Hepatitis C
Conditions
Keywords
Hepatitis C, unresponsive to pegylated interferon and ribavirin therapy, hepatitis C virus
Brief summary
First-in-humans, phase 1, dose-escalation study with 4 dose levels of single-agent IMO-2125.
Detailed description
First-in-humans, phase 1, dose-escalation study with 4 dose levels of single-agent IMO-2125. Patients will proceed through a screening period, treatment period, and follow-up period of approximately 4 months' duration. There will be 4 dose cohorts including active drug and placebo dosing.
Interventions
DRUGIMO-2125
IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system
DRUGSaline placebo
saline placebo given subcutaneously
Sponsors
Idera Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HCV-positive * Nonresponder to standard-dose pegylated interferon-α-2a or -α-2b in combination with standard-dose ribavirin
Exclusion criteria
* Human immunodeficiency virus (HIV)or hepatitis B surface antigen (HbsAg) * Inadequate bone marrow, liver, and renal function * Treatment with any IFN (interferon)-based or other experimental or antiviral therapies within 30 days * Other significant medical diseases * Known alcohol or drug abuse within the past 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Safety. | From screening through study completion, 86 to 115 days in total | Count and percentage of subjects with treatment emergent adverse events |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study enrolled patients with chronic infection with hepatitis C virus (HCV) who were null responders to prior treatment with pegylated-interferon-alfa (peg-IFN-α) plus ribavirin. The study included patients with any HCV genotype.
Pre-assignment details
All enrolled subjects who qualified after the pre-screening period were assigned to a treatment group and treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Weekly saline placebo
Saline placebo: saline placebo given subcutaneously | 10 |
| IMO-2125 0.04 mg/kg q Week IMO-2125 given weekly at 0.04 mg/kg
IMO-2125: IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system | 8 |
| IMO-2125 0.08 mg/kg q Week IMO-2125 given weekly at 0.08 mg/kg
IMO-2125: IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system | 9 |
| IMO-2125 0.16 mg/kg q Week IMO-2125 given weekly at 0.16 mg/kg
IMO-2125: IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system | 8 |
| IMO-2125 0.32 mg/kg q Week IMO-2125 given weekly at 0.32 mg/kg
IMO-2125: IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system | 8 |
| IMO-2125 0.48 mg/kg q Week IMO-2125 given weekly at 0.48 mg/kg
IMO-2125: IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system | 8 |
| IMO-2125 0.16 mg/kg Twice a Week IMO-2125 given twice a week at 0.16 mg/kg
IMO-2125: IMO-2125 is a synthetic DNA-based agonist of Toll-like receptor 9 (TLR9), TLR9 is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system | 7 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | IMO-2125 0.16 mg/kg Twice a Week | IMO-2125 0.48 mg/kg q Week | IMO-2125 0.32 mg/kg q Week | IMO-2125 0.16 mg/kg q Week | Placebo | IMO-2125 0.08 mg/kg q Week | IMO-2125 0.04 mg/kg q Week |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54 years | 56 years | 52.5 years | 49 years | 55.5 years | 50 years | 51 years | 55 years |
| HCV Genotype 1a | 38 Participants | 4 Participants | 7 Participants | 4 Participants | 6 Participants | 7 Participants | 6 Participants | 4 Participants |
| HCV Genotype 1b | 19 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants |
| HCV Genotype 4a or 4c or 4d | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 8 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Female | 15 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 43 Participants | 6 Participants | 8 Participants | 7 Participants | 7 Participants | 4 Participants | 7 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 9 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 6 / 10 | 8 / 8 | 9 / 9 | 8 / 8 | 8 / 8 | 8 / 8 | 7 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 9 | 0 / 8 | 0 / 8 | 1 / 8 | 0 / 7 |
Outcome results
Primary
Evaluation of Safety.
Count and percentage of subjects with treatment emergent adverse events
Time frame: From screening through study completion, 86 to 115 days in total
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Evaluation of Safety. | Study drug-related TEAE | 5 Participants |
| Placebo | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| Placebo | Evaluation of Safety. | At least 1 TEAE | 6 Participants |
| Placebo | Evaluation of Safety. | TEAE leading to study drug discontinuation | 0 Participants |
| Placebo | Evaluation of Safety. | Serious Adverse Events | 0 Participants |
| IMO-2125 0.04 mg/kg q Week | Evaluation of Safety. | At least 1 TEAE | 8 Participants |
| IMO-2125 0.04 mg/kg q Week | Evaluation of Safety. | Study drug-related TEAE | 7 Participants |
| IMO-2125 0.04 mg/kg q Week | Evaluation of Safety. | Serious Adverse Events | 0 Participants |
| IMO-2125 0.04 mg/kg q Week | Evaluation of Safety. | TEAE leading to study drug discontinuation | 0 Participants |
| IMO-2125 0.04 mg/kg q Week | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| IMO-2125 0.08 mg/kg q Week | Evaluation of Safety. | TEAE leading to study drug discontinuation | 0 Participants |
| IMO-2125 0.08 mg/kg q Week | Evaluation of Safety. | At least 1 TEAE | 9 Participants |
| IMO-2125 0.08 mg/kg q Week | Evaluation of Safety. | Serious Adverse Events | 0 Participants |
| IMO-2125 0.08 mg/kg q Week | Evaluation of Safety. | Study drug-related TEAE | 9 Participants |
| IMO-2125 0.08 mg/kg q Week | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| IMO-2125 0.16 mg/kg q Week | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| IMO-2125 0.16 mg/kg q Week | Evaluation of Safety. | TEAE leading to study drug discontinuation | 0 Participants |
| IMO-2125 0.16 mg/kg q Week | Evaluation of Safety. | At least 1 TEAE | 8 Participants |
| IMO-2125 0.16 mg/kg q Week | Evaluation of Safety. | Serious Adverse Events | 0 Participants |
| IMO-2125 0.16 mg/kg q Week | Evaluation of Safety. | Study drug-related TEAE | 8 Participants |
| IMO-2125 0.32 mg/kg q Week | Evaluation of Safety. | Serious Adverse Events | 0 Participants |
| IMO-2125 0.32 mg/kg q Week | Evaluation of Safety. | At least 1 TEAE | 8 Participants |
| IMO-2125 0.32 mg/kg q Week | Evaluation of Safety. | Study drug-related TEAE | 8 Participants |
| IMO-2125 0.32 mg/kg q Week | Evaluation of Safety. | TEAE leading to study drug discontinuation | 0 Participants |
| IMO-2125 0.32 mg/kg q Week | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| IMO-2125 0.48 mg/kg q Week | Evaluation of Safety. | TEAE leading to study drug discontinuation | 1 Participants |
| IMO-2125 0.48 mg/kg q Week | Evaluation of Safety. | Study drug-related TEAE | 8 Participants |
| IMO-2125 0.48 mg/kg q Week | Evaluation of Safety. | Serious Adverse Events | 1 Participants |
| IMO-2125 0.48 mg/kg q Week | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| IMO-2125 0.48 mg/kg q Week | Evaluation of Safety. | At least 1 TEAE | 8 Participants |
| IMO-2125 0.16 mg/kg Twice a Week | Evaluation of Safety. | Serious Adverse Events | 0 Participants |
| IMO-2125 0.16 mg/kg Twice a Week | Evaluation of Safety. | Study drug-related TEAE | 7 Participants |
| IMO-2125 0.16 mg/kg Twice a Week | Evaluation of Safety. | Related TEAE causing study drug discontinuation | 0 Participants |
| IMO-2125 0.16 mg/kg Twice a Week | Evaluation of Safety. | At least 1 TEAE | 7 Participants |
| IMO-2125 0.16 mg/kg Twice a Week | Evaluation of Safety. | TEAE leading to study drug discontinuation | 0 Participants |