HIV InfectionsPhase 2NCT00001085
A Study of 141W94 Used Alone or in Combination With Zidovudine Plus 3TC in HIV-Infected Patients
A Phase 2 study testing Amprenavir, Lamivudine and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
Trial summary
To determine the proportion of patients whose plasma HIV-1 RNA level remains below a detectable level (less than 500/ml) after 24 weeks of study therapy with either 141W94 monotherapy or 141W94 plus zidovudine (ZDV) and lamivudine (3TC). Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Amprenavir, Lamivudine and Zidovudine
- How many people
- 94 participants
- Where
- 15 sitesUnited States
- Study dates
- Start not givento Sep 1998
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Chemoprophylaxis for Pneumocystis carinii pneumonia is required for all patients who have a CD4 cell count <= 200 cells/mm3.
- Topical and/or oral antifungal agents, except for those listed in excluded medications.
- Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated, unless listed in excluded medications.
- All antibiotics as clinically indicated.
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- Systemic corticosteroid use for <= 21 days for acute problems is permitted as medically indicated; chronic systemic corticosteroid use is not permitted.
- Recombinant erythropoietin and granulocyte colony-stimulating factor as medically indicated.
- Regularly prescribed medications such as:
- antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (a barrier method is also required for this study), megestrol acetate, testosterone or any other medications, as medically indicated.
- Alternative therapies such as vitamins, acupuncture and visualization techniques are permitted (excluding herbal medications).
- NOTE:
- Patients should report the use of these therapies; alternative therapies will be recorded.
- Patients must have:
- HIV-1 infection as documented by ELISA and confirmed.
- >= 5,000 HIV-1 RNA copies/ml (within 30 days prior to study entry).
- CD4 cell count >= 50 cells/mm3 within 60 days prior to study entry.
- Signed, informed consent for patients < 18 years of age.
- Prior Medication: Required:
- Patients must be on a stable antiretroviral regimen for 30 days prior to study screening and remain on the same regimen until entry.
Who cannot join
- Co-existing Condition:
- Patients with the following symptoms or conditions are excluded:
- Any active infection requiring acute treatment within 14 days prior to entry.
- A malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.
- NOTE:
- Patients with minimal Kaposi's sarcoma, defined as <= 5 cutaneous lesions and no visceral disease or tumor-associated edema, will be allowed to enroll as long as they do not require systemic therapy for Kaposi's sarcoma.
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- Patients with the following prior symptoms and conditions are excluded:
- Inability to tolerate ZDV 500-600 mg daily if ZDV was administered previously. Intolerance to ZDV is defined as any grade toxicity that resulted in a dose reduction or termination of ZDV.
- Prior Medication:
- Excluded:
- Any 3TC therapy prior to entry.
- Any HIV-1 protease inhibitor therapy prior to study entry (e.g., saquinavir, ritonavir, indinavir, nelfinavir, 141W94).
- Any immunomodulator therapy within 30 days prior to entry.
- Active immunization within 30 days prior to entry.
- Any antiretroviral therapy change within 30 days prior to study screening.
- 1. Concurrent use of non-protocol specified antiretroviral agents; either investigational or licensed.
- Immunomodulators that affect immunologic or virologic indices such as systemic corticosteroids, thalidomide, or cytokines.
- Concomitant use of rifabutin and/or rifampin.
- Investigational drugs other than 141W94/VX-478.
- Systemic cytotoxic chemotherapy.
- Oral astemizole (Hismanal), carbamazepine (Tegretol), dexamethasone (Decadron), ketoconazole (Nizoral), itraconazole (Sporanox), phenobarbital, phenytoin (Dilantin), terfenadine (Seldane), cisapride (Propulsid), triazolam (Halcion) and midazolam (Versed).
- Herbal medications.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308
University of Colorado Hospital CRS
Aurora, Colorado, 80262
Alabama Therapeutics CRS
Birmingham, Alabama, 35294
Bmc Actg Crs
Boston, Massachusetts, 02118
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215
Unc Aids Crs
Chapel Hill, North Carolina, 275997215
Northwestern University CRS
Chicago, Illinois, 60611
Cook County Hosp. CORE Ctr.
Chicago, Illinois, 60612
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612
USC CRS
Los Angeles, California, 900331079
Univ. of Miami AIDS CRS
Miami, Florida, 331361013
NY Univ. HIV/AIDS CRS
New York, New York, 10016
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, 63112
Washington U CRS
St Louis, Missouri
About this study
Official title: A Randomized, Double-Blind, Phase II Study of 141W94 (VX-478) Monotherapy vs. 141W94 (VX-478) Plus ZDV Plus 3TC in HIV Infected Individuals
To determine the proportion of patients whose plasma HIV-1 RNA level remains below a detectable level (less than 500/ml) after 24 weeks of study therapy with either 141W94 monotherapy or 141W94 plus zidovudine (ZDV) and lamivudine (3TC). To determine the safety and tolerability of 141W94 monotherapy and the combination of 141W94 plus 3TC in patients with HIV infection.
Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.
Read the detailed description
Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.
In this randomized, double-blind study, patients' HIV RNA is screened 30 days prior to entry. Patients satisfying enrollment criteria must have been on a stable antiretroviral regimen for 30 days prior to study screening and remain on the same regimen until entry. Patients are stratified based on the screening HIV-1 RNA copy number obtained within 30 days of entry: 5,000 - 50,000 copies/ml versus greater than 50,000 copies/ml. In addition, patients are stratified based on previous antiretroviral use: naive versus experienced. Patients are randomized to one of 2 treatment arms: Arm A - 141W94, plus Zidovudine (ZDV) and Lamivudine (3TC) or Arm B - 141W94, plus ZDV placebo and 3TC placebo.
[AS PER AMENDMENT 8/25/97: Patients assigned to the monotherapy arm are advised to discontinue their study medication immediately and initiate antiretroviral therapy with indinavir, nevirapine, stavudine and 3TC, as outlined in ACTG 347 roll-over protocol, ACTG 373. Patients in the three-drug arm continue on study therapy.] [AS PER AMENDMENT 12/19/97: Patients receive study treatment for 56 weeks and are followed through week 68.]
- Conditions
- HIV Infections
- Being tested
- Amprenavir, Lamivudine, Zidovudine
- Keywords
- HIV-1, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, HIV Protease Inhibitors, Lamivudine, RNA, Viral, VX 478, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Viral Load
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmprenavirDrug
LamivudineDrug
ZidovudineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionSep 1998
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 94 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Murphy R, Study chairGulick R, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001085
- Sponsor's protocol ID
- ACTG 347
- Other IDs
- 11317
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Murphy RL, Gulick RM, DeGruttola V, D'Aquila RT, Eron JJ, Sommadossi JP, Currier JS, Smeaton L, Frank I, Caliendo AM, Gerber JG, Tung R, Kuritzkes DR. Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection. AIDS Clinical Trials Group 347 Study Team. J Infect Dis. 1999 Apr;179(4):808-16. doi: 10.1086/314668.
PubMed 10068575Murphy R, Degruttola V, Gulick R, D'Aquila R, Eron J, Sommadossi JP, Smeaton L, Currier J, Tung R, Kuritzkes D. 141W94 with or without zidovudine/3TC in patients with no prior protease inhibitor or 3TC therapy-ACTG 347. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:175 (abstract no 512)
Eron JJ Jr, Smeaton LM, Fiscus SA, Gulick RM, Currier JS, Lennox JL, D'Aquila RT, Rogers MD, Tung R, Murphy RL. The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). J Infect Dis. 2000 May;181(5):1622-8. doi: 10.1086/315447. Epub 2000 Apr 26.
PubMed 10783117Eron J, Smeaton L, Degruttola V, Schock J, Fiscus S, Tung R, Gulick R, Murphy R. The effects of amprenavir (APV) alone or in combination with ZDV/3TC, on HIV-1 levels in semen: a substudy of ACTG 347. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:109 (abstract no 222)
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Phase II Study of 141W94 (VX-478) Monotherapy vs. 141W94 (VX-478) Plus ZDV Plus 3TC in HIV Infected Individuals
- ClinicalTrials.gov ID
- NCT00001085
- Acronym / sponsor ID
- ACTG 347
- Conditions
- HIV Infections
- Keywords
- HIV-1, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, HIV Protease Inhibitors, Lamivudine, RNA, Viral, VX 478
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Sep 1998 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the proportion of patients whose plasma HIV-1 RNA level remains below a detectable level (less than 500/ml) after 24 weeks of study therapy with either 141W94 monotherapy or 141W94 plus zidovudine (ZDV) and lamivudine (3TC). To determine the safety and tolerability of 141W94 monotherapy and the combination of 141W94 plus 3TC in patients with HIV infection.
Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.
Detailed description
Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.
In this randomized, double-blind study, patients' HIV RNA is screened 30 days prior to entry. Patients satisfying enrollment criteria must have been on a stable antiretroviral regimen for 30 days prior to study screening and remain on the same regimen until entry. Patients are stratified based on the screening HIV-1 RNA copy number obtained within 30 days of entry: 5,000 - 50,000 copies/ml versus greater than 50,000 copies/ml. In addition, patients are stratified based on previous antiretroviral use: naive versus experienced. Patients are randomized to one of 2 treatment arms: Arm A - 141W94, plus Zidovudine (ZDV) and Lamivudine (3TC) or Arm B - 141W94, plus ZDV placebo and 3TC placebo.
[AS PER AMENDMENT 8/25/97: Patients assigned to the monotherapy arm are advised to discontinue their study medication immediately and initiate antiretroviral therapy with indinavir, nevirapine, stavudine and 3TC, as outlined in ACTG 347 roll-over protocol, ACTG 373. Patients in the three-drug arm continue on study therapy.] [AS PER AMENDMENT 12/19/97: Patients receive study treatment for 56 weeks and are followed through week 68.]
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- Chemoprophylaxis for Pneumocystis carinii pneumonia is required for all patients who have a CD4 cell count <= 200 cells/mm3.
- Topical and/or oral antifungal agents, except for those listed in excluded medications.
- Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated, unless listed in excluded medications.
- All antibiotics as clinically indicated.
- Systemic corticosteroid use for <= 21 days for acute problems is permitted as medically indicated; chronic systemic corticosteroid use is not permitted.
Key exclusion criteria (22 listed)
- Any active infection requiring acute treatment within 14 days prior to entry.
- A malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.
- Patients with minimal Kaposi's sarcoma, defined as <= 5 cutaneous lesions and no visceral disease or tumor-associated edema, will be allowed to enroll as long as they do not require systemic therapy for Kaposi's sarcoma.
- Inability to tolerate ZDV 500-600 mg daily if ZDV was administered previously. Intolerance to ZDV is defined as any grade toxicity that resulted in a dose reduction or termination of ZDV.
- Any 3TC therapy prior to entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amprenavir | Drug | – |
| Lamivudine | Drug | – |
| Zidovudine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Background: PubMed 10068575Murphy RL, Gulick RM, DeGruttola V, D'Aquila RT, Eron JJ, Sommadossi JP, Currier JS, Smeaton L, Frank I, Caliendo AM, Gerber JG, Tung R, Kuritzkes DR. Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection. AIDS Clinical Trials Group 347 Study Team. J Infect Dis. 1999 Apr;179(4):808-16. doi: 10.1086/314668.
- BackgroundMurphy R, Degruttola V, Gulick R, D'Aquila R, Eron J, Sommadossi JP, Smeaton L, Currier J, Tung R, Kuritzkes D. 141W94 with or without zidovudine/3TC in patients with no prior protease inhibitor or 3TC therapy-ACTG 347. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:175 (abstract no 512)
- Background: PubMed 10783117Eron JJ Jr, Smeaton LM, Fiscus SA, Gulick RM, Currier JS, Lennox JL, D'Aquila RT, Rogers MD, Tung R, Murphy RL. The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). J Infect Dis. 2000 May;181(5):1622-8. doi: 10.1086/315447. Epub 2000 Apr 26.
- BackgroundEron J, Smeaton L, Degruttola V, Schock J, Fiscus S, Tung R, Gulick R, Murphy R. The effects of amprenavir (APV) alone or in combination with ZDV/3TC, on HIV-1 levels in semen: a substudy of ACTG 347. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:109 (abstract no 222)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Murphy R study chair
Gulick R study chair
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amprenavir, Lamivudine and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001085, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.