Phase IIIB Study Evaluating the Effects of Atazanavir Powder With Ritonavir in HIV-infected Pediatric Patients

HIV Clinical Trial

— PRINCE2  

Official title:

A Prospective Single Arm, Open-label, International, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Atazanavir (ATV) Powder Boosted With Ritonavir (RTV) With an Optimized NRTI Background Therapy, in Human Immunodeficiency Virus (HIV) Infected, Antiretroviral, Naive and Experienced Pediatric Subjects From 3 Months to Less Than 11 Years.(Pediatric Atazanavir International Clinical Evaluation: the PRINCE II Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01335698
• Other study ID #: AI424-451
• Secondary ID: 2010-024537-23
• Status: Completed
• Phase: Phase 3
• Start date: May 27, 2011
• Est. completion date: January 22, 2018

Study information

• Verified date: October 2018
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to describe the safety, efficacy, and pharmacokinetics of a regimen of atazanavir powder boosted with ritonavir and an optimized dual nucleoside reverse transcriptase inhibitor in pediatric patients aged ≥3 months to <11 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: January 22, 2018
• Est. primary completion date: September 10, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 11 Years

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Key Inclusion Criteria:

• Confirmed HIV-1 infection diagnosed by protocol criteria

• Screening HIV RNA level =1000 copies/mL

• =3 months to <11 years of age at time of first treatment

• Antiretroviral-naive or -experienced

• At screening, all participants must have genotypic sensitivity to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which must be approved for pediatric use at the local country.

• Antiretroviral-experienced patients must also have documented phenotypic sensitivity at screening to atazanavir (Fold Change in susceptibility <2.2) and to at least 2 NRTIs that are approved in their country

Key Exclusion Criteria:

• Experienced participants who received atazanavir or atazanavir/ritonavir at any time prior to study enrollment or who have a history of 2 or more protease inhibitor failures

• Antiretroviral-naïve or -experienced HIV-1-infected patients with contraindication to study medications

• Cardiac rhythm abnormalities

• Need for tenofovir

• Weight <5 or =35kg

• >Grade 2 abnormality in aspartate transaminase/alanine transaminase levels

• Coinfection with either hepatitis B or C virus

• Any active Centers for Disease Control and Prevention Category C clinical condition

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Atazanavir Sulphate

• Ritonavir

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires, Bs As	Buenos Aires
Argentina	Local Institution	Bunos Aires	Buenos Aires
Brazil	Local Institution	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution	Recife	Pernambuco
Brazil	Local Institution	Ribeirao Preto	SAO Paulo
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago	Metropolitana
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Oaxaca
Mexico	Local Institution	Puebla
Poland	Local Institution	Warszawa
Romania	Local Institution	Bucharest
Russian Federation	Local Institution	Smolensk
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St.petersburg
South Africa	Local Institution	Benoni	Gauteng
South Africa	Local Institution	Bloemfontein	FREE State
South Africa	Local Institution	Coronationville	Gauteng
South Africa	Local Institution	Parrow Valley	Western CAPE
South Africa	Local Institution	Port Elizabeth	Eastern CAPE
South Africa	Local Institution	Port Elizabeth	Eastern CAPE
South Africa	Local Institution	Pretoria	Gauteng
South Africa	Local Institution	Soweto	Gauteng
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
United Kingdom	Local Institution	Birmingham	WEST Midlands
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Children'S National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  Mexico,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Died and With Adverse Events (AEs) Leading to Discontinuation, Hyperbilirubinemia, Jaundice, First-degree Arterioventricular Block, Tachycardia, and Rash on ATV Powder	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.	Day one to week 300 (approximately 22-Jan-2018)
Primary	Number of Participants Who Experienced a SAE on ATV Powder	SAE= any of the the following: is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event (defined as a medical event(s) that may not be immediately life threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the subject or may require intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples of such events include, but are not limited to, intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization	Day one to week 300 (approximately 22-Jan-2018)
Primary	Number of Participants With A Center of Disease Control and Prevention (CDC) Class C AIDS Event on ATV Powder	The CDC disease staging system assesses the severity of HIV disease by CD4 cell counts and by the presence of specific HIV-related conditions. CD4 counts are classified as 1: =500 cells/µL, 2: 200-499 cells/µL, and 3: <200 cells/µL. Children with HIV infection are also classified in each of several categories. Category N: Not symptomatic. Category A: Mildly symptomatic. Category B: Moderately symptomatic. Category C: Severely symptomatic.	Day one to week 300 (approximately 22-Jan-2018)
Primary	Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality on ATV Powder	Criteria of the Division of AIDS for grading the severity of adult and pediatric adverse events as follows: Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=potentially life-threatening. Neutrophils (absolute) (adult and infants >7 days): Gr 1=1.000-1300/mm^3; Gr 2=750-999 mm^3; Gr 3=500-749 mm^3; Gr 4= <500 mm^3. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase: Gr 1=1.25-2.5*upper limit of normal (ULN); Gr 2=2.6-5.0*ULN; Gr 3=5.1-10.0*ULN; Gr 4= >10.0*ULN. Bilirubin, total (adults and infants >14 days): Gr 1=1.1-1.5*ULN; Gr 2=1.6-2.5*ULN; Gr 3=2.6-5.0*ULN; Gr 4= >5.0*ULN. Lipase: Gr 1=1.1-1.5*ULN; Gr 2=1.6-3.0*ULN; Gr 3=3.1-5.0*ULN; Gr 4= >5.0*ULN. Bicarbonate, serum low: Gr 1=16.0 mEq/L-	Day one to week 300 (approximately 22-Jan-2018)
Secondary	Number of Participants With HIV RNA <50 Copies/mL and <400 Copies/mL in the Week 24 Atazanavir Powder Cohort and the Eligible Week 48 Atazanavir Powder Cohort	Virologic success includes patients with HIV RNA <50 copies/mL. Two cohorts were assessed: The Atazanavir Powder Cohort=patients who received treatment and did not switch to capsule before analysis Week 24 or before their HIV RNA Week 24 assessment, and the Eligible Week 48 Atazanavir Powder Cohort=patients who initiated study treatment at least 48 weeks before last person last visit and did not switch to capsule before analysis Week 48 or before their HIV RNA Week 48 assessment.	Day 1 of treatment to weeks 24 and 48
Secondary	Mean Change From Baseline in HIV RNA on ATV Powder	Human immunodeficiency virus ribonucleic acid (HIV RNA) change from baseline using observed values	Baseline to Weeks 24 and 48
Secondary	Mean Change From Baseline in CD4 Percent on ATV Powder	Change in CD4 percent using observed values	Baseline to Weeks 24 and 48
Secondary	CD4 Cell Count Changes From Baseline on ATV Powder	CD4 cell count change from baseline using observed values	Baseline to Weeks 24 and 48
Secondary	Number of Participants With Emergent Genotypic Substitutions on ATV Powder Through Week 48	Newly emergent substitutions are on-treatment substitutions that were not detected at baseline.Viral rebound in the resistance analysis was defined as: Less than a 1 log10 drop from baseline in plasma HIV RNA level by Week 16, confirmed by a second plasma HIV RNA level redrawn within 2 and 4 weeks from original sample. Or, a plasma HIV RNA level >200 c/mL after Week 24, confirmed by a second plasma HIV RNA level redrawn within 2 and 4 weeks from original sample. Or, repeated plasma HIV RNA level =50 c/mL after Week 48. Viral rebound was defined as a plasma HIV RNA level =400 c/mL at any time in a patient who had previously achieved a plasma HIV RNA level <50 c/mL. Or, a plasma HIV RNA level =50 c/mL and <1,000 c/mL followed by a return to virologic suppression was considered a viral blip and not a viral rebound. NRTI=nucleoside reverse transcriptase inhibitor	Baseline through Week 48
Secondary	Maximum Observed Plasma Concentration (Cmax)	To describe the PK profile of ATV powder formulation with RTV in pediatric subjects weighing 25 - < 35 kg and/or 6 to < 11 years of age and for the new 5 - < 10 kg cohort (200 mg ATV and 80 mg RTV) in terms of ATV Cmax	Baseline to Week 2
Secondary	Minimum Plasma Concentration (Cmin)	To describe the PK profile of ATV powder formulation with RTV in pediatric subjects weighing 25 - < 35 kg and/or 6 to < 11 years of age and for the new 5 - < 10 kg cohort (200 mg ATV and 80 mg RTV) in terms of ATV Cmin	Baseline to Week 2
Secondary	Area Under the Concentration-Time Curve [AUC(TAU)]	To describe the PK profile of ATV powder formulation with RTV in pediatric subjects weighing 25 - < 35 kg and/or 6 to < 11 years of age and for the new 5 - < 10 kg cohort (200 mg ATV and 80 mg RTV) in terms of ATV AUC	Baseline to Week 2

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