None listed
Conditions
Brief summary
A phase Ib, open label, dose escalation study of the safety, tolerability and immunogenicity of oglufanide disodium in patients with chronic hepatitis C who have declined or are nonresponsive to conventional antiviral therapy.
Interventions
Oglufanide disodium is to be administered for 5 of 7 days for two successive weeks, followed by two weeks without therapy. This 4 week cycle will be repeated 3 times. The first 7 cohorts will receive dose levels of 0.5ug, 5ug, 50ug, 500ug, 5mg, 15mg and 50mg subcutaneously with the 8th cohort receiving 5mg inhaled. Escalation to the next dose will only commence if no adverse event that is severe and/or serious and considered probably or definately related to the study product has been observed b
Oglufanide disodium is to be administered for 5 of 7 days for two successive weeks, followed by two weeks without therapy. This 4 week cycle will be repeated 3 times. The first 7 cohorts will receive dose levels of 0.5ug, 5ug, 50ug, 500ug, 5mg, 15mg and 50mg subcutaneously with the 8th cohort receiving 5mg inhaled. Escalation to the next dose will only commence if no adverse event that is severe and/or serious and considered probably or definately related to the study product has been observed by the time all subjects in the previous dose level group have completed their second two week cycle of therapy.
Sponsors
Implicit Bioscience Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Serological evidence of hepatitis C infection by anti-HCV antibody test and HCV RNA detectable by PCR; Liver biopsy showing Metavir fibrosis stage = or <2 within 3 or 5 years, for moderate or mild disease respectively; Able to give written informed consent and comply with protocol requirements; Has failed to respond to conventional antiviral therapy, has relapsed, or has declined to receive these drugs (previous ribavirin treatment must be >6 months prior to enrolment).
Exclusion criteria
Women who are pregnant, breastfeeding or of child-bearing potential who are not using at least two forms of acceptable methods of birth control; Co-infection with HBV or HIV; Patients who are expected to need systemic antiviral therapy at any time during their participation; Renal impairment (creatinine >0.15 mmol/L; Specific enzymes > 5x upper limit of normal, bilirubin> 30umol/L; Haematological abnormalities (Hb <110g/L, lymphocyte count <0.8x10^9/L, platelet count <100x10^9/L); History or evidence of bleeding from oesphageal varices or other conditions consistent with decompensated liver disease; History or evidence of chronic pulmonary disease associated with functional limitations; History of major organ transplantation with an existing functional graft; Haemophilia or any other condition that would preclude liver biopsy; Alcohol intake >30g/day for men or >20g/day for women or evidence of alcohol abuse within 6 months of screening; Poorly controlled diabetes mellitus; Patients taking herbal or antioxidant therapies; Substance abuse with IV or inhaled drugs; Evidence of liver disease due to other disorders (eg. untreated haemochromatosis, alcoholic liver disease, Wilson's disease, autoimmune hepatitis, toxin exposure, alpha1-antitrypsin); Persons currently (or within 3 months prior to enrolment) taking systemic immunosuppressive or immunomodulative medication including interferon (use of topical or inhalant corticosteroids is acceptable); Evidence of ongoing autoimmune disease (clinically manifest vasculitis, ANA titre >640, AMA titre >160, anti smooth muscle antibody titre >160); Acute illness within 72 hours prior to first drug administration; Administration of any investigational drug or vaccine or any registered vaccine within 30 days prior to and during the dosing phase in this study or within 5 half lives of the investigational drug, which ever is shorter; Any medical or social condition that in the opinion of the investigator would interfere with the interpretation or evaluation of the study product; Subjects in whom it is not possible to obtain a pre-dose blood sample without undue trauma or distress; Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is >20% within 2 years; Body mass index >36 or <18; Donation or loss of more than 400ml of blood within 2 months prior to anticipated dose administration; History of clinically significant drug allergy; History of a severe seizure disorder or current anticonvulsant use.
Outcome results
None listed