HIV InfectionsPhase 2NCT00376935
Effectiveness of Palifermin in Increasing CD4 Counts in Treatment-Experienced HIV Infected Adults
A Phase 2 study testing Palifermin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 22 sites in United States.
Trial summary
Palifermin is a modified version of a naturally occurring human growth factor that is currently approved by the FDA to treat blood cancers. The purpose of this study is to determine whether palifermin can increase CD4 counts in treatment-experienced HIV infected adults. 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?
- Palifermin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 22 sitesUnited States
- Study dates
- Dec 2006to Sep 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 infected
- Receiving potent ART, defined as a combination of three or more antiretroviral drugs for at least 6 months prior to study entry
- CD4 count of 200 cells/mm3 or less within 30 days prior to study entry
- Documented CD4 count obtained at study screening
- Documented current, persistent viral load less than or equal to 200 copies/ml for at least 6 months prior to study entry
- Willing to use acceptable forms of contraception for the duration of the study
Who cannot join
- Active pancreatitis
- Androgens, Immunomodulators (e.g., growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons), or investigational ART within 30 days prior to study entry
- Systemic cancer chemotherapy within 30 days prior to study entry, or history of radiation therapy to the neck and chest regions at any time.
- Allergy or sensitivity to any component of palifermin
- Prior treatment with palifermin or other keratinocyte growth factors
- Current drug or alcohol use that, in the opinion of the investigator, may interfere with study participation
Show all 10Show fewer
- Serious illness or recent surgery that requires systemic treatment or hospitalization. Participants who have completed therapy or are clinically stable on therapy for at least 30 days prior to study entry are not excluded.
- Active cancer
- HIV-1 RNA levels >200 copies/mL within 6 months prior to study entry
- Pregnant or breastfeeding
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308
IHV Baltimore Treatment CRS
Baltimore, Maryland, 21201
Bmc Actg Crs
Boston, Massachusetts, 02118
Unc Aids Crs
Chapel Hill, North Carolina, 27514
Case CRS
Cleveland, Ohio, 44106
MetroHealth CRS
Cleveland, Ohio, 44109
The Ohio State University Medical Center
Columbus, Ohio, 43210
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710
USC CRS
Los Angeles, California, 90033
UCLA CARE Center CRS
Los Angeles, California, 90035
Univ. of Miami AIDS CRS
Miami, Florida, 33136-1013
Vanderbilt Therapeutics CRS
Nashville, Tennessee, 37204
NY Univ. HIV/AIDS CRS
New York, New York, 10016
Columbia P&S CRS
New York, New York, 10032-3732
Stanford CRS
Palo Alto, California, 94304
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
Trillium Health ACTG CRS
Rochester, New York, 14607
Univ. of Rochester ACTG CRS
Rochester, New York, 14642
Ucsd, Avrc Crs
San Diego, California, 92103
University of Washington AIDS CRS
Seattle, Washington, 98104
Washington U CRS
St Louis, Missouri, 63108-2138
Harbor-UCLA Med. Ctr. CRS
Torrance, California, 90502
About this study
Official title: A Double Blind Phase II Study of Multiple Doses of Palifermin (rHuKGF) for the Treatment of Inadequate CD4+ Lymphocyte Recovery in Subjects on Potent Antiretroviral Therapy With Plasma HIV-1 RNA Levels of 200 Copies Per Milliliter or Less
Palifermin is a modified version of a naturally occurring human growth factor that is currently approved by the FDA to treat blood cancers. The purpose of this study is to determine whether palifermin can increase CD4 counts in treatment-experienced HIV infected adults.
Read the detailed description
Antiretroviral therapy (ART) has dramatically improved the clinical outcome for HIV infected adults; however, some people on potent ART experience poor recovery of CD4 counts despite maximum suppression of viral load. Such uncontrolled HIV infection is associated with the reduced ability by the human body to create new T cells (or thymopoiesis). HIV infected adults experiencing reduced thymopoiesis are at increased risk of clinical disease progression.
The thymus is the primary site for CD4 cell development; research suggests that keratinocyte growth factor (KGF) may enhance thymus activity in individuals who exhibit reduced thymopoiesis. Palifermin is a modified version of the naturally occurring KGF that is approved to treat people with hematologic malignancies. The purpose of this study is to evaluate the safety and efficacy of palifermin in increasing CD4 counts, through enhanced thymopoiesis, in treatment-experienced HIV infected adults with suppressed viral loads but low CD4 counts.
This study will last 24 weeks. Participants will be randomly assigned to one of four arms:
- Arm A participants will receive placebo
- Arm B participants will receive palifermin 20 mcg/kg
- Arm C participants will receive palifermin 40 mcg/kg
- Arm D participants will receive palifermin 60 mcg/kg
Participants will receive intravenous doses of their assigned intervention on Days 1, 2, and 3. All participants must remain on their current ART regimen for the duration of the study. ART will not be provided by the study. There will be six study visits, and they will occur at Weeks 1, 2, 4, 8, 12, and 24. All visits will include a targeted physical exam and blood and urine collection.
- Conditions
- HIV Infections
- Being tested
- Palifermin, Palifermin placebo
- Keywords
- Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaliferminDrug
Also called rHuKGF
Keratinocyte growth factor administered via injection
Palifermin placeboDrug
Also called rHuKGF placebo
Keratinocyte growth factor placebo administered via injection
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Participants will receive palifermin placebo injection on Days 1, 2, and 3 Receives: Drug: Palifermin placebo |
| 2 | Experimental | Participants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3 Receives: Drug: Palifermin |
| 3 | Experimental | Participants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3 Receives: Drug: Palifermin |
| 4 | Experimental | Participants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3 Receives: Drug: Palifermin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values)
Median and inter-quartile range of the change in absolute CD4 count from baseline to study week 12 were calculated for each treatment arm. Baseline CD4+ count was defined as the average of pre-entry and entry CD4 count. If one evaluation was missing, the other one was used. If a subject missed a week 12 CD4 count evaluation, then the CD4 count evaluation obtained after starting study treatment and closest in time to week 12 (using the earlier evaluation if necessary to break a tie) was used in place of the missing week 12 evaluation.
Measured: Pre-entry, entry, study week 12
Secondary outcomes (7)
Qualitative Hepatitis C Virus RNA
Measured: At study entry
Grade 3 or 4 Toxicity for Signs and Symptoms From Randomization to Week 24
Number of subjects had a grade 3 or 4 toxicity for signs and symptoms. The toxicity grade scale has the following meaning: 1=mild, 2=moderate, 3=severe, 4=life-threatening.
Measured: From randomization to week 24
Change in Naive CD4+ Cell Counts From Randomization
Measured: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
Change in CT Thymic Index From Randomization
CT thymic index was evaluated at randomization and study week 12, ranging from 0 to 5 whereby 0 means lack of thymic tissue and an organ entirely replaced by fat, 1 means barely recognizable thymic tissue, 2 means minimal soft tissue, 3 means obvious thymic tissue, 4 means moderate thymic tissue, 5 means thymic mass of possible concern for thymoma. Change in CT thymic index from randomization to study week 12 was calculated for participants with both evaluations. The number of participants in each change group was reported by treatment arm.
Measured: randomization, study week 12
Change in Absolute CD4+ Lymphocyte Counts From Randomization to Day 2, Weeks 1, 2, 4, 8, 12, 24.
Measured: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
Grade 3 or 4 Lab Toxicities From Randomization to Week 24
Number of subjects had a grade 3 or 4 toxicity for laboratory abnormalities. The toxicity grade scale has the following meaning: 1=mild, 2=moderate, 3=severe, 4=life-threatening.
Measured: From randomization to study week 24
Number of Death From Randomization to Week 24
Number of subjects died.
Measured: From randomization to week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2006 (estimated)
- Study startDec 2006
- Primary completionJul 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 99 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
- Jeffrey M. Jacobson, MD, Study chair, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376935
- Sponsor's protocol ID
- A5212
- Other IDs
- 10147, ACTG A5212
- Status last verified
- Jan 2019
- First submitted
- 14 Sep 2006
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Aiuti F, Mezzaroma I. Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev. 2006 Apr-Jun;8(2):88-97.
PubMed 16848276Franco JM, Rubio A, Martinez-Moya M, Leal M, Merchante E, Sanchez-Quijano A, Lissen E. T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy. Blood. 2002 May 15;99(10):3702-6. doi: 10.1182/blood.v99.10.3702.
PubMed 11986226van den Brink MR, Alpdogan O, Boyd RL. Strategies to enhance T-cell reconstitution in immunocompromised patients. Nat Rev Immunol. 2004 Nov;4(11):856-67. doi: 10.1038/nri1484.
PubMed 15516965Ye P, Kourtis AP, Kirschner DE. Reconstitution of thymic function in HIV-1 patients treated with highly active antiretroviral therapy. Clin Immunol. 2003 Feb;106(2):95-105. doi: 10.1016/s1521-6616(02)00024-4.
PubMed 12672400
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 Double Blind Phase II Study of Multiple Doses of Palifermin (rHuKGF) for the Treatment of Inadequate CD4+ Lymphocyte Recovery in Subjects on Potent Antiretroviral Therapy With Plasma HIV-1 RNA Levels of 200 Copies Per Milliliter or Less
- ClinicalTrials.gov ID
- NCT00376935
- Acronym / sponsor ID
- A5212
- Conditions
- HIV Infections
- Keywords
- Treatment Experienced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 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
- Dec 2006
- Primary completion
- Jul 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 15 Sep 2006 (estimated)
- Results
- Posted 30 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Palifermin is a modified version of a naturally occurring human growth factor that is currently approved by the FDA to treat blood cancers. The purpose of this study is to determine whether palifermin can increase CD4 counts in treatment-experienced HIV infected adults.
Detailed description
Antiretroviral therapy (ART) has dramatically improved the clinical outcome for HIV infected adults; however, some people on potent ART experience poor recovery of CD4 counts despite maximum suppression of viral load. Such uncontrolled HIV infection is associated with the reduced ability by the human body to create new T cells (or thymopoiesis). HIV infected adults experiencing reduced thymopoiesis are at increased risk of clinical disease progression.
The thymus is the primary site for CD4 cell development; research suggests that keratinocyte growth factor (KGF) may enhance thymus activity in individuals who exhibit reduced thymopoiesis. Palifermin is a modified version of the naturally occurring KGF that is approved to treat people with hematologic malignancies. The purpose of this study is to evaluate the safety and efficacy of palifermin in increasing CD4 counts, through enhanced thymopoiesis, in treatment-experienced HIV infected adults with suppressed viral loads but low CD4 counts.
This study will last 24 weeks. Participants will be randomly assigned to one of four arms:
- Arm A participants will receive placebo
- Arm B participants will receive palifermin 20 mcg/kg
- Arm C participants will receive palifermin 40 mcg/kg
- Arm D participants will receive palifermin 60 mcg/kg
Participants will receive intravenous doses of their assigned intervention on Days 1, 2, and 3. All participants must remain on their current ART regimen for the duration of the study. ART will not be provided by the study. There will be six study visits, and they will occur at Weeks 1, 2, 4, 8, 12, and 24. All visits will include a targeted physical exam and blood and urine collection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Palifermin placeboParticipants will receive palifermin placebo injection on Days 1, 2, and 3 |
| 2 | Experimental | Drug: PaliferminParticipants will receive palifermin 20 mcg/kg injection on Days 1, 2, and 3 |
| 3 | Experimental | Drug: PaliferminParticipants will receive palifermin 40 mcg/kg injection on Days 1, 2, and 3 |
| 4 | Experimental | Drug: PaliferminParticipants will receive palifermin 60 mcg/kg injection on Days 1, 2, and 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- HIV infected
- Receiving potent ART, defined as a combination of three or more antiretroviral drugs for at least 6 months prior to study entry
- CD4 count of 200 cells/mm3 or less within 30 days prior to study entry
- Documented CD4 count obtained at study screening
- Documented current, persistent viral load less than or equal to 200 copies/ml for at least 6 months prior to study entry
Key exclusion criteria (10 listed)
- Active pancreatitis
- Androgens, Immunomodulators (e.g., growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons), or investigational ART within 30 days prior to study entry
- Systemic cancer chemotherapy within 30 days prior to study entry, or history of radiation therapy to the neck and chest regions at any time.
- Allergy or sensitivity to any component of palifermin
- Prior treatment with palifermin or other keratinocyte growth factors
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 |
|---|---|---|
| PaliferminAlso: rHuKGFKeratinocyte growth factor administered via injection | Drug | 2, 3, 4 |
| Palifermin placeboAlso: rHuKGF placeboKeratinocyte growth factor placebo administered via injection | Drug | 1 |
Primary outcome
Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values)
Time frame: Pre-entry, entry, study week 12
Median and inter-quartile range of the change in absolute CD4 count from baseline to study week 12 were calculated for each treatment arm. Baseline CD4+ count was defined as the average of pre-entry and entry CD4 count. If one evaluation was missing, the other one was used. If a subject missed a week 12 CD4 count evaluation, then the CD4 count evaluation obtained after starting study treatment and closest in time to week 12 (using the earlier evaluation if necessary to break a tie) was used in place of the missing week 12 evaluation.
7 secondary outcomes
Qualitative Hepatitis C Virus RNA
Time frame: At study entry
Grade 3 or 4 Toxicity for Signs and Symptoms From Randomization to Week 24
Time frame: From randomization to week 24
Change in Naive CD4+ Cell Counts From Randomization
Time frame: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
Change in CT Thymic Index From Randomization
Time frame: randomization, study week 12
Change in Absolute CD4+ Lymphocyte Counts From Randomization to Day 2, Weeks 1, 2, 4, 8, 12, 24.
Time frame: randomization, day 2, study weeks 1, 2, 4, 8, 12 and 24
Grade 3 or 4 Lab Toxicities From Randomization to Week 24
Time frame: From randomization to study week 24
Number of Death From Randomization to Week 24
Time frame: From randomization to week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16848276Aiuti F, Mezzaroma I. Failure to reconstitute CD4+ T-cells despite suppression of HIV replication under HAART. AIDS Rev. 2006 Apr-Jun;8(2):88-97.
- Background: PubMed 11986226Franco JM, Rubio A, Martinez-Moya M, Leal M, Merchante E, Sanchez-Quijano A, Lissen E. T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy. Blood. 2002 May 15;99(10):3702-6. doi: 10.1182/blood.v99.10.3702.
- Background: PubMed 15516965van den Brink MR, Alpdogan O, Boyd RL. Strategies to enhance T-cell reconstitution in immunocompromised patients. Nat Rev Immunol. 2004 Nov;4(11):856-67. doi: 10.1038/nri1484.
- Background: PubMed 12672400Ye P, Kourtis AP, Kirschner DE. Reconstitution of thymic function in HIV-1 patients treated with highly active antiretroviral therapy. Clin Immunol. 2003 Feb;106(2):95-105. doi: 10.1016/s1521-6616(02)00024-4.
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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.
Jeffrey M. Jacobson, MD study chair
Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine
22 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 Palifermin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 22 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 6 inclusion and 10 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 22 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 30 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Absolute CD4+ Lymphocyte Counts From Baseline (Average of Pre-entry and Entry Values) (time frame: Pre-entry, entry, study week 12). 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 NCT00376935, 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.