Randomized Study on Multiple Cycles of Interleukin-7 in HIV Patients Immune Non-responders (Inspire 3)

This study has been terminated.
(Terminated [CYTHERISSA filed for banckcuptcy in June 2013.Subjects treated by CYT107 were followed up for at the least 3 months.])
Sponsor:
Information provided by (Responsible Party):
Cytheris SA
ClinicalTrials.gov Identifier:
NCT01241643
First received: November 15, 2010
Last updated: July 24, 2013
Last verified: July 2013
  Purpose

This is a Phase II multicenter, open-labeled, controlled, randomized study assessing weekly doses of Interleukin-7 (CYT107)


Condition Intervention Phase
HIV
Drug: CYT107
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-labeled, Controlled, Randomized Study of Recombinant Interleukin-7 (CYT107) Treatment to Restore and Maintain CD4 T-lymphocyte Counts Above 500 Cells/µL in HIV-infected Patients With CD4 Counts Remaining Between 101-350 Cells/µL After at Least 2 Years of HAART and Plasma HIV RNA < 50 Copies/mL for 18 Months.

Resource links provided by NLM:


Further study details as provided by Cytheris SA:

Primary Outcome Measures:
  • To study the biological activity and safety of repeated cycles of CYT107 at 20 µg/kg/week over 2 weeks, for a maximum of 4 cycles within 21 months and a maximum of 3 cycles within 12 months. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To characterize CYT107 Pharmacokinetics (PK) / Pharmacodynamics (PD) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To characterize the key immuno-pharmacological effects [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • To assess CYT107 effect on HIV-induced chronic systemic immune hyper-activation and its consequences [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 92
Study Start Date: September 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CYT107
repeated cycles of CYT107 at 20 µg/kg/week over 2 weeks, for a maximum of 4 cycles within 21 months and a maximum of 3 cycles within 12 months
Drug: CYT107
repeated cycles of 3 injections of CYT107 at 20 µg/kg/week over 2 weeks, for a maximum of 4 cycles within 21 months and a maximum of 3 cycles within 12 months
No Intervention: Control
Control arm with possible CYT107 injection after 12 months of study participation

Detailed Description:

The aim of the study is to assess repeated cycles of 3 weekly injections of CYT107 in patients immune non-responders infected with HIV.

Eighty patients will be recruited to study the biological activity and safety of repeated cycles of CYT107 at 20 µg/kg/week over 2 weeks, for a maximum of 4 cycles within 21 months and a maximum of 3 cycles within 12 months. The entire study will cover a period of 24 months.

During the study visits the following may be done:

  • medical history, physical examination, blood test every visit
  • EKG
  • chest X-Ray
  • liver/spleen ultrasound
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infection as documented by any licensed ELISA (Enzyme-Linked Immunosorbent Assay) test kit and confirmed either by Western Blot or a 2nd test using a different method at any time prior to study entry
  2. Age ≥18
  3. On HAART (Highly active anti-retroviral therapy) for at least 24 months, on stable regimen for at least 6 months prior to study entry. HAART is defined as a combination of two (2) classes dose regimen of approved ARV (antiretroviral)
  4. CD4+ cell counts ≥ 101 and < 350 cells/µL measured on at least two (2) measurements (including the screening value) within the previous 12 months prior to study entry Note: a single isolated value of CD4+ ≥ 350 during this period (12 months prior to study entry) will be allowed to participate if the previous and subsequent CD4+ count is in the range of ≥ 101 and < 350 cells/µL
  5. Plasma HIV RNA < 50 copies/mL since at least 18 months with at least two (2) measurements (including the screening value) within the previous 6 months prior study entry Note: patients with single blip of detectable viremia during this period (6 months prior to study entry) will be allowed to participate if the prior and subsequent plasma HIV RNA levels are < 50 copies/mL
  6. Adequate bone marrow, hepatic and renal function as follows:

    • Hemoglobin ≥ 10 g/dl
    • Neutrophils ≥ 1,000/µL
    • Platelets ≥ 100,000/µL
    • AST, ALT, or Alk. Phosph. ≤ 2.5 x ULN
    • Total Bilirubin ≤ 1.5 x ULN (or ≤ 5 x ULN if the patient is treated by atazanavir or by indinavir, and if the increase is due to unconjugated bilirubin and if ALT and AST are normal)
    • Lipase ≤ 2 x ULN
    • PT/PTT ≤ 1.5 x ULN
    • Estimated glomerular filtration ≥ 60 ml/min (according to MDRD formula)
  7. Normal blood Thyroid-Stimulating Hormone (TSH)
  8. Ability to understand and sign informed consent

Exclusion Criteria:

  1. AIDS-defining illness (category C) diagnosed within the last 12 months prior to study entry
  2. History of HIV related encephalopathy
  3. Active opportunistic infection including active tuberculosis
  4. Previous treatment with IL-2 or IL-7 at any time prior to study entry
  5. Any planned or probable modification of the anti-retroviral treatment during the first year or the first two cycles of CYT107 Note: in case of product shortage and in absence of viral mutation suspicion or viral blip, a modification of ARV will not be an exclusion criterion
  6. Poor compliance on HAART or any other chronic treatment that in the opinion of the investigator will interfere with protocol participation
  7. Previous treatment with immuno-modulatory agents such as, systemic corticosteroids, growth factors, immunosuppressive drugs, HIV vaccine, or anti-cancer treatment or hydroxyurea within 3 months prior to study entry
  8. 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 Note: Patients with Kaposi's sarcoma limited to the skin that had disappeared while on HAART therapy, and without requiring any other systemic therapy 1 year prior to study entry, will be eligible.
  9. Any history of severe auto-immune disease requiring systemic treatment or hospitalization, or any active auto-immune disease requiring treatment (including multiple sclerosis)
  10. History of splenectomy
  11. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
  12. Chronic hepatitis B or C
  13. HIV-2, HTLV-1 or HTLV-2 seropositivity
  14. Cirrhosis of any origin, and alcoholic or non alcoholic steato-hepatitis, either proven histologically or suspected
  15. Hypertension with a resting systolic blood pressure > 140 or a resting diastolic blood pressure > 90 mm despite adequate antihypertensive treatment
  16. Any cardiac, pulmonary, thyroid, renal, hepatic, gastrointestinal, neurological (central or peripheral) disease requiring therapy and considered as significant by the investigator or a severe disorder of hemostasis
  17. 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 30 days prior to study entry
  18. Pregnant or lactating women. Women of childbearing potential must have a negative serum or urine pregnancy test at study entry
  19. Refusal or inability to practice contraception regardless of the gender of the patient
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241643

Locations
Italy
San Raffaele Scientific Institute
Milano, Italy
South Africa
Helen Joseph Hospital-Themba Lethu Clinic
Johannesbourg, South Africa, 2092
Switzerland
University of Zurich
Zurich, Switzerland, 8091
Sponsors and Collaborators
Cytheris SA
  More Information

No publications provided

Responsible Party: Cytheris SA
ClinicalTrials.gov Identifier: NCT01241643     History of Changes
Other Study ID Numbers: CLI-107-14
Study First Received: November 15, 2010
Last Updated: July 24, 2013
Health Authority: Italy : Fondazione Centro S. Raffale del Monte Tabor
South Africa : MCC

Keywords provided by Cytheris SA:
interleukin-7
immune-based therapies
HIV
infectious disease
immune non-responders

ClinicalTrials.gov processed this record on September 18, 2014