Clinical trial NCT00983060: Adaptive-design Dose Finding Study to Assess the Antiviral Efficacy and Safety of NIM811 Administered in Combination With Standard of Care (SOC) in Relapsed Hepatitis C Virus 1 (HCV-1) Infected Patients
Official title: A Randomized, Adaptive-design, Dose-finding Study to Assess the Antiviral Efficacy and Safety of NIM811 Administered in Combination With the Standard of Care (SOC) in Relapsed Patients Infected With HCV Genotype-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C Genotype-1 Relapse
Keywords: NIM811
chronic hepatitis
chronic hepatitis C
chronic hepatitis C genotype-1
HCV
HCV-1
relapser
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-09-23
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study designed to identify a dose of NIM811 that has a good safety profile, is well tolerated when co-administered with SOC, and provides a clinically meaningful effect in viral load reduction compared to SOC alone. This information will be used to support doses selected for future studies.


Eligibility criteria: Inclusion criteria:

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

* chronic hepatitis C genotype-1
* HCV-RNA should be ≥ 4 x 105 IU/mL at screening
* Recipient of prior long acting interferon and ribavirin treatment for at least 12 weeks, with documented negative serum HCV RNA on treatment, who subsequently becomes serum HCV RNA positive after stopping treatment ("relapser"). Patients must have been off all treatment for at least 3 months prior to start of study (Visit

Exclusion criteria:

* Use of any HCV treatment ≤ 3months prior to study start
* Prior receipt of any investigational anti-HCV therapy which is not IFN or RBV
* Women of child-bearing potential unless they are post-menopausal or use predefined acceptable methods of contraception
* Pregnant or breastfeeding women
* Evidence of cirrhosis, hepatic decompensation, other than HCV liver disease, HBV or HIV infection
* Specified abnormalities in lab values of amongst others hemoglobin, WBC, ANC, platelets
* History of treatment for depression
* Steroid/immunosuppression drug use 3 months prior to study start Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: To evaluate the safety and tolerability of NIM811 dosed daily for 4 weeks in combination with SOC
timeFrame: 4 weeks
Secondary outcomes:
measure: To identify a dose of NIM811 which is safe and tolerated and produces in combination with SOC a clinically meaningful improvement over SOC monotherapy in antiviral response Time Frame: 4 weeks
timeFrame: 12 weeks
measure: To assess the percentage of patients achieving rapid virologic response (RVR) in patients treated with NIM811 in combination with SOC
timeFrame: 4 weeks
measure: To explore the pharmacokinetics and pharmacodynamics of NIM811 given in combination with SOC in patients with chronic hepatitis C genotype-1
timeFrame: 3 weeks, 5 weeks
measure: To evaluate the effect of NIM811 given in combination with SOC in patients with chronic hepatitis C genotype-1 on sustained virologic response 12 weeks after cessation of treatment (SVR12)
timeFrame: 12 weeks after cessation of treatment
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Research and Education Inc.
state: California
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Sarasota
country: United States
facility: University Hepatitis Center
state: Florida
city: Tampa
country: United States
facility: West Wind'r Research & Development LLC
state: Florida
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Wentworthville
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Brussels
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: ROC
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Lawitz E, Godofsky E, Rouzier R, Marbury T, Nguyen T, Ke J, Huang M, Praestgaard J, Serra D, Evans TG. Safety, pharmacokinetics, and antiviral activity of the cyclophilin inhibitor NIM811 alone or in combination with pegylated interferon in HCV-infected patients receiving 14 days of therapy. Antiviral Res. 2011 Mar;89(3):238-45. doi: 10.1016/j.antiviral.2011.01.003. Epub 2011 Jan 19.