Hepatitis C, Treatment Naïve, Genotype 1 Patients
Conditions
Brief summary
Phase 1, randomized, double-blind, placebo-controlled, dose-escalation study with 3 dose levels of IMO-2125 in combination with standard weight based ribavirin (investigational treatment arm) or placebo in combination with ribavirin (RBV). Each cohort of 15 patients will be randomized 4:1 to receive the investigational treatment arm (12 patients) or placebo and RBV arm (3 patients).
Detailed description
This is a phase 1, randomized, double-blind, placebo-controlled, dose-escalation study with 3 dose levels of IMO-2125 in combination with standard ribavirin or placebo plus ribavirin. Each cohort will be randomized 4:1 to receive the investigational treatment arm or placebo and ribavirin. Three varying dose levels of IMO-2125 will be included. In both arms, ribavirin will be dosed based on patient weight. Approximately 50 patients will be enrolled in France and Russia. Patients will provide informed consent prior to any screening procedures being performed. Screening will occur within 21 days prior to randomization. Enrolled patients who qualify and proceed successfully through the screening period will be randomized to receive 4 weeks of either the investigational treatment arm (IMO-2125 and ribavirin) or placebo and ribavirin, with a 4 week follow-up period. Patients who are randomized to the investigational treatment arm will receive one of 3 dose levels of IMO 2125 SC once weekly; each patient will receive the same dose throughout the 4 weeks of treatment. In addition to IMO-2125 treatment they will also receive daily ribavirin, which will be given based on the patients weight and will be taken twice daily for a total of 4 weeks.
Interventions
DRUGSaline
Subcutaneous injection once per week for four weeks
DRUGIMO-2125
IMO 2125 is a synthetic DNA-based agonist of Toll-like receptor 9, which is expressed in humans in plasmacytoid dendritic cells and B cells of the immune system.
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Documented genotype 1 * HCV-positive with documented detectable plasma viral concentration \> 10,000 IU/mL
Exclusion criteria
* Positive test for HIV or HbsAg * Inadequate bone marrow, liver, and renal function * Treatment with any IFN-based or other experimental or antiviral therapies - prior or current * Other significant medical disease * Concurrent or planned treatment during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| At Least 1 TEAE | From first dose of study treatment to day 59 (end of study) | The number and percentage of subjects who experienced at least one treatment-emergent adverse event by category. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Ribavirin Placebo cohort: Saline (placebo) sc once weekly + Ribavirin (1000 mg dose for patients \<75 kg; 1200 mg dose for patients ≥75 kg) administered orally in 2 divided oral doses. | 3 |
| IMO-2125 0.08 mg/kg Weekly + Ribavirin First experimental cohort: IMO-2125 0.08 mg/kg weekly + Ribavirin (1000 mg dose for patients \<75 kg; 1200 mg dose for patients ≥75 kg), administered orally in 2 divided oral doses. | 12 |
| IMO-2125 0.16 mg/kg Weekly + Ribavirin Second experimental cohort: IMO-2125 0.16 mg/kg weekly + Ribavirin (1000 mg dose for patients \<75 kg; 1200 mg dose for patients ≥75 kg), administered orally in 2 divided oral doses. | 12 |
| IMO-2125 0.32 mg/kg Weekly + Ribavirin Third experimental cohort: IMO-2125 0.32 mg/kg weekly + Ribavirin (1000 mg dose for patients \<75 kg; 1200 mg dose for patients ≥75 kg), administered orally in 2 divided oral doses. | 12 |
| IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin Fourth experimental cohort: IMO-2125 0.16 mg/kg twice weekly + Ribavirin (1000 mg dose for patients \<75 kg; 1200 mg dose for patients ≥75 kg), administered orally in 2 divided oral doses. | 12 |
| Peg-rIFN + Ribavirin Active comparator cohort: Peg-rIFN 180 µg sc once weekly + Ribavirin (1000 mg dose for patients \<75 kg; 1200 mg dose for patients ≥75 kg) administered orally in 2 divided oral doses. | 12 |
| Total | 63 |
Baseline characteristics
| Characteristic | IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin | Peg-rIFN + Ribavirin | Total | IMO-2125 0.08 mg/kg Weekly + Ribavirin | Placebo + Ribavirin | IMO-2125 0.32 mg/kg Weekly + Ribavirin | IMO-2125 0.16 mg/kg Weekly + Ribavirin |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.5 years | 32.0 years | 39.0 years | 40.5 years | 30.0 years | 48.5 years | 38.0 years |
| Body Mass Index (BMI) | 24.1 kg/m^2 | 24.9 kg/m^2 | 24.8 kg/m^2 | 24.3 kg/m^2 | 22.4 kg/m^2 | 27.3 kg/m^2 | 22.7 kg/m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 12 Participants | 62 Participants | 12 Participants | 3 Participants | 12 Participants | 11 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 24 Participants | 3 Participants | 2 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 39 Participants | 9 Participants | 1 Participants | 7 Participants | 8 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 3 | 12 / 12 | 12 / 12 | 12 / 12 | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 3 | 2 / 12 | 7 / 12 | 2 / 12 | 3 / 12 | 11 / 12 |
Outcome results
Primary
At Least 1 TEAE
The number and percentage of subjects who experienced at least one treatment-emergent adverse event by category.
Time frame: From first dose of study treatment to day 59 (end of study)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + Ribavirin | At Least 1 TEAE | At least 1 TEAE that led to discontinuation | 0 Participants |
| Placebo + Ribavirin | At Least 1 TEAE | At least 1 injection site reaction | 0 Participants |
| Placebo + Ribavirin | At Least 1 TEAE | At least 2 TEAE related to study drug | 2 Participants |
| Placebo + Ribavirin | At Least 1 TEAE | At least 1 TEAE | 2 Participants |
| Placebo + Ribavirin | At Least 1 TEAE | At least 1 severe/life threatening TEAE | 0 Participants |
| IMO-2125 0.08 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE | 12 Participants |
| IMO-2125 0.08 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 severe/life threatening TEAE | 2 Participants |
| IMO-2125 0.08 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE that led to discontinuation | 0 Participants |
| IMO-2125 0.08 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 2 TEAE related to study drug | 12 Participants |
| IMO-2125 0.08 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 injection site reaction | 12 Participants |
| IMO-2125 0.16 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 severe/life threatening TEAE | 7 Participants |
| IMO-2125 0.16 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE | 12 Participants |
| IMO-2125 0.16 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 2 TEAE related to study drug | 12 Participants |
| IMO-2125 0.16 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 injection site reaction | 12 Participants |
| IMO-2125 0.16 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE that led to discontinuation | 0 Participants |
| IMO-2125 0.32 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 severe/life threatening TEAE | 2 Participants |
| IMO-2125 0.32 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 injection site reaction | 11 Participants |
| IMO-2125 0.32 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 2 TEAE related to study drug | 12 Participants |
| IMO-2125 0.32 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE | 12 Participants |
| IMO-2125 0.32 mg/kg Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE that led to discontinuation | 0 Participants |
| IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin | At Least 1 TEAE | At least 2 TEAE related to study drug | 12 Participants |
| IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin | At Least 1 TEAE | At least 1 severe/life threatening TEAE | 3 Participants |
| IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE that led to discontinuation | 0 Participants |
| IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin | At Least 1 TEAE | At least 1 injection site reaction | 12 Participants |
| IMO-2125 0.16 mg/kg Twice Weekly + Ribavirin | At Least 1 TEAE | At least 1 TEAE | 12 Participants |
| Peg-rIFN + Ribavirin | At Least 1 TEAE | At least 1 injection site reaction | 9 Participants |
| Peg-rIFN + Ribavirin | At Least 1 TEAE | At least 1 TEAE that led to discontinuation | 0 Participants |
| Peg-rIFN + Ribavirin | At Least 1 TEAE | At least 1 TEAE | 12 Participants |
| Peg-rIFN + Ribavirin | At Least 1 TEAE | At least 2 TEAE related to study drug | 12 Participants |
| Peg-rIFN + Ribavirin | At Least 1 TEAE | At least 1 severe/life threatening TEAE | 7 Participants |