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

HIV-1 Infection Clinical Trial

— OPTIMAL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01348308
• Other study ID #: 2010-022293-14
• Secondary ID: ANRS 146 OPTIMAL
• Status: Completed
• Phase: Phase 3
• First received: May 2, 2011
• Last updated: July 11, 2016
• Start date: September 2011
• Est. completion date: March 2016

Study information

• Verified date: July 2016
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: The Italian Medicines AgencySpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 407
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• AIDS
• HIV-1 Infection

Intervention

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
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.

Locations

Country	Name	City	State
France	Hôpital Henri Mondor	Creteil

Sponsors (2)

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

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes

External Links

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