Cytheris initiates Phase I/IIa dose escalation study of patients suffering from ICL

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Oct 15 2009

Cytheris SA, a clinical stage biopharmaceutical company focused on research and development of new therapies for immune modulation, today announced the initiation of a Phase I/IIa dose escalation study of patients suffering from idiopathic CD4 lymphocytopenia (ICL). ICL is a rare, orphan disease characterized by abnormally low CD4 T cell counts without evidence of human immunodeficiency virus (HIV-1 or HIV-2) infection. The trial is a further investigation of Cytheris’ promising investigative immunotherapy, CYT107 (recombinant human interlukin-7, or IL-7), already the subject of six other studies for different indications.

The study is sponsored, conducted and partially funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH). Under the direction of Irini Sereti, M.D., M.H.S., NIAID/NIH Study Investigator, the trial is designed to assess the safety and biological effects of repeated administration of CYT107 and will be conducted at the NIH Clinical Center in Bethesda, Maryland, the largest US hospital devoted entirely to clinical research.

“Since its inception in 1999, Cytheris has had a close relationship with IL-7 investigators at the US National Institutes of Health, a connection that has played a pivotal role in bringing the potential of this cytokine to the attention of the medical community,” said Michel Morre, DVM, President and CEO of Cytheris. ”We are very pleased that NIH has again recognized the value of the IL-7 program and has chosen to provide financial support as well as the participation of NIAID investigators in this clinical development program focused on ICL.”

The trial is called ICICLE (Interleukin-7 (CYT107) Treatment of Idiopathic CD4 Lymphocytopenia: Expansion of CD4 T Cells). It is a Phase I/IIa open-label, single arm clinical trial evaluating the safety profile of glycosylated recombinant human interleukin-7 (rhIL-7) as an immune modulator in patients with ICL at risk of disease progression. Secondary analyses will assess the immunostimulatory effects of rhIL-7 on T cell numbers and function.

"ICL patients have a propensity to develop serious co-morbidities and the dearth of treatment options for their primary lymphocytopenia, particularly in patients who have experienced opportunistic or otherwise serious infections, means that the unmet medical need to establish novel immune treatments for ICL patients persists,” said Thérèse Croughs, MD, Chief Medical Officer of Cytheris. “IL-7 represents a promising investigative therapy which has shown in pre-clinical and Phase I studies in oncology and in HIV-infected patients to be well tolerated in repeated dose trials, with long-lasting increases in both CD4 and CD8 T cells.”

Study Design and Objectives

This is a single center, open-label, single-arm, Phase I/IIa interventional clinical trial. The study population is defined as men and women, aged ≥18 years, with a confirmed diagnosis of ICL (CD4 <300 cells/μL or <20% of lymphocytes on two occasions) deemed at risk for complications due to concurrent CD8 T cell lymphocytopenia and/or a history of opportunistic or otherwise serious infection, without autoimmunity or hematologic or lymphoid malignancy.

Participants will be evaluated at baseline (prior to study treatment) and according to the protocol follow-up schedule, receive a total of 2 cycles of subcutaneous rhIL-7 (CYT107) dosed once weekly for 3 weeks in a dose escalation fashion: 3 μg/kg (first 5 volunteers), 10 μg/kg (next 5 volunteers) and 20 μg/kg (last 5 volunteers), with an additional 5 study participants at the highest achieved dose level. Cycles of rhIL-7 will be administered starting at Week 1 and Week 24.

Approximately 35-40 patients will be screened over a 3-year period to achieve the desired sample of 20 ICL patients. Safety assessments of rhIL-7 will be the primary focus at each study visit, with secondary analyses of immune parameters, including changes from baseline in T cell numbers and function, at Weeks 24 and 48. Enrollment is expected to take 3 to 4 years. Each volunteer will be followed for 48 weeks. Thus, total duration of the study will be approximately 5 years.

The exploratory objectives of this study are to evaluate the immunomodulatory effects of rhIL-7:

Evaluate changes in CD4 and CD8 T cell counts
Evaluate whether any observed changes in CD4 and CD8 T cell counts are due to increasing thymic output and/or peripheral T cell expansion
Evaluate effects on T cell activation status
Evaluate effects on the function and proliferation of antigen-specific T cells
Evaluate effects on gastrointestinal mucosal lymphocytes
Evaluate effects on lymph node-based tissue lymphocytes
Evaluate predictors of response (i.e., increases in CD4 T cells), such as age, baseline total and naïve CD4 T cell counts, baseline CD127 expression on T cells, and MHC haplotype

The restorative effects of exogenous IL-7 on the immune system of ICL patients will be assessed by both flow cytometric immunophenotyping and lymphocyte functional assays to assess the following: