Safety Study of IL-7 in HIV-infected Patients (Inspire)

Learn more about:
Related Clinical Trial
InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection (Brazil Cohort) Nicotinamide-based Supportive Therapy in Lymphopenia for Patients With COVID-19 Study of Lymphopenia as a Specific Biomarker or Prognostic Risk Factor for Disease Severity in Elderly Patients With COVID-19 InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection ( ILIAD-7-US-I ) InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection ( ILIAD-7-US-O ) InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection FR BL Cohort Etiology of Lymphopenia in Covid19 Infection Donor Stem Cell Boost in Treating Patients With Low Blood Cells After Donor Stem Cell Transplant Pyridostigmine as Immunomodulator in People Living With HIV Regional Differences in Human Immunodeficiency Virus (HIV) Testing Study of Drug to Reduce Thrombocytopenia in Patients Receiving Chemo for Ovarian, Fallopian Tube or Peritoneal Cancer InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort Safety Study of IL-7 in HIV-infected Patients (Inspire) Study of the Effect NT-I7 on CD4 Counts in Patients With High Grade Gliomas Lymphocyte Count as a Sign of Immunoparalysis and Its Correlation With Nutritional Status in Septic Pediatric Patients Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine Models

Brief Title

Safety Study of IL-7 in HIV-infected Patients (Inspire)

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

Brief 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. 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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety

Secondary Outcome

 Changes in T cell counts, changes in T cell proliferation, changes in expression of CD127 on T cells

Condition

HIV Infections

Intervention

CYT 107

Study Arms / Comparison Groups

 CYT107
Description:  CYT107 vs Placebo (4:1 ratio)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

May 2007

Completion Date

July 2010

Primary Completion Date

October 2009

Eligibility Criteria

        -  INCLUSION CRITERIA:

               1. Age greater than or equal to 18 years

               2. HIV1 infection as documented by any licensed ELISA test kit and confirmed by
                  Western Blot at anytime prior to study entry.

               3. 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.

               4. 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.

               5. 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.

               6. 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.

               7. No AIDS-defining illness (Category C) within the last 6 months prior to
                  enrollment

               8. Normal thyroid-stimulating hormone (TSH).

               9. Ability to understand and give written informed consent.

        EXCLUSION CRITERIA:

          1. Dual or single antiretroviral therapies with nucleoside analogs.

          2. Enfuvirtide or any other investigational antiretroviral agent.

          3. Any planned or probable modification of the antiretroviral treatment during the
             3-month study period.

          4. 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.

          5. Positive PPD (North American subjects, except those who have received and completed
             INH prophylaxis).

          6. 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.

          7. 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).

          8. Any history of HIV related encephalopathy.

          9. 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.

         10. HIV-2, HTLV-1 and HTLV-2 seropositivity.

         11. Pregnant or lactating women. Women of childbearing potential must have a negative
             serum or urine pregnancy test within 1 week prior to study entry.

         12. Refusal or inability to practice contraception during therapy regardless of the gender
             of the patient.

         13. Participation in another investigational interventional study during this study or
             within the last 6 months.

         14. Family history of sudden cardiac death.

         15. 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.

         16. Any history of severe auto-immune disease requiring systemic treatment or
             hospitalization, or any active auto-immune disease requiring treatment.

         17. 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.

         18. Cirrhosis of any origin, and alcoholic or non alcoholic steatohepatitis, either proven
             histologically or only suspected.

         19. Any gastrointestinal illness associated with chronic or intermittent diarrhea.

         20. 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.

         21. Use of tipranavir/ritonavir (TPV/r).

         22. Previous treatment with IL-2 or IL-7 at any time prior to study entry.

         23. Prior treatment with immunomodulatory agents such as growth factors, immunosuppressive
             drugs, cytotoxic chemotherapy or hydroxyurea within 3 months of study entry.

         24. Use of systemic corticosteroids within 3 months prior to enrollment.

         25. Any vaccination within 30 days prior to study entry and during the study (until
             follow-up at W12).

         26. Need for anticoagulant medication.

         27. History of splenectomy.

         28. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary
             spherocytosis, Gaucher's disease, and autoimmune haemolytic anemia.

         29. Nephrological abnormalities: Calculated creatinine clearance less than 90 ml/min
             (according to Cockroft formula) or proteinuria greater than 300 mg/l.

         30. 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.

         31. Poor compliance on HAART or any other chronic treatment in the opinion of the
             investigator.

         32. 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.

         33. 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Michael Lederman, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT00477321

Organization ID

CLI-107-06


Responsible Party

Sponsor

Study Sponsor

Cytheris SA


Study Sponsor

Michael Lederman, Study Chair, Case Western Reserve University


Verification Date

October 2012