Lelievre JD, Assoumou L, Aznar E, Pulido F, Tambussi G, Crespo M, Meybeck A, Molina JM, Delaugerre C, Izopet J, Peytavin G, Cardon F, Diallo A, Lancar R, Beniguel L, Costagliola D. Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial. Ann Intern Med. 2020 Mar 3;172(5):297-305. doi: 10.7326/M19-2133. Epub 2020 Feb 11.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 2, 2011
• First Submitted That Met QC Criteria: May 4, 2011
• First Posted (Estimate): May 5, 2011

Study Record Updates

• Last Update Posted (Estimate): July 12, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Late diagnosed HIV-1 infected patients; AIDS-defining events; Immune restoration
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: 2010-022293-14; ANRS 146 OPTIMAL