HIV InfectionsPhase 1/2NCT00089466
Safety and Activity of the Oral HIV Entry Inhibitor AMD11070 in HIV Infected Patients
A Phase 1/2 study testing AMD11070 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
New treatment options are critical for treatment-experienced HIV infected patients with drug resistance. HIV entry inhibitors have been shown effective in patients with resistance to other anti-HIV drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- AMD11070
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2004to Jan 2009
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infected
- Have X4- or dual/mixed-tropic virus confirmed no more than 56 days prior to study entry
- HIV-1 viral load of 5,000 copies/ml or more within 60 days prior to study entry
- If female, willing to discontinue hormonal contraception 1 week prior to study entry
- Willing to use acceptable forms of contraception
Who cannot join
- Antiretroviral treatment within 14 days prior to study entry
- Other prescription medications, herbal supplements, or aspirin within 7 days prior to study entry. Patients taking medication for prophylaxis for Pneumocystis carinii pneumonia (PCP) are not excluded. Patients taking medications approved by protocol officials are not excluded, provided they have been on a stable dose for at least 14 days prior to study entry.
- Nonsteroidal anti-inflammatory drugs (NSAIDS), over the counter medications, or other supplements (including multivitamins) within 1 day prior to study entry
- Heavy exercise within 24 hours before study entry evaluations are done
- Immunizations within 30 days prior to study entry
- Radiation therapy, cytotoxic chemotherapeutic agents, or immunomodulatory agents within 30 days prior to study entry
Show all 14Show fewer
- Current use of some CYP substrates, inhibitors, or inducers. Use of CYP450 substrates is allowed, except for CYP2D6 and CYP2C8 substrates.
- Current use of P-gp inducers or inhibitors
- Allergy or sensitivity to study drug or its formulations
- Active infection or acute illness within 14 days prior to study entry, including HIV-associated opportunistic infections
- History of heart abnormalities. Patients with any repolarization delay (QTc interval of greater than 500 msec) or a history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia) are also excluded.
- Drug or alcohol abuse or dependence or other medical or psychological condition that, in the opinion of the investigator, would interfere with the study or put participants at undue risk
- Chronic diarrhea, defined as having more than 3 stools/day for more than 4 weeks prior to study entry
- Pregnant or breastfeeding
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308
Alabama Therapeutics CRS
Birmingham, Alabama, 35924-2050
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202-5250
About this study
Official title: Phase IB/IIA Dose-Finding Safety and Activity Study of AMD11070 (An Orally Administered CXCR4 Entry Inhibitor) in HIV-Infected Subjects
New treatment options are critical for treatment-experienced HIV infected patients with drug resistance. HIV entry inhibitors have been shown effective in patients with resistance to other anti-HIV drugs. This study will test the safety and anti-HIV activity of eight different doses of the HIV entry inhibitor AMD11070 (also known as AMD070) in HIV infected patients.
Read the detailed description
AMD11070 is an oral HIV-1 entry inhibitor that targets the CXCR4 receptor on T cells. AMD11070 has been shown safe and well-tolerated in Phase I clinical trials in HIV uninfected people. The goal of this study is to evaluate the safety and antiretroviral activity of eight dose levels of AMD11070 in HIV infected adults with X4-tropic virus. Pharmacokinetics (PK) of AMD11070 will also be studied.
This study will last 90 days. All participants will receive medication for 10 days. There are eight cohorts in this study, with a maximum of six participants per cohort. Cohort A will receive 200 mg AMD11070 every 12 hours; Cohort B will receive 400 mg AMD11070 every 12 hours; Cohort C will receive 600 mg AMD11070 every 12 hours; Cohort D will receive 800 mg AMD11070 every 12 hours; Cohort E will receive 1000 mg AMD11070 daily; Cohort F will receive 1500 mg AMD11070 daily; Cohort G will receive 1000 mg AMD11070 every 12 hours; and Cohort H will receive 2000 mg AMD11070 daily. Cohorts B, C, D, and E will open sequentially, provided no more than one of six participants in the preceding cohort experiences dose-limiting toxicity (DLT) based on safety evaluations through Day 17. Cohort G will open to enrollment when Cohort E is filled; Cohort H will open to enrollment when Cohort F is filled. Cohort F will open to enrollment provided no more than one of six participants of Cohorts E and G experiences DLT. All study participants will be offered to receive open-label AMD11070 through a separate long-term safety study.
Participants will either be admitted to the general clinical research center (GCRC) for the dosing period or have dosing, PK testing, and other study monitoring done on an outpatient basis, depending on the study site. Participants admitted to the GCRC for the dosing period will be allowed daytime passes from the GCRC on Days 4, 6, 7, 8, and 9. During the study, participants will have continuous heart monitoring, serial electrocardiograms (EKGs), and vital sign checks. Fasting blood collection will occur on Days 5 and 10. Trough PK testing will occur at entry and on Days 1, 2, 3, 4, 6, 8, and 11. Intensive 24-hour PK testing and 24-hour urine collection will occur on Days 10 and 11. After treatment, targeted physicals and urine collection will occur on Days 17, 30, and 90, and additional blood collection will occur on Days 17, 21, 30, and 90. Participants will undergo an EKG on Days 17 and 90. Participants will also undergo an opthalmologic evaluation and questionnaire sometime after receiving AMD11070.
- Conditions
- HIV Infections
- Being tested
- AMD11070
- Keywords
- Entry Inhibitors, CXCR4 Entry Inhibitors, Treatment Experienced, Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMD11070Drug
AMD11070 taken daily. Dosage dependent on arm.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 200 mg AMD11070 every 12 hours Receives: Drug: AMD11070 |
| B | Experimental | 400 mg AMD11070 every 12 hours Receives: Drug: AMD11070 |
| C | Experimental | 600 mg AMD11070 every 12 hours Receives: Drug: AMD11070 |
| D | Experimental | 800 mg AMD11070 every 12 hours Receives: Drug: AMD11070 |
| E | Experimental | 1000 mg AMD11070 daily Receives: Drug: AMD11070 |
| F | Experimental | 1500 mg AMD11070 daily Receives: Drug: AMD11070 |
| G | Experimental | 1000 mg AMD11070 every 12 hours Receives: Drug: AMD11070 |
| H | Experimental | 2000 mg AMD11070 daily Receives: Drug: AMD11070 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicities of Grade 3 or greater
Measured: during the 10 days of treatment or the 7 days after stopping treatment
Reduction in X4-tropic virus from baseline of 1 log10 relative luciferase units (rlu)
Measured: day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2004 (estimated)
- Study startNov 2004
- Primary completionJun 2006
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Responsible party
- Sponsor
- Investigators
- Michael S. Saag, MD, Study chair, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00089466
- Sponsor's protocol ID
- A5210
- Other IDs
- 10020, ACTG A5210
- Status last verified
- Oct 2012
- First submitted
- 5 Aug 2004
- Last updated
- 9 Nov 2021
- Results posted
- No
Publications
De Clercq E. Emerging anti-HIV drugs. Expert Opin Emerg Drugs. 2005 May;10(2):241-73. doi: 10.1517/14728214.10.2.241.
PubMed 15934866Moore JP, Kitchen SG, Pugach P, Zack JA. The CCR5 and CXCR4 coreceptors--central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 2004 Jan;20(1):111-26. doi: 10.1089/088922204322749567.
PubMed 15000703Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs. 2005;65(13):1747-66. doi: 10.2165/00003495-200565130-00002.
PubMed 16114975Ruibal-Ares BH, Belmonte L, Bare PC, Parodi CM, Massud I, de Bracco MM. HIV-1 infection and chemokine receptor modulation. Curr HIV Res. 2004 Jan;2(1):39-50. doi: 10.2174/1570162043484997.
PubMed 15053339Shaheen F, Collman RG. Co-receptor antagonists as HIV-1 entry inhibitors. Curr Opin Infect Dis. 2004 Feb;17(1):7-16. doi: 10.1097/00001432-200402000-00003.
PubMed 15090884
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB/IIA Dose-Finding Safety and Activity Study of AMD11070 (An Orally Administered CXCR4 Entry Inhibitor) in HIV-Infected Subjects
- ClinicalTrials.gov ID
- NCT00089466
- Acronym / sponsor ID
- A5210
- Conditions
- HIV Infections
- Keywords
- Entry Inhibitors, CXCR4 Entry Inhibitors, Treatment Experienced, Treatment Naive
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Study start
- Nov 2004
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 6 Aug 2004 (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.
New treatment options are critical for treatment-experienced HIV infected patients with drug resistance. HIV entry inhibitors have been shown effective in patients with resistance to other anti-HIV drugs. This study will test the safety and anti-HIV activity of eight different doses of the HIV entry inhibitor AMD11070 (also known as AMD070) in HIV infected patients.
Detailed description
AMD11070 is an oral HIV-1 entry inhibitor that targets the CXCR4 receptor on T cells. AMD11070 has been shown safe and well-tolerated in Phase I clinical trials in HIV uninfected people. The goal of this study is to evaluate the safety and antiretroviral activity of eight dose levels of AMD11070 in HIV infected adults with X4-tropic virus. Pharmacokinetics (PK) of AMD11070 will also be studied.
This study will last 90 days. All participants will receive medication for 10 days. There are eight cohorts in this study, with a maximum of six participants per cohort. Cohort A will receive 200 mg AMD11070 every 12 hours; Cohort B will receive 400 mg AMD11070 every 12 hours; Cohort C will receive 600 mg AMD11070 every 12 hours; Cohort D will receive 800 mg AMD11070 every 12 hours; Cohort E will receive 1000 mg AMD11070 daily; Cohort F will receive 1500 mg AMD11070 daily; Cohort G will receive 1000 mg AMD11070 every 12 hours; and Cohort H will receive 2000 mg AMD11070 daily. Cohorts B, C, D, and E will open sequentially, provided no more than one of six participants in the preceding cohort experiences dose-limiting toxicity (DLT) based on safety evaluations through Day 17. Cohort G will open to enrollment when Cohort E is filled; Cohort H will open to enrollment when Cohort F is filled. Cohort F will open to enrollment provided no more than one of six participants of Cohorts E and G experiences DLT. All study participants will be offered to receive open-label AMD11070 through a separate long-term safety study.
Participants will either be admitted to the general clinical research center (GCRC) for the dosing period or have dosing, PK testing, and other study monitoring done on an outpatient basis, depending on the study site. Participants admitted to the GCRC for the dosing period will be allowed daytime passes from the GCRC on Days 4, 6, 7, 8, and 9. During the study, participants will have continuous heart monitoring, serial electrocardiograms (EKGs), and vital sign checks. Fasting blood collection will occur on Days 5 and 10. Trough PK testing will occur at entry and on Days 1, 2, 3, 4, 6, 8, and 11. Intensive 24-hour PK testing and 24-hour urine collection will occur on Days 10 and 11. After treatment, targeted physicals and urine collection will occur on Days 17, 30, and 90, and additional blood collection will occur on Days 17, 21, 30, and 90. Participants will undergo an EKG on Days 17 and 90. Participants will also undergo an opthalmologic evaluation and questionnaire sometime after receiving AMD11070.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: AMD11070200 mg AMD11070 every 12 hours |
| B | Experimental | Drug: AMD11070400 mg AMD11070 every 12 hours |
| C | Experimental | Drug: AMD11070600 mg AMD11070 every 12 hours |
| D | Experimental | Drug: AMD11070800 mg AMD11070 every 12 hours |
| E | Experimental | Drug: AMD110701000 mg AMD11070 daily |
| F | Experimental | Drug: AMD110701500 mg AMD11070 daily |
| G | Experimental | Drug: AMD110701000 mg AMD11070 every 12 hours |
| H | Experimental | Drug: AMD110702000 mg AMD11070 daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- HIV-1 infected
- Have X4- or dual/mixed-tropic virus confirmed no more than 56 days prior to study entry
- HIV-1 viral load of 5,000 copies/ml or more within 60 days prior to study entry
- If female, willing to discontinue hormonal contraception 1 week prior to study entry
- Willing to use acceptable forms of contraception
Key exclusion criteria (14 listed)
- Antiretroviral treatment within 14 days prior to study entry
- Other prescription medications, herbal supplements, or aspirin within 7 days prior to study entry. Patients taking medication for prophylaxis for Pneumocystis carinii pneumonia (PCP) are not excluded. Patients taking medications approved by protocol officials are not excluded, provided they have been on a stable dose for at least 14 days prior to study entry.
- Nonsteroidal anti-inflammatory drugs (NSAIDS), over the counter medications, or other supplements (including multivitamins) within 1 day prior to study entry
- Heavy exercise within 24 hours before study entry evaluations are done
- Immunizations within 30 days prior to study 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 |
|---|---|---|
| AMD11070AMD11070 taken daily. Dosage dependent on arm. | Drug | A, B, C, D, E, F, G, H |
Primary outcome
Dose-limiting toxicities of Grade 3 or greater
Time frame: during the 10 days of treatment or the 7 days after stopping treatment
Reduction in X4-tropic virus from baseline of 1 log10 relative luciferase units (rlu)
Time frame: day 10
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 9 Nov 2021.
- Background: PubMed 15934866De Clercq E. Emerging anti-HIV drugs. Expert Opin Emerg Drugs. 2005 May;10(2):241-73. doi: 10.1517/14728214.10.2.241.
- Background: PubMed 15000703Moore JP, Kitchen SG, Pugach P, Zack JA. The CCR5 and CXCR4 coreceptors--central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 2004 Jan;20(1):111-26. doi: 10.1089/088922204322749567.
- Background: PubMed 16114975Reeves JD, Piefer AJ. Emerging drug targets for antiretroviral therapy. Drugs. 2005;65(13):1747-66. doi: 10.2165/00003495-200565130-00002.
- Background: PubMed 15053339Ruibal-Ares BH, Belmonte L, Bare PC, Parodi CM, Massud I, de Bracco MM. HIV-1 infection and chemokine receptor modulation. Curr HIV Res. 2004 Jan;2(1):39-50. doi: 10.2174/1570162043484997.
- Background: PubMed 15090884Shaheen F, Collman RG. Co-receptor antagonists as HIV-1 entry inhibitors. Curr Opin Infect Dis. 2004 Feb;17(1):7-16. doi: 10.1097/00001432-200402000-00003.
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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.
Michael S. Saag, MD study chair
University of Alabama at Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AMD11070 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 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 5 inclusion and 14 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 9 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 3 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
What does the primary outcome measure?
Dose-limiting toxicities of Grade 3 or greater (time frame: during the 10 days of treatment or the 7 days after stopping treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00089466, which also lists 5 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 9 Nov 2021.