Trial Outcomes & Findings for Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay (NCT NCT00496782)
NCT ID: NCT00496782
Last Updated: 2019-01-30
Results Overview
Spearman's correlation coefficient to assess percentage of participants achieving HIV-1 RNA with tropism
TERMINATED
PHASE1
16 participants
Baseline, Day 4, 7, 14
2019-01-30
Participant Flow
Participant milestones
| Measure |
CCR5-Tropic HIV-1
Subjects treated with maraviroc in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects who had CC chemokine receptor 5 (CCR5) human immunodeficiency virus (HIV) 1 (based on Trofile™ assay) continued receiving maraviroc in combination with a new optimized background therapy (OBT) selected by the investigator until End of Study; Maraviroc was dosed orally twice daily (BID) with the total dose adjusted according to the OBT drugs.
|
Non-CCR5-Tropic HIV-1
Subjects treated with maraviroc (dosed orally twice daily (BID)) in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects with non CCR5 HIV 1 or a non reportable Trofile™ assay at Screening had discontinued maraviroc and had a new OBT selected by the investigator until End of Study.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
7
|
|
Overall Study
COMPLETED
|
8
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
CCR5-Tropic HIV-1
Subjects treated with maraviroc in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects who had CC chemokine receptor 5 (CCR5) human immunodeficiency virus (HIV) 1 (based on Trofile™ assay) continued receiving maraviroc in combination with a new optimized background therapy (OBT) selected by the investigator until End of Study; Maraviroc was dosed orally twice daily (BID) with the total dose adjusted according to the OBT drugs.
|
Non-CCR5-Tropic HIV-1
Subjects treated with maraviroc (dosed orally twice daily (BID)) in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects with non CCR5 HIV 1 or a non reportable Trofile™ assay at Screening had discontinued maraviroc and had a new OBT selected by the investigator until End of Study.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
2
|
Baseline Characteristics
Multicenter Pilot Study To Define The Marker As An Alternate For Tropism Assay
Baseline characteristics by cohort
| Measure |
CCR5-Tropic HIV-1
n=9 Participants
Subjects treated with maraviroc in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects who had CC chemokine receptor 5 (CCR5) human immunodeficiency virus (HIV) 1 (based on Trofile™ assay) continued receiving maraviroc in combination with a new optimized background therapy (OBT) selected by the investigator until End of Study; Maraviroc was dosed orally twice daily (BID) with the total dose adjusted according to the OBT drugs.
|
Non-CCR5-Tropic HIV-1
n=7 Participants
Subjects treated with maraviroc (dosed orally twice daily (BID)) in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects with non CCR5 HIV 1 or a non reportable Trofile™ assay at Screening had discontinued maraviroc and had a new OBT selected by the investigator until End of Study.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.3 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
41.0 years
STANDARD_DEVIATION 4.8 • n=7 Participants
|
44.0 years
STANDARD_DEVIATION 5.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 4, 7, 14Population: Study was canceled: no efficacy data (primary/secondary) was collected per protocol for limited number of patients left in study; only safety data was summarized.
Spearman's correlation coefficient to assess percentage of participants achieving HIV-1 RNA with tropism
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Number of Subjects Achieving HIV-1 RNA \<400 Copies/mL at each time point
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 4, 7, 14, 28, and Weeks 8, 12, 18, and 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Number of Subjects Achieving HIV-1 RNA \<50 Copies/mL at each time point
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA \> 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification \[LOQ\]); 2. Experiencing a \> 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline \> 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA \>1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
For this protocol, virologic failure will be confirmed by a repeat viral load test within 2 weeks of first viral load meeting any of the following criteria: 1. Failing to achieve a reduction in HIV-1 RNA \> 0.5 log10 copies/mL from baseline by the second viral load determination (unless the viral load is below level of quantification \[LOQ\]); 2. Experiencing a \> 0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from baseline \> 0.5 log10 copies/mL; or 3. Experiencing an HIV-1 RNA \>1000 copies/mL after having achieved an HIV-1 RNA below LOQ.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 (Baseline), Day 7, 14, 28 and Weeks 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Calculated average of CD4 at Day 7, 14, 28 and Week 24 minus CD4 at Day 1
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1(Baseline), Day 7, 14, 28 and Weeks 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Calculated average of CD8 at Day 7, 14, 28 and Week 24 minus CD8 at Day 1
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Screening (Day -14 to 0), Day 1.Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Calculated avergae of {CD4 or CD8 at Day 1 - CD4 or CD8 at Screening}
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Screening (Day -21 to 0), Baseline.Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Number of subjects who switch their tropism status from screening to Baseline
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 15 and Week 24/End of Study/DiscontinuationPopulation: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Number of subjects who switch their tropism status from Baseline to Days 7, 14, and Week 24/End of Study(EOS)/Discontinuation
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Screening (Day -21), Baseline (Day 0), Day 14 (after addition of MVC to a failing regimen), Week 24, and time of Virologic Failure.Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Change in detectable resistance (genotype) and susceptibility (phenotype) to drugs in the regimen from Screening
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Screening (Day -21 to 0), Day 14, Week 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Phenotypic susceptibility to maraviroc
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Screening (Day -21 to 0), Day 14, time of virologic failure, and Week 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Change in gene sequence in gp-160, and the V3 loop from Screening visit (Day -21 to 0) to Day 14, time of virologic failure (See Section 6.5.1) and Week 24
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Screening (Day -21 to 0), Day 14, time of virologic failure, Week 24Population: Study was canceled with only 16 subjects of 60 subjects required to enroll.
Outcome measures
Outcome data not reported
Adverse Events
CCR5-Tropic HIV-1
Non-CCR5-Tropic HIV-1
Serious adverse events
| Measure |
CCR5-Tropic HIV-1
n=9 participants at risk
Subjects treated with maraviroc in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects who had CC chemokine receptor 5 (CCR5) human immunodeficiency virus (HIV) 1 (based on Trofile™ assay) continued receiving maraviroc in combination with a new optimized background therapy (OBT) selected by the investigator until End of Study; Maraviroc was dosed orally twice daily (BID) with the total dose adjusted according to the OBT drugs.
|
Non-CCR5-Tropic HIV-1
n=7 participants at risk
Subjects treated with maraviroc (dosed orally twice daily (BID)) in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects with non CCR5 HIV 1 or a non reportable Trofile™ assay at Screening had discontinued maraviroc and had a new OBT selected by the investigator until End of Study.
|
|---|---|---|
|
Cardiac disorders
Myocardial Infarction
|
11.1%
1/9
|
0.00%
0/7
|
|
Infections and infestations
Orchitis
|
11.1%
1/9
|
0.00%
0/7
|
|
Infections and infestations
Pneumonia
|
11.1%
1/9
|
0.00%
0/7
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Testicular neoplasm
|
11.1%
1/9
|
0.00%
0/7
|
|
Nervous system disorders
Headache
|
11.1%
1/9
|
0.00%
0/7
|
|
Nervous system disorders
Syncope
|
11.1%
1/9
|
0.00%
0/7
|
|
Reproductive system and breast disorders
Testicular swelling
|
11.1%
1/9
|
0.00%
0/7
|
Other adverse events
| Measure |
CCR5-Tropic HIV-1
n=9 participants at risk
Subjects treated with maraviroc in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects who had CC chemokine receptor 5 (CCR5) human immunodeficiency virus (HIV) 1 (based on Trofile™ assay) continued receiving maraviroc in combination with a new optimized background therapy (OBT) selected by the investigator until End of Study; Maraviroc was dosed orally twice daily (BID) with the total dose adjusted according to the OBT drugs.
|
Non-CCR5-Tropic HIV-1
n=7 participants at risk
Subjects treated with maraviroc (dosed orally twice daily (BID)) in addition to the antiviral regimen they were receiving at the time of Screening (which was a failing regimen) for 14 days (including Day 14). On Day 15, subjects with non CCR5 HIV 1 or a non reportable Trofile™ assay at Screening had discontinued maraviroc and had a new OBT selected by the investigator until End of Study.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
11.1%
1/9
|
0.00%
0/7
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
1/9
|
14.3%
1/7
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9
|
14.3%
1/7
|
|
Gastrointestinal disorders
Abdominal tenderness
|
11.1%
1/9
|
0.00%
0/7
|
|
Nervous system disorders
Dizziness
|
11.1%
1/9
|
14.3%
1/7
|
|
Nervous system disorders
Neuropathy peripheral
|
22.2%
2/9
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.2%
2/9
|
0.00%
0/7
|
|
Gastrointestinal disorders
Oesophageal disorder
|
11.1%
1/9
|
0.00%
0/7
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9
|
0.00%
0/7
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/9
|
14.3%
1/7
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
1/9
|
0.00%
0/7
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9
|
14.3%
1/7
|
|
General disorders
Injection Site Pain
|
11.1%
1/9
|
0.00%
0/7
|
|
Infections and infestations
Bronchitis
|
11.1%
1/9
|
0.00%
0/7
|
|
Infections and infestations
Otitis Externa
|
0.00%
0/9
|
14.3%
1/7
|
|
Infections and infestations
Staphylococcal Skin Infection
|
11.1%
1/9
|
0.00%
0/7
|
|
Infections and infestations
Tinea Pedis
|
11.1%
1/9
|
0.00%
0/7
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
33.3%
3/9
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
Accidental Overdose
|
11.1%
1/9
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
Contusion
|
11.1%
1/9
|
0.00%
0/7
|
|
Injury, poisoning and procedural complications
Joint Injury
|
0.00%
0/9
|
14.3%
1/7
|
|
Investigations
Hepatic Enzyme Increased
|
11.1%
1/9
|
0.00%
0/7
|
|
Investigations
Human Papilloma Virus Test Positive
|
11.1%
1/9
|
0.00%
0/7
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
11.1%
1/9
|
0.00%
0/7
|
|
Nervous system disorders
Headache
|
22.2%
2/9
|
0.00%
0/7
|
|
Nervous system disorders
Hypoaesthesia
|
11.1%
1/9
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
1/9
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/9
|
14.3%
1/7
|
|
Vascular disorders
Hypertension
|
11.1%
1/9
|
0.00%
0/7
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER