AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis

Systemic Sclerosis Clinical Trial

Official title: A Double-Blind Placebo-Controlled Pilot Study of Safety and Tolerability of AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis

Status Active, not recruiting

Clinical Trial Summary

To study the safety and tolerability of a hyperimmune goat serum product (AIMSPRO) in the treatment of systemic sclerosis (SSc) through a period of 26 weeks of study participation. The secondary objective of the study is to assess the efficacy of AIMSPRO as a therapeutic agent for SSc using inter alia the SSc-HAQ questionnaire and the modified Rodnan skin score.

Clinical Trial Description

Systemic sclerosis (scleroderma, SSc) is a multisystemic disease clinically characterized by fibrosis of the skin, joints, muscles and internal organs. Systemic sclerosis is a rare disease, with an estimated incidence of 19 individuals per million population per year.

The pathogenesis of SSc remains incompletely understood although it seems likely that there is an interplay between inflammatory, vascular and fibroblast dysfunction, leading ultimately to the sustained activation of a population of fibroblasts that deposit increased amounts of extracellular matrix in lesional tissues, including the skin and internal organs.

Impairment of the immune system is currently thought to play an important role. This is based on the observation that in the early phases of SSc, mononuclear cells migrate to the dermis and accumulate around small blood vessels, nerves and skin appendages. Furthermore, there is a direct relation between the extent of cutaneous inflammation and the extent and progression of fibrosis of the skin. Stimulated T-lymphocytes of patients with SSc produce more tumor necrosis factor-α, interleukin-1 and -2 compared with healthy controls and the serum concentrations of IL-2, IL-4, IL-6 and IL-8 and soluble IL-2 receptors are elevated. The occurrence of autoantibodies, predominantly antitopoisomerase-1 (ATA) and anticentromere antibodies (ACA), in approximately 90% of the patients, points to an alteration of the humoral immune system.

Systemic sclerosis can be subdivided into diffuse and limited forms. Diffuse cutaneous SSc (dcSSc) is characterised by skin involvement proximal to the elbows and knees, limited cutaneous SSc (lcSSc) by skin involvement distal to these joints. In approximately 50% of patients with dcSSc, ATA can be detected, and in approximately 50% of patients with lcSSc ACAs are present. Other hallmark autoantibodies have also been identified in smaller proportions of SSc patients including anti-RNA polymerase I/III and anti-fibrillarin antibodies (5).

The course of SSc is variable. In some patients the disease remains confined to sclerodactyly and Raynaud's phenomenon. In other patients there is a relentless progression of internal organ fibrosis, ultimately leading to death. A recent study showed a cumulative 5-year survival rate of 63%. There are efforts to try to identify clinical and investigational predictors of outcome in SSc. One study has identified three clinical variables: raised ESR, proteinuria and impaired lung function indices which are associated with poor outcome. In addition, the various hallmark autoantibodies occurring in SSc are mutually exclusive and several studies in Europe and North America have demonstrated that individuals carrying each of these autoantibodies are associated with different frequencies of internal organ complications. This also allows patients who are at increased risk of pulmonary, cardiac or renal complications to be identified.

At present, no treatment has been definitely shown to be effective in SSc. Because of its presumed immunologic pathogenesis, modulation of the immune system has been the major goal in therapeutic interventions in SSc. Several studies have reported effectiveness of immune modulating drugs in the treatment of this disease, although these have mostly been in open, uncontrolled trials. These drugs include azathioprine, cyclosporin, methotrexate and cyclophosphamide. Amongst these, methotrexate and cyclophosphamide are currently the most widely used. New, more specific immunological treatment modalities have been harnessed in order to improve the treatment and prognosis of scleroderma patients.

In 2005, a patient with systemic sclerosis was treated with AIMSPRO on a compassionate basis with a sustained improvement in mobility and, in particular, there was an improvement in proximal muscle power and skin characteristics.

In this study, twenty patients will receive either AIMSPRO or placebo, 1.0ml subcutaneously, twice weekly for 26 weeks. Standard outcome measures and novel biomarkers will be used to investigate safety, efficacy and response to treatment. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

• NCT number: NCT00769028
• Study type: Interventional
• Source: Daval International Limited
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 2008
• Completion date: September 2011