HIV InfectionsPhase 1NCT00477321
Safety Study of IL-7 in HIV-infected Patients (Inspire)
A Phase 1 study testing CYT 107 in people with HIV Infections and Lymphopenia, run by Cytheris SA at 8 sites in 4 countries.
Trial summary
This study will evaluate the safety of a new experimental drug, IL-7, in people with HIV infection. Animal studies have shown that IL-7 can improve the function and number of infection-fighting cells called T lymphocytes, or T cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Lymphopenia
- What is being tested?
- CYT 107
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 8 sitesin 4 countries
- Study dates
- May 2007to Jul 2010
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 18 years
- HIV1 infection as documented by any licensed ELISA test kit and confirmed by Western Blot at anytime prior to study entry.
- On HAART for at least 12 months, and stable on treatment for at least 3 months prior to enrollment. HAART is defined as any protease inhibitor (PI or without ritonavir) + 2 nucleoside reverse transcriptase inhibitors (NNRTI) or any non nucleoside reverse transcriptase inhibitors (NNRTI) + 2 NRTIs. NOTE: RTV-boosted PIs will be considered one antiretroviral drug.
- CD4 cell counts greater than or equal to 101 and less than or equal to 400 cells/mm(3) on at least three consecutive measurements (including the screening value) within the previous 6 months prior to enrollment.
- Patient with CD4 cell counts greater than or equal to 101 and less than or equal to 150 cells/mm(3) with a NADIR greater than or equal to 50 if the NADIR was reached less than 24 months prior to enrollment.
- Plasma HIV RNA less than 50 copies/mL on at least two consecutive measurements (including the screening value) within the previous 6 months prior to enrollment.
Show all 9Show fewer
- No AIDS-defining illness (Category C) within the last 6 months prior to enrollment
- Normal thyroid-stimulating hormone (TSH).
- Ability to understand and give written informed consent.
Who cannot join
- Dual or single antiretroviral therapies with nucleoside analogs.
- Enfuvirtide or any other investigational antiretroviral agent.
- Any planned or probable modification of the antiretroviral treatment during the 3-month study period.
- Current or recent history (less than 30 days prior to screening) of a viral, bacteria, parasitic or fungal infection requiring systemic treatment and/or hospitalization.
- Positive PPD (North American subjects, except those who have received and completed INH prophylaxis).
- Any serious illness requiring systemic treatment and/or hospitalization until the patient either completes therapy or is clinically stable on therapy, in the opinion of the principal investigator, for at least 28 days prior to study entry.
Show all 33Show fewer
- Any history of malignancy (except basal carcinoma of the skin) including any hematologic malignancy or AIDS defining malignancy, such as lymphoproliferative disorder or Kaposi's sarcoma. (Patients with Kaposi's sarcoma limited to the skin that disappeared while on HAART therapy, and without requiring any other systemic therapy, 1 year prior to study entry will be eligible to participate).
- Any history of HIV related encephalopathy.
- Hepatitis B or C (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load or positive anti HCV antibodies with a detectable HCV RNA viral load). Patients who became negative to HBV DNA or HCV RNA following an antiviral treatment should not be enrolled.
- HIV-2, HTLV-1 and HTLV-2 seropositivity.
- Pregnant or lactating women. Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to study entry.
- Refusal or inability to practice contraception during therapy regardless of the gender of the patient.
- Participation in another investigational interventional study during this study or within the last 6 months.
- Family history of sudden cardiac death.
- Corrected QT interval (QTc) prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities.
- Any history of severe auto-immune disease requiring systemic treatment or hospitalization, or any active auto-immune disease requiring treatment.
- Any cardiac, pulmonary, thyroid, renal, hepatic, neurological (central or peripheral) disease requiring therapy and considered as significant by the investigator or a severe disorder of hemostasis.
- Cirrhosis of any origin, and alcoholic or non alcoholic steatohepatitis, either proven histologically or only suspected.
- Any gastrointestinal illness associated with chronic or intermittent diarrhea.
- Hypertension with a resting systolic blood pressure greater than 140 mmHg or a resting diastolic blood pressure greater than 90 mmHg despite adequate antihypertensive treatment.
- Use of tipranavir/ritonavir (TPV/r).
- Previous treatment with IL-2 or IL-7 at any time prior to study entry.
- Prior treatment with immunomodulatory agents such as growth factors, immunosuppressive drugs, cytotoxic chemotherapy or hydroxyurea within 3 months of study entry.
- Use of systemic corticosteroids within 3 months prior to enrollment.
- Any vaccination within 30 days prior to study entry and during the study (until follow-up at W12).
- Need for anticoagulant medication.
- History of splenectomy.
- Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's disease, and autoimmune haemolytic anemia.
- Nephrological abnormalities: Calculated creatinine clearance less than 90 ml/min (according to Cockroft formula) or proteinuria greater than 300 mg/l.
- Other abnormal laboratory findings: hemaglobin less than 10g/dl; Neutrophils less than 1,000/mm(3); Platelets less than 100,000/mm(3); AST, ALT, or Alk. Phosph. greater than 2.5 x ULN; Total bilirubin greater than 1.5 x ULN (or greater than 5 x ULN if the patient is treated by atazanavir or by indinavir, and if the increase is due to unconjugated bilirubin and if liver enzymes are normal); Lipase greater than 2 x ULN; PT/PPT greater than 1.5 x ULN.
- Poor compliance on HAART or any other chronic treatment in the opinion of the investigator.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. Patients must agree to refrain from substance abuse use during the course of the study.
- Any past or current psychiatric illness that, in the opinion of the investigator, would interfere with adherence to study requirements or the ability and willingness to give written informed consent.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States3 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Case Western Reserve University
Cleveland, Ohio, 44106-2602
University of Miami School of Medicine
Miami, Florida, 33136
France3 sites
Hopital Henri Mendor-Service d'Immunologie Clinique
Créteil
Hopital Kremlin Bicêtre
Le Kremlin-Bicêtre
Hopital Saint Louis
Paris
About this study
Official title: A Ph I/IIa Rand Placebo Ctrl, S-Blind Multictr Dose-Esc Study of SC Intermittent Interleukin-7 CYT107 in Chronically HIV-Infected Pts With CD4 T Lymphocyte Counts 101-400 Cells-/mm(3) and Plasma HIV RNA Less Than 50 Copies/mL After at Least 12 M of HAART
This study will evaluate the safety of a new experimental drug, IL-7, in people with HIV infection. Animal studies have shown that IL-7 can improve the function and number of infection-fighting cells called T lymphocytes, or T cells. If this study shows that IL-7 is safe, additional studies will be done to see if it can improve the function or numbers of T-cells in HIV-infected persons.
HIV-infected persons who have been receiving HAART therapy for at least 12 months before enrolling in the study and have been stable on this treatment for at least 3 months before enrollment may be eligible for this study.
Read more
Participants have about 10 clinic visits over 3 months. They receive three injections of IL-7, one injection a week for 3 consecutive weeks. The injections are given as a shot under the skin in the arm or leg. On the day of each injection, the participant stays in the clinic for up to 8 hours or longer for observation and collection of blood samples. Three additional visits (one every 3 months) may be scheduled.
During the study visits the following may be done:
- Medical history, physical examination, blood tests every visit.
- Electrocardiogram (EKG) at study days 0 (day of first dose), 1, 7 (day of second dose), 14 (day of third dose) and 21.
- Chest x-ray study on day 21.
- Blood sample collections at frequent intervals during the first 96 hours after the first dose administration. A catheter (thin plastic tube) may be put into a vein in the arm and left in place to allow several blood samples to be drawn without repeated needle sticks.
- Urine tests several times during the study.
Read the detailed description
Interleukin 7 (IL-7) is an essential cytokine for the thymic development and the post-thymic survival, expansion and maturation of T lymphocytes in humans. The rationale for using IL-7 as immunotherapy in HIV infection would be to support the expansion, survival and functional properties of T lymphocytes and enhance immune reconstitution. Phase I studies of a previous formulation of rhIL7 in cancer and HIV infected patients have shown that T cell proliferation and expansion can be achieved at doses that are well tolerated. The newly glycosylated form of IL-7 tested in this study has a longer half-life allowing weekly administrations.
This is a phase I/IIa, open label, single arm trial that will test the safety of three subcutaneous injections of IL-7 at three different dose levels (10, 20 and 30 micrograms/kilograms) that will be tested sequentially. Eligible subjects (400 cells/microliters greater than CD4 greater than 101 cells/microliters and VL less than 1000 copies/milliliter, on antiretroviral therapy for at least one year) will be given 3 doses of IL-7 at weekly intervals (day 0, day 7 and day 14). Participants will be followed on days 0, 1, 4, 7, 14, 21 and 28 with additional visits on days 35, 56, and 77 and optional follow up every 3 months thereafter until week 56 (approximately 1 year after enrollment). The three doses will be tested sequentially (10, 20 and 30 micrograms/kilograms per dose) and dose escalation will occur only when safety data from day 28 of the previous dose level participants are complete.
Ten subjects will enroll in each dose level and dose escalation will occur only after all subjects complete four weeks without evidence of dose-limiting toxicities. Secondary end points include a PK study of glycosylated rhIL7 as well as immunologic studies throughout the duration of the study to assess evidence of IL7 biologic activity with markers of T cell proliferation and expression of the alpha chain of the IL7 receptor. This is a multi-center international study sponsored by Cytheris with sites in USA, Canada, Italy and France. Children will be excluded and a separate study will be required in the future after the safety and biologic activity of this agent is established in adults. The study will enroll a total of approximately 30 participants.
- Conditions
- HIV Infections, Lymphopenia
- Being tested
- CYT 107
- Keywords
- Interleukin 7, Immune Reconstitution, T Cell Turnover, CD4 Lymphenia, Immune-Based Therapies, HIV Infection
- Medical subject headings
- HIV Infections, Lymphopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYT 107Drug
Also called CYT107, Interleukin-7, rhIL-7
3 dose levels: 3, 10 and 20µg/kg/week.3administrations
| Study group | Role | What they receive |
|---|---|---|
| CYT107 | Experimental | CYT107 vs Placebo (4:1 ratio) Receives: Drug: CYT 107 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Measured: 12 weeks
Secondary outcomes (1)
Changes in T cell counts, changes in T cell proliferation, changes in expression of CD127 on T cells
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2007 (estimated)
- Study startMay 2007
- Primary completionOct 2009
- Study completionJul 2010
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 InfectionsStudies of the same condition, open and under way.
- 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
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytheris SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Lederman, Study chair, Case Western Reserve UniversityYves Levy, Study chair, Hopital Henri MondorIrini Sereti, Study chair, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00477321
- Sponsor's protocol ID
- CLI-107-06
- Status last verified
- Oct 2012
- First submitted
- 22 May 2007
- Last updated
- 18 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stebbing J, Gazzard B, Douek DC. Where does HIV live? N Engl J Med. 2004 Apr 29;350(18):1872-80. doi: 10.1056/NEJMra032395. No abstract available.
PubMed 15115833Battegay M, Nuesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006 May;6(5):280-7. doi: 10.1016/S1473-3099(06)70463-7.
PubMed 16631548Douek DC, Picker LJ, Koup RA. T cell dynamics in HIV-1 infection. Annu Rev Immunol. 2003;21:265-304. doi: 10.1146/annurev.immunol.21.120601.141053. Epub 2001 Dec 19.
PubMed 12524385
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Ph I/IIa Rand Placebo Ctrl, S-Blind Multictr Dose-Esc Study of SC Intermittent Interleukin-7 CYT107 in Chronically HIV-Infected Pts With CD4 T Lymphocyte Counts 101-400 Cells-/mm(3) and Plasma HIV RNA Less Than 50 Copies/mL After at Least 12 M of HAART
- ClinicalTrials.gov ID
- NCT00477321
- Acronym / sponsor ID
- CLI-107-06
- Conditions
- HIV Infections, Lymphopenia
- Keywords
- Interleukin 7, Immune Reconstitution, T Cell Turnover, CD4 Lymphenia, Immune-Based Therapies, HIV Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Cytheris SAIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 23 May 2007 (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 evaluate the safety of a new experimental drug, IL-7, in people with HIV infection. Animal studies have shown that IL-7 can improve the function and number of infection-fighting cells called T lymphocytes, or T cells. If this study shows that IL-7 is safe, additional studies will be done to see if it can improve the function or numbers of T-cells in HIV-infected persons.
HIV-infected persons who have been receiving HAART therapy for at least 12 months before enrolling in the study and have been stable on this treatment for at least 3 months before enrollment may be eligible for this study.
Participants have about 10 clinic visits over 3 months. They receive three injections of IL-7, one injection a week for 3 consecutive weeks. The injections are given as a shot under the skin in the arm or leg. On the day of each injection, the participant stays in the clinic for up to 8 hours or longer for observation and collection of blood samples. Three additional visits (one every 3 months) may be scheduled.
During the study visits the following may be done:
- Medical history, physical examination, blood tests every visit.
- Electrocardiogram (EKG) at study days 0 (day of first dose), 1, 7 (day of second dose), 14 (day of third dose) and 21.
- Chest x-ray study on day 21.
- Blood sample collections at frequent intervals during the first 96 hours after the first dose administration. A catheter (thin plastic tube) may be put into a vein in the arm and left in place to allow several blood samples to be drawn without repeated needle sticks.
- Urine tests several times during the study.
Detailed description
Interleukin 7 (IL-7) is an essential cytokine for the thymic development and the post-thymic survival, expansion and maturation of T lymphocytes in humans. The rationale for using IL-7 as immunotherapy in HIV infection would be to support the expansion, survival and functional properties of T lymphocytes and enhance immune reconstitution. Phase I studies of a previous formulation of rhIL7 in cancer and HIV infected patients have shown that T cell proliferation and expansion can be achieved at doses that are well tolerated. The newly glycosylated form of IL-7 tested in this study has a longer half-life allowing weekly administrations.
This is a phase I/IIa, open label, single arm trial that will test the safety of three subcutaneous injections of IL-7 at three different dose levels (10, 20 and 30 micrograms/kilograms) that will be tested sequentially. Eligible subjects (400 cells/microliters greater than CD4 greater than 101 cells/microliters and VL less than 1000 copies/milliliter, on antiretroviral therapy for at least one year) will be given 3 doses of IL-7 at weekly intervals (day 0, day 7 and day 14). Participants will be followed on days 0, 1, 4, 7, 14, 21 and 28 with additional visits on days 35, 56, and 77 and optional follow up every 3 months thereafter until week 56 (approximately 1 year after enrollment). The three doses will be tested sequentially (10, 20 and 30 micrograms/kilograms per dose) and dose escalation will occur only when safety data from day 28 of the previous dose level participants are complete.
Ten subjects will enroll in each dose level and dose escalation will occur only after all subjects complete four weeks without evidence of dose-limiting toxicities. Secondary end points include a PK study of glycosylated rhIL7 as well as immunologic studies throughout the duration of the study to assess evidence of IL7 biologic activity with markers of T cell proliferation and expression of the alpha chain of the IL7 receptor. This is a multi-center international study sponsored by Cytheris with sites in USA, Canada, Italy and France. Children will be excluded and a separate study will be required in the future after the safety and biologic activity of this agent is established in adults. The study will enroll a total of approximately 30 participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CYT107 | Experimental | Drug: CYT 107CYT107 vs Placebo (4:1 ratio) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
Key exclusion criteria (33 listed)
- Dual or single antiretroviral therapies with nucleoside analogs.
- Enfuvirtide or any other investigational antiretroviral agent.
- Any planned or probable modification of the antiretroviral treatment during the 3-month study period.
- Current or recent history (less than 30 days prior to screening) of a viral, bacteria, parasitic or fungal infection requiring systemic treatment and/or hospitalization.
- Positive PPD (North American subjects, except those who have received and completed INH prophylaxis).
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 |
|---|---|---|
| CYT 107Also: CYT107, Interleukin-7, rhIL-73 dose levels: 3, 10 and 20µg/kg/week.3administrations | Drug | CYT107 |
Primary outcome
Safety
Time frame: 12 weeks
1 secondary outcome
Changes in T cell counts, changes in T cell proliferation, changes in expression of CD127 on T cells
Time frame: 12 weeks
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 18 Oct 2012.
- Background: PubMed 15115833Stebbing J, Gazzard B, Douek DC. Where does HIV live? N Engl J Med. 2004 Apr 29;350(18):1872-80. doi: 10.1056/NEJMra032395. No abstract available.
- Background: PubMed 16631548Battegay M, Nuesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006 May;6(5):280-7. doi: 10.1016/S1473-3099(06)70463-7.
- Background: PubMed 12524385Douek DC, Picker LJ, Koup RA. T cell dynamics in HIV-1 infection. Annu Rev Immunol. 2003;21:265-304. doi: 10.1146/annurev.immunol.21.120601.141053. Epub 2001 Dec 19.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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 Lederman study chair
Case Western Reserve University
Yves Levy study chair
Hopital Henri Mondor
Irini Sereti study chair
National Institute of Allergy and Infectious Diseases (NIAID)
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CYT 107 in people with HIV Infections and Lymphopenia, run by Cytheris SA at 8 sites in 4 countries.
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 9 inclusion and 33 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 18 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, France, Canada, Italy. 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.
What does the primary outcome measure?
Safety (time frame: 12 weeks). 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 NCT00477321, 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 18 Oct 2012.