Trial Outcomes & Findings for Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-naive Participants (NCT NCT00350272)

Last Updated: 2023-08-30

Results Overview

The proportion of participants having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected participants over 12 weeks compared with the proportion of participants having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (\<50 copies/mL) HIV-1 RNA levels from baseline assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

76 participants

Primary outcome timeframe

12 weeks

Results posted on

2023-08-30

Participant Flow

Human immunodeficiency virus (HIV)-1-infected, treatment-naïve adults with no acquired immunodeficiency syndrome (AIDS)-defining events in the 3 months prior to Screening and with plasma HIV-1 ribonucleic acid (RNA) levels greater than or equal to 5000 copies/milliliter (mL) and CD4 counts greater than or equal to 200 cells/microliter (μL) and less than 500 cells/μL, and HIV-1 strains absent of the M184V, M184I, D237E, K103, Y188L, and K65R mutations at Screening.

A total of 78 participants were given a treatment assignment. One participant assigned to treatment was ineligible for randomization and did not receive any study drug. An additional participant did not take any of the dispensed study drug. Therefore, 76 participants were treated.

Participant milestones

Participant milestones
Measure	Elvucitabine, Efavirenz, Tenofovir Elvucitabine (blinded) 10 milligrams (mg)/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Lamivudine, Efavirenz, Tenofovir Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).
Blinded 12-Week Treatment STARTED	39	37
Blinded 12-Week Treatment COMPLETED	30	35
Blinded 12-Week Treatment NOT COMPLETED	9	2
Open-Label 84 Week Treatment STARTED	30	35
Open-Label 84 Week Treatment COMPLETED	21	27
Open-Label 84 Week Treatment NOT COMPLETED	9	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Elvucitabine, Efavirenz, Tenofovir Elvucitabine (blinded) 10 milligrams (mg)/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Lamivudine, Efavirenz, Tenofovir Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).
Blinded 12-Week Treatment Adverse Event	1	0
Blinded 12-Week Treatment Death	1	0
Blinded 12-Week Treatment Lost to Follow-up	2	0
Blinded 12-Week Treatment Withdrawal by Subject	3	0
Blinded 12-Week Treatment Physician Decision	2	1
Blinded 12-Week Treatment Sponsor decision	0	1
Open-Label 84 Week Treatment Adverse Event	2	1
Open-Label 84 Week Treatment Lost to Follow-up	3	2
Open-Label 84 Week Treatment Withdrawal by Subject	1	2
Open-Label 84 Week Treatment Physician Decision	1	2
Open-Label 84 Week Treatment Sponsor decision	2	1

Baseline Characteristics

Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-naive Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elvucitabine n=39 Participants Elvucitabine (blinded) 10 mg/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Lamivudine n=37 Participants Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Total n=76 Participants Total of all reporting groups
Age, Continuous	37.1 years STANDARD_DEVIATION 10.20 • n=5 Participants	36.4 years STANDARD_DEVIATION 11.34 • n=7 Participants	36.6 years STANDARD_DEVIATION 10.71 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	29 Participants n=7 Participants	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	29 Participants n=7 Participants	55 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	21 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Height	68.18 inches STANDARD_DEVIATION 4.433 • n=5 Participants	67.33 inches STANDARD_DEVIATION 4.325 • n=7 Participants	67.77 inches STANDARD_DEVIATION 4.373 • n=5 Participants
Weight	162.03 pounds STANDARD_DEVIATION 41.272 • n=5 Participants	171.37 pounds STANDARD_DEVIATION 52.582 • n=7 Participants	166.58 pounds STANDARD_DEVIATION 47.035 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: This primary outcome measure used the intent-to-treat population, defined as all randomized participants who took at least 1 dose of study drug and had both a baseline HIV-1 RNA result and at least 1 HIV-1 RNA result after baseline assessment. For this analysis, all participants who discontinued from the study before Week 12 were considered as The Noncompleter=Failure (NC=F).

Outcome measures

Outcome measures
Measure	Elvucitabine n=37 Participants Elvucitabine (blinded) 10 mg/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Lamivudine n=37 Participants Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day Week 2	13.5 percentage of participants	8.1 percentage of participants
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day Week 4	16.2 percentage of participants	10.8 percentage of participants
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day Week 10	54.1 percentage of participants	56.8 percentage of participants
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day Week 6	27.0 percentage of participants	35.1 percentage of participants
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day Week 8	35.1 percentage of participants	54.1 percentage of participants
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day Week 12	56.8 percentage of participants	70.3 percentage of participants

PRIMARY outcome

Timeframe: 12 weeks

Population: The analysis population for safety and tolerability was the safety population, defined as all randomized participants who received at least one dose of study drug.

Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events (AEs) and the frequency of Grade 3 and Grade 4 laboratory abnormalities.

Outcome measures

Outcome measures
Measure	Elvucitabine n=39 Participants Elvucitabine (blinded) 10 mg/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Lamivudine n=37 Participants Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).
The Safety Profile Of Elvucitabine. Treatment emergent adverse events	36 participants	35 participants
The Safety Profile Of Elvucitabine. Treatment emergent severe adverse events	3 participants	2 participants
The Safety Profile Of Elvucitabine. Treatment related serious adverse events	0 participants	0 participants
The Safety Profile Of Elvucitabine. Discontinuations due to adverse events	2 participants	0 participants
The Safety Profile Of Elvucitabine. Treatment emergent Grade 3/4 lab abnormalities	6 participants	5 participants

Adverse Events

Elvucitabine

Serious events: 10 serious events

Other events: 37 other events

Deaths: 0 deaths

Lamivudine

Serious events: 5 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Alexion Pharmaceuticals Inc.

Phone: 855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Prior to submitting/presenting a manuscript or materials relating to a Study to a publisher, reviewer, or outside person, the Institution shall provide to Sponsor a copy of all such manuscripts or materials, and Sponsor shall have thirty (30) days to review and comment. The Institution shall, upon Sponsor's request, further delay publication or presentation for a period of up to sixty (60) days to allow Sponsor to protect its interests in any Sponsor Inventions.
Publication restrictions are in place

Restriction type: OTHER

Measure	Elvucitabine n=39 participants at risk Elvucitabine (blinded) 10 mg/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).	Lamivudine n=37 participants at risk Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible participants continued with an additional 84 weeks of open-label treatment (through Week 96).
Blood and lymphatic system disorders Anaemia	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Cardiac disorders Atrial fibrillation	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Gastrointestinal disorders Diverticulum	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Gastrointestinal disorders Enterocutaneous fistula	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Gastrointestinal disorders Oesophagitis	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Appendicitis	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Bronchitis	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Bronchitis acute	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Diverticulitis	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 3 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Influenza	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Pneumonia	5.1% 2/39 • Number of events 2 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Pyelonephritis	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Infections and infestations Tonsillitis	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Injury, poisoning and procedural complications Multiple drug overdose intentional	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Injury, poisoning and procedural complications Upper limb fracture	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/39 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	2.7% 1/37 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Musculoskeletal and connective tissue disorders Fracture nonunion	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Castleman's disease	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Psychiatric disorders Bipolar disorder	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.
Psychiatric disorders Completed suicide	2.6% 1/39 • Number of events 1 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.	0.00% 0/37 • AE data were collected from enrollment into the study to 96 weeks. Treatment-emergent AEs are summarized.