Randomized Study on Multiple Cycles of Interleukin-7 in HIV Patients Immune Non-responders

NCT01241643 | Terminated Phase 2 DMC

• 1 other identifier: CLI-107-14
• Study Type: interventional
• Target: 92
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Conditions

HIV

Keywords

interleukin-7; immune-based therapies; HIV; infectious disease; immune non-responders

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (3)

• To characterize CYT107 Pharmacokinetics (PK) / Pharmacodynamics (PD)

  24 months

• To characterize the key immuno-pharmacological effects

  24 months

• To assess CYT107 effect on HIV-induced chronic systemic immune hyper-activation and its consequences

  24 months

Study Arms (2)

CYT107

EXPERIMENTAL

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

Control

NO INTERVENTION

Control arm with possible CYT107 injection after 12 months of study participation

Interventions

CYT107 DRUG

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

CYT107

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age ≥18
• 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)
• 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
• 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
• 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)
• Normal blood Thyroid-Stimulating Hormone (TSH)

You may not qualify if:

• AIDS-defining illness (category C) diagnosed within the last 12 months prior to study entry
• History of HIV related encephalopathy
• Active opportunistic infection including active tuberculosis
• Previous treatment with IL-2 or IL-7 at any time prior to study entry
• Poor compliance on HAART or any other chronic treatment that in the opinion of the investigator will interfere with protocol participation
• 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
• 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.
• Any history of severe auto-immune disease requiring systemic treatment or hospitalization, or any active auto-immune disease requiring treatment (including multiple sclerosis)
• History of splenectomy
• Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
• Chronic hepatitis B or C
• HIV-2, HTLV-1 or HTLV-2 seropositivity
• Cirrhosis of any origin, and alcoholic or non alcoholic steato-hepatitis, either proven histologically or suspected
• Hypertension with a resting systolic blood pressure \> 140 or a resting diastolic blood pressure \> 90 mm despite adequate antihypertensive treatment
• 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

Sponsors & Collaborators

• Cytheris SA: lead

Study Sites (3)

San Raffaele Scientific Institute

Milan, Italy

Location

Helen Joseph Hospital-Themba Lethu Clinic

Johannesburg, 2092, South Africa

Location

University of Zurich

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Thiebaut R, Jarne A, Routy JP, Sereti I, Fischl M, Ive P, Speck RF, D'Offizi G, Casari S, Commenges D, Foulkes S, Natarajan V, Croughs T, Delfraissy JF, Tambussi G, Levy Y, Lederman MM. Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies. Clin Infect Dis. 2016 May 1;62(9):1178-1185. doi: 10.1093/cid/ciw065. Epub 2016 Feb 7.

  PMID: 26908786 DERIVED

MeSH Terms

Conditions

Communicable Diseases

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2010
• First Posted: November 16, 2010
• Study Start: September 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 25, 2013

Record last verified: 2013-07

Locations

CH (1); ZA (1); IT (1)