HIV InfectionPhase 1NCT00024986
Tenofovir Disoproxil Fumarate to Treat Pediatric HIV
A Phase 1 study testing Tenofovir DF in people with HIV Infection, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will test the safety, side effects and antiviral activity of different doses of tenofovir DF in children and adolescents with human immunodeficiency virus (HIV) infection. Tenofovir DF belongs to a group of drugs called nucleotide analog reverse transcriptase inhibitors. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infection
- What is being tested?
- Tenofovir DF
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2001to Sep 2005
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV-infected children between the ages of 4 years and less than 18 years.
- BSA greater than or equal to 0.50 (m(2))
- An indication for treatment with antiretrovirals as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (one of the following):
- Clinical symptoms associated with HIV infection (i.e., clinical categories A, B, or C);
- Evidence of immune suppression indicated by CD4 T-lymphocyte count or percentage (i.e., immune category 2 or 3);
- High or increasing HIV RNA copy number;
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- Rapidly declining CD4 T-lymphocyte number or percentage to values approaching those indicative of moderate immune suppression (i.e., immune category 2).
- Children failing at least their second antiretroviral regimen as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (http://www.hivatis.org/) (one of the following):
- Less than a 10-fold decrease from baseline viral load in patients on a HAART regimen (combination regimen that includes a PI and/or NNRTI) after 8-12 weeks of therapy;
- Less than a 5-fold decrease in viral load from baseline in patients on non-HAART regimen (e.g., dual NRTI combinations);
- Viral load not suppressed to undetectable levels after 4-6 months of antiretroviral therapy;
- Repeated detection of HIV RNA in patients who initially responded to antiretroviral therapy with undetectable levels;
- An increase in viral load of greater than 3-fold;
- Change in immunologic classification;
- For children in immunologic category 3, a decline of five percentiles or more in CD4 cell percentage;
- A greater than 30% decline in absolute CD4 cell count;
- Progressive neurodevelopmental deterioration;
- Disease progression;
- Intolerant to or showing evidence of toxicity from other antiretroviral treatments.
- HIV RNA greater than or equal to 10,000 copies/mL within the past 3 months (may be from outside institution);
- Ability to swallow tablets.
- Sexually active patients must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
- Hematologic function: Total WBC greater than 1,500/mm(3), Absolute Neutrophil Count greater than 750/mm(3), hemoglobin greater 8.0 gm/dL and platelet count greater than 75,000/mm(3) at study entry.
- Hepatic function: Liver transaminases must be less than or equal 3.0 times the upper limit of normal; lipase less than 1.5 times the upper limit of normal; Creatinine phosphokinase (CPK) less than 2.5 times the upper limit of normal.
- Renal function: patients must have an age-adjusted normal serum creatinine OR a creatinine clearance greater than or equal to 70 mL/min/1.73.
- Informed Consent: All patients or one of their parents or legal guardians (if the patient is less than 18 years old) must sign the study informed consent to document their understanding of the investigational nature and the risks of the study before any protocol-related studies are performed.
Who cannot join
- Therapeutic regimens including:
- Nephrotoxic agents: aminoglycoside antibiotics, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, oral and IV vancomycin, oral and IV ganciclovir;
- Immunomodulating agents (within 30 days of entry), other than GCSF, erythropoeitin, corticosteroids, IVIG, or anti-D;
- Treatment with chemotherapeutic agents (including hydroxyurea) or radiation therapy within the past 6 weeks; or
- Current use, or use within the last 28 days, of any investigational agent.
- Clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal Investigator or Chairperson would compromise the patient's ability to tolerate this therapy or is likely to interfere with the study procedures or results
- Weight less than 10 kg
- Pregnant or breast feeding females will be excluded from this trial. Women of childbearing potential must be willing to agree to avoid becoming pregnant while on study and for 4 months afterwards.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Study of Tenofovir Disoproxil Fumarate (PMPA Prodrug), A Novel Nucleotide Analog Reverse Transcriptase Inhibitor in Children With HIV Infection
This study will test the safety, side effects and antiviral activity of different doses of tenofovir DF in children and adolescents with human immunodeficiency virus (HIV) infection. Tenofovir DF belongs to a group of drugs called nucleotide analog reverse transcriptase inhibitors. These drugs prevent the virus from replicating (making more copies of itself).
HIV becomes resistant to many drugs used to fight the virus and these drugs become ineffective. In laboratory tests, tenofovir DF has remained effective against HIV longer than other anti-HIV medicines, and when resistance does develop, the virus may still be sensitive to other drugs.
Read more
HIV-infected children between the ages of 4 and 18 years who weigh at least 10 kg (22 pounds) may be eligible for this study. They must be able to receive antiretroviral therapy and have completed at least two previous antiretroviral courses of treatment without benefit.
Upon entering the study, participants will have physical, eye and neuropsychiatric examinations, blood tests, including tests to determine what anti-HIV drugs the patient is resistant to, an echocardiogram (echo), electrocardiogram (EKG), chest X-ray, head CT scan, skin tests, and special tests to examine the bones. These physical exams and tests will be repeated throughout the study to determine changes in health.
Participants will continue their current anti-HIV therapy for 2 weeks and then stop all medicines for a 1-week 'washout' period. After the washout period, patients will begin taking tenofovir DF. For the first 2 days on the drug, a small blood sample (1/2 teaspoon) will be collected 11 times over a 48-hour period through. A heparin lock (a tube kept in place in a vein) may be put in place to avoid multiple needle sticks. Blood samples will be collected for another 4 days to measure how well tenofovir DF alone works against HIV before other drugs are added to the treatment regimen. After these first 6 days, at least two other anti-HIV drugs will be added. They will be selected based on the results of the earlier blood tests for resistance and on the child's medication history.
After 3 days of combination therapy, patients will continue therapy on an outpatient basis. They will be seen in the clinic every 4 weeks at the start of the study and then every 12 weeks for physical exams, lab tests and other procedures as needed. The study will last approximately 48 weeks. Patients who benefit from therapy may be able to continue to receive tenofovir DF from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.
Read the detailed description
This is a pediatric phase I study to determine a biologically active dose and to obtain information concerning the safety, tolerability, and pharmacokinetics of tenofovir disoproxil fumarate (TDF, (9 - [(R)-2[[bis [[isopropoxycarbonyl) oxy] methoxy] phosphinyl] -methoxy]propyl] adenine fumarate (1:1)), formerly known as PMPA prodrug, a potent nucleotide analogue HIV-1 reverse transcriptase (RT) inhibitor, that demonstrates antiviral activity against most NRTI-resistant HIV-1. In addition to obtaining needed biological activity, pediatric safety, tolerability, and pharmacokinetic data, the study will utilize tenofovir DF's potent antiretroviral activity and novel resistance mutation pattern, together with serial measurements of plasma HIV viral load, T-cell flow cytometry, and genotypic and phenotypic viral resistance analysis to conduct pilot studies in pediatric HIV pathogenesis, the response to antiretroviral therapy and to develop strategies to optimize the management of pediatric antiretroviral therapy. We will also use initial viral decay dynamics and other patient characteristics to model prediction for the long-term response to antiretroviral therapy. We will enroll children who have become refractory to or have experienced toxicity on prior antiretroviral therapy. Initial viral genotyping and phenotyping will be performed on the failing regimen, and this data will be used to create the most effective combination regimen with tenofovir DF. After an initial 6 days of tenofovir DF monotherapy, patients will receive tenofovir DF in combination with the optimal antiretroviral therapy as determined by their baseline viral resistance mutation pattern and history. The patients will be followed for at least 96 weeks to assess long-term tolerability and toxicity, and to assess the clinical, virological, and immunological response to tenofovir DF.
- Conditions
- HIV Infection
- Being tested
- Tenofovir DF
- Keywords
- HAART, Genotypic Resistance, Phenotypic Resistance, Immune Reconstitution, Bone Density, HIV, Children, Pediatric HIV Infection
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir DFDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2001 (estimated)
- Study startOct 2001
- Study completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)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
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00024986
- Sponsor's protocol ID
- 020006
- Other IDs
- 02-C-0006
- Status last verified
- Sep 2005
- First submitted
- 10 Oct 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Palumbo PE, Raskino C, Fiscus S, Pahwa S, Fowler MG, Spector SA, Englund JA, Baker CJ. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA. 1998 Mar 11;279(10):756-61. doi: 10.1001/jama.279.10.756.
PubMed 9508151Parkin NT, Lie YS, Hellmann N, Markowitz M, Bonhoeffer S, Ho DD, Petropoulos CJ. Phenotypic changes in drug susceptibility associated with failure of human immunodeficiency virus type 1 (HIV-1) triple combination therapy. J Infect Dis. 1999 Sep;180(3):865-70. doi: 10.1086/314928.
PubMed 10438382Deeks SG, Hellmann NS, Grant RM, Parkin NT, Petropoulos CJ, Becker M, Symonds W, Chesney M, Volberding PA. Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome. J Infect Dis. 1999 Jun;179(6):1375-81. doi: 10.1086/314775.
PubMed 10228057
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Tenofovir Disoproxil Fumarate (PMPA Prodrug), A Novel Nucleotide Analog Reverse Transcriptase Inhibitor in Children With HIV Infection
- ClinicalTrials.gov ID
- NCT00024986
- Acronym / sponsor ID
- 020006
- Conditions
- HIV Infection
- Keywords
- HAART, Genotypic Resistance, Phenotypic Resistance, Immune Reconstitution, Bone Density, HIV, Children, Pediatric HIV Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2001
- Study completion
- Sep 2005
- First posted
- 11 Oct 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.
This study will test the safety, side effects and antiviral activity of different doses of tenofovir DF in children and adolescents with human immunodeficiency virus (HIV) infection. Tenofovir DF belongs to a group of drugs called nucleotide analog reverse transcriptase inhibitors. These drugs prevent the virus from replicating (making more copies of itself).
HIV becomes resistant to many drugs used to fight the virus and these drugs become ineffective. In laboratory tests, tenofovir DF has remained effective against HIV longer than other anti-HIV medicines, and when resistance does develop, the virus may still be sensitive to other drugs.
HIV-infected children between the ages of 4 and 18 years who weigh at least 10 kg (22 pounds) may be eligible for this study. They must be able to receive antiretroviral therapy and have completed at least two previous antiretroviral courses of treatment without benefit.
Upon entering the study, participants will have physical, eye and neuropsychiatric examinations, blood tests, including tests to determine what anti-HIV drugs the patient is resistant to, an echocardiogram (echo), electrocardiogram (EKG), chest X-ray, head CT scan, skin tests, and special tests to examine the bones. These physical exams and tests will be repeated throughout the study to determine changes in health.
Participants will continue their current anti-HIV therapy for 2 weeks and then stop all medicines for a 1-week 'washout' period. After the washout period, patients will begin taking tenofovir DF. For the first 2 days on the drug, a small blood sample (1/2 teaspoon) will be collected 11 times over a 48-hour period through. A heparin lock (a tube kept in place in a vein) may be put in place to avoid multiple needle sticks. Blood samples will be collected for another 4 days to measure how well tenofovir DF alone works against HIV before other drugs are added to the treatment regimen. After these first 6 days, at least two other anti-HIV drugs will be added. They will be selected based on the results of the earlier blood tests for resistance and on the child's medication history.
After 3 days of combination therapy, patients will continue therapy on an outpatient basis. They will be seen in the clinic every 4 weeks at the start of the study and then every 12 weeks for physical exams, lab tests and other procedures as needed. The study will last approximately 48 weeks. Patients who benefit from therapy may be able to continue to receive tenofovir DF from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.
Detailed description
This is a pediatric phase I study to determine a biologically active dose and to obtain information concerning the safety, tolerability, and pharmacokinetics of tenofovir disoproxil fumarate (TDF, (9 - [(R)-2[[bis [[isopropoxycarbonyl) oxy] methoxy] phosphinyl] -methoxy]propyl] adenine fumarate (1:1)), formerly known as PMPA prodrug, a potent nucleotide analogue HIV-1 reverse transcriptase (RT) inhibitor, that demonstrates antiviral activity against most NRTI-resistant HIV-1. In addition to obtaining needed biological activity, pediatric safety, tolerability, and pharmacokinetic data, the study will utilize tenofovir DF's potent antiretroviral activity and novel resistance mutation pattern, together with serial measurements of plasma HIV viral load, T-cell flow cytometry, and genotypic and phenotypic viral resistance analysis to conduct pilot studies in pediatric HIV pathogenesis, the response to antiretroviral therapy and to develop strategies to optimize the management of pediatric antiretroviral therapy. We will also use initial viral decay dynamics and other patient characteristics to model prediction for the long-term response to antiretroviral therapy. We will enroll children who have become refractory to or have experienced toxicity on prior antiretroviral therapy. Initial viral genotyping and phenotyping will be performed on the failing regimen, and this data will be used to create the most effective combination regimen with tenofovir DF. After an initial 6 days of tenofovir DF monotherapy, patients will receive tenofovir DF in combination with the optimal antiretroviral therapy as determined by their baseline viral resistance mutation pattern and history. The patients will be followed for at least 96 weeks to assess long-term tolerability and toxicity, and to assess the clinical, virological, and immunological response to tenofovir DF.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (26 listed)
- HIV-infected children between the ages of 4 years and less than 18 years.
- BSA greater than or equal to 0.50 (m(2))
- An indication for treatment with antiretrovirals as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (one of the following):
- Clinical symptoms associated with HIV infection (i.e., clinical categories A, B, or C);
- Evidence of immune suppression indicated by CD4 T-lymphocyte count or percentage (i.e., immune category 2 or 3);
Key exclusion criteria (8 listed)
- Nephrotoxic agents: aminoglycoside antibiotics, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, oral and IV vancomycin, oral and IV ganciclovir;
- Immunomodulating agents (within 30 days of entry), other than GCSF, erythropoeitin, corticosteroids, IVIG, or anti-D;
- Treatment with chemotherapeutic agents (including hydroxyurea) or radiation therapy within the past 6 weeks; or
- Current use, or use within the last 28 days, of any investigational agent.
- Clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal Investigator or Chairperson would compromise the patient's ability to tolerate this therapy or is likely to interfere with the study procedures or results
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 |
|---|---|---|
| Tenofovir DF | 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 Mar 2008.
- Background: PubMed 9508151Palumbo PE, Raskino C, Fiscus S, Pahwa S, Fowler MG, Spector SA, Englund JA, Baker CJ. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA. 1998 Mar 11;279(10):756-61. doi: 10.1001/jama.279.10.756.
- Background: PubMed 10438382Parkin NT, Lie YS, Hellmann N, Markowitz M, Bonhoeffer S, Ho DD, Petropoulos CJ. Phenotypic changes in drug susceptibility associated with failure of human immunodeficiency virus type 1 (HIV-1) triple combination therapy. J Infect Dis. 1999 Sep;180(3):865-70. doi: 10.1086/314928.
- Background: PubMed 10228057Deeks SG, Hellmann NS, Grant RM, Parkin NT, Petropoulos CJ, Becker M, Symonds W, Chesney M, Volberding PA. Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome. J Infect Dis. 1999 Jun;179(6):1375-81. doi: 10.1086/314775.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tenofovir DF in people with HIV Infection, run by National Cancer Institute (NCI) at 1 site 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 26 inclusion and 8 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 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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 NCT00024986, which also lists 3 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 Mar 2008.