Trial Outcomes & Findings for Phase Ib/2, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Hepatocellular Carcinoma (NCT NCT02314052)
NCT ID: NCT02314052
Last Updated: 2024-07-11
Results Overview
Part A: 3 patient cohorts with 50% dose increase between cohorts until study drug-related dose-limiting toxicity (DLT) during Cycle 1, then expand to 6 patients and move to Part B. Part B: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation. Expand MTD cohort to 12 patients; tumor biopsies to be performed in this Phase 1b MTD Biopsy Cohort (6 patients).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose
Results posted on
2024-07-11
Participant Flow
Participant milestones
| Measure |
Cohort 1
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Cycle One
STARTED
|
3
|
3
|
3
|
3
|
6
|
3
|
|
Cycle One
COMPLETED
|
3
|
3
|
3
|
2
|
6
|
3
|
|
Cycle One
NOT COMPLETED
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Cycle Two
STARTED
|
3
|
3
|
3
|
2
|
6
|
3
|
|
Cycle Two
COMPLETED
|
3
|
2
|
2
|
1
|
2
|
3
|
|
Cycle Two
NOT COMPLETED
|
0
|
1
|
1
|
1
|
4
|
0
|
|
Cycle Three
STARTED
|
3
|
2
|
2
|
1
|
2
|
3
|
|
Cycle Three
COMPLETED
|
3
|
2
|
2
|
1
|
2
|
3
|
|
Cycle Three
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cycle Four
STARTED
|
3
|
2
|
2
|
1
|
2
|
3
|
|
Cycle Four
COMPLETED
|
0
|
2
|
1
|
0
|
2
|
0
|
|
Cycle Four
NOT COMPLETED
|
3
|
0
|
1
|
1
|
0
|
3
|
|
Cycle Five
STARTED
|
0
|
2
|
1
|
1
|
2
|
0
|
|
Cycle Five
COMPLETED
|
0
|
0
|
0
|
1
|
2
|
0
|
|
Cycle Five
NOT COMPLETED
|
0
|
2
|
1
|
0
|
0
|
0
|
|
Cycles 6 -10.5
STARTED
|
0
|
0
|
0
|
1
|
2
|
0
|
|
Cycles 6 -10.5
COMPLETED
|
0
|
0
|
0
|
1
|
2
|
0
|
|
Cycles 6 -10.5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Cycle One
Adverse Event
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Phase Ib/2, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Hepatocellular Carcinoma
Baseline characteristics by cohort
| Measure |
DCR-MYC
n=21 Participants
Patient groups (cohorts) will receive a single dose level of DCR-MYC; the dose level of DCR-MYC will be increased in subsequent cohorts
DCR-MYC: Dosing: 2 hour IV infusion on Day 1 and 8 of each 21 day cycle.
Starting dose: 0.125mg/kg/dose
Number of cycles: until progression or unacceptable toxicity develops.
PHASE 1b Dose escalation: 50% or 25% increase in subsequent cohorts depending upon toxicity until maximum tolerated dose (MTD) is identified.
PHASE 2 Cohort expansion at the MTD: Additional patients to be treated at the highest dose tolerated to assess efficacy and further assess safety
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
|
Age, Continuous
|
64.1 years
STANDARD_DEVIATION 7.24 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
South Korea
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dosePopulation: Safety population
Part A: 3 patient cohorts with 50% dose increase between cohorts until study drug-related dose-limiting toxicity (DLT) during Cycle 1, then expand to 6 patients and move to Part B. Part B: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation. Expand MTD cohort to 12 patients; tumor biopsies to be performed in this Phase 1b MTD Biopsy Cohort (6 patients).
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability
|
3 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
6 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dosePopulation: N/A - Study terminated prior to Phase 2
Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); further evaluation of safety and tolerability.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continuedPopulation: N/A - Study terminated prior to phase 2
Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); evaluation for evidence of objective response or disease stabilization.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Cmax: Day 1
|
2094.3 ng/mL
Standard Deviation 1257.8
|
4790.5 ng/mL
Standard Deviation 3540.2
|
6195.7 ng/mL
Standard Deviation 744.75
|
9807.1 ng/mL
Standard Deviation 4094.5
|
19399 ng/mL
Standard Deviation 8211.4
|
19829 ng/mL
Standard Deviation 3686.2
|
|
Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Cmax: Day 8
|
1755.7 ng/mL
Standard Deviation 59.47
|
5504.9 ng/mL
Standard Deviation 3365.3
|
6628.4 ng/mL
Standard Deviation 1155.8
|
13484 ng/mL
Standard Deviation 2576.2
|
20711 ng/mL
Standard Deviation 13768
|
27067 ng/mL
Standard Deviation 9105.1
|
SECONDARY outcome
Timeframe: Cycle 1; Week 1Population: Safety population
Collection of blood samples for cytokine measurements (Day 1, 2, and 4). No noteworthy increases were observed across dose groups or time for GM-CSF, IFNα, IFNɣ, or IL-1β. Changes that were observed for the other cytokines were not dose-dependent since they occurred sporadically and primarily in Cohorts 3 (0.3 mg/kg) and 4 (0.45 mg/kg). Pre-dose, 4 hours post-dose, and 24 hour post-dose results for TNF-α, IL-10, IL-6, IL-8, IL-1RA, and MCP-1 are summarized here.
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-6 4 hour post-dose
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
38.3 pg/mL
Standard Deviation 51.9
|
133.7 pg/mL
Standard Deviation 228.7
|
1.6 pg/mL
Standard Deviation 0
|
4.7 pg/mL
Standard Deviation 5.3
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-6 24 hour post-dose
|
2.2 pg/mL
Standard Deviation 1.0
|
1.6 pg/mL
Standard Deviation 0
|
6.3 pg/mL
Standard Deviation 6.6
|
1.6 pg/mL
Standard Deviation 0
|
3.8 pg/mL
Standard Deviation 3.8
|
19.2 pg/mL
Standard Deviation 26.8
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-8 4 hour post-dose
|
8.2 pg/mL
Standard Deviation 3.1
|
2.3 pg/mL
Standard Deviation 1.2
|
57.1 pg/mL
Standard Deviation 64.0
|
89.8 pg/mL
Standard Deviation 144.5
|
10.4 pg/mL
Standard Deviation 11.4
|
13.2 pg/mL
Standard Deviation 11.1
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-8 24 hour post-dose
|
9.0 pg/mL
Standard Deviation 2.8
|
5.9 pg/mL
Standard Deviation 3.9
|
16.7 pg/mL
Standard Deviation 8.2
|
9.8 pg/mL
Standard Deviation 1.5
|
25.8 pg/mL
Standard Deviation 37.2
|
26.1 pg/mL
Standard Deviation 11.2
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-IRA pre-dose
|
10.2 pg/mL
Standard Deviation 7.7
|
26.4 pg/mL
Standard Deviation 26.3
|
29.5 pg/mL
Standard Deviation 16.1
|
2.8 pg/mL
Standard Deviation 2.1
|
26.5 pg/mL
Standard Deviation 42.7
|
1.6 pg/mL
Standard Deviation 0
|
|
DCR-MYC Biological Activities (Phase 1b Only)
TNF-α 24 hour post-dose
|
1.6 pg/mL
Standard Deviation 0
|
4.1 pg/mL
Standard Deviation 0.5
|
4.5 pg/mL
Standard Deviation 1.2
|
3.3 pg/mL
Standard Deviation 2.9
|
2.4 pg/mL
Standard Deviation 1.7
|
3.8 pg/mL
Standard Deviation 3.8
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-10 24 hour post
|
322.5 pg/mL
Standard Deviation 152.9
|
424.4 pg/mL
Standard Deviation 296.4
|
939.3 pg/mL
Standard Deviation 939.3
|
667.7 pg/mL
Standard Deviation 362.7
|
541.8 pg/mL
Standard Deviation 240.9
|
830.7 pg/mL
Standard Deviation 333.3
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-6 pre-dose
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
7.9 pg/mL
Standard Deviation 10.9
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-10 4 hour post
|
241.1 pg/mL
Standard Deviation 61.3
|
159.6 pg/mL
Standard Deviation 104.2
|
933.1 pg/mL
Standard Deviation 427.2
|
1316.7 pg/mL
Standard Deviation 1617.7
|
527.1 pg/mL
Standard Deviation 225.5
|
533.7 pg/mL
Standard Deviation 265.6
|
|
DCR-MYC Biological Activities (Phase 1b Only)
TNF-α Pre-dose
|
2.3 pg/mL
Standard Deviation 1.3
|
1.6 pg/mL
Standard Deviation 0
|
4.1 pg/mL
Standard Deviation 0.7
|
1.6 pg/mL
Standard Deviation 0
|
3.1 pg/mL
Standard Deviation 3.0
|
1.6 pg/mL
Standard Deviation 0
|
|
DCR-MYC Biological Activities (Phase 1b Only)
TNF-α 4 hour post-dose
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
15.9 pg/mL
Standard Deviation 16.6
|
23.1 pg/mL
Standard Deviation 34.2
|
1.6 pg/mL
Standard Deviation 0
|
1.6 pg/mL
Standard Deviation 0
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-10 pre-dose
|
317.5 pg/mL
Standard Deviation 60.9
|
239.4 pg/mL
Standard Deviation 83.7
|
741.1 pg/mL
Standard Deviation 46.7
|
574.3 pg/mL
Standard Deviation 341.0
|
670.2 pg/mL
Standard Deviation 369.4
|
599.7 pg/mL
Standard Deviation 333.8
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-IRA 4 hour post-dose
|
4.1 pg/mL
Standard Deviation 4.3
|
3.3 pg/mL
Standard Deviation 2.9
|
1268.5 pg/mL
Standard Deviation 1733.8
|
3055.1 pg/mL
Standard Deviation 5286.2
|
5.4 pg/mL
Standard Deviation 8.6
|
1.6 pg/mL
Standard Deviation 0
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-IRA 24 hour post-dose
|
5.3 pg/mL
Standard Deviation 6.4
|
13.3 pg/mL
Standard Deviation 10.2
|
40.5 pg/mL
Standard Deviation 8.6
|
4.5 pg/mL
Standard Deviation 5.1
|
9.0 pg/mL
Standard Deviation 16.6
|
1.6 pg/mL
Standard Deviation 0
|
|
DCR-MYC Biological Activities (Phase 1b Only)
IL-8 pre-dose
|
8.7 pg/mL
Standard Deviation 2.7
|
2.2 pg/mL
Standard Deviation 1.0
|
8.1 pg/mL
Standard Deviation 4.7
|
4.0 pg/mL
Standard Deviation 2.2
|
11.9 pg/mL
Standard Deviation 16.3
|
18.6 pg/mL
Standard Deviation 14.7
|
|
DCR-MYC Biological Activities (Phase 1b Only)
MCP-1 pre-dose
|
101.2 pg/mL
Standard Deviation 13.1
|
76.5 pg/mL
Standard Deviation 59.8
|
70.5 pg/mL
Standard Deviation 17.5
|
111.7 pg/mL
Standard Deviation 3.52
|
244.5 pg/mL
Standard Deviation 210.5
|
164.4 pg/mL
Standard Deviation 134.1
|
|
DCR-MYC Biological Activities (Phase 1b Only)
MCP-1 4 hour post-dose
|
90.0 pg/mL
Standard Deviation 18.8
|
46.0 pg/mL
Standard Deviation 23.6
|
718.8 pg/mL
Standard Deviation 872.8
|
1202.5 pg/mL
Standard Deviation 1811.4
|
160.2 pg/mL
Standard Deviation 117.7
|
137.2 pg/mL
Standard Deviation 33.1
|
|
DCR-MYC Biological Activities (Phase 1b Only)
MCP-1 24 hour post-dose
|
162.1 pg/mL
Standard Deviation 69.8
|
119.5 pg/mL
Standard Deviation 69.0
|
206.9 pg/mL
Standard Deviation 118.6
|
184.6 pg/mL
Standard Deviation 22.7
|
316.6 pg/mL
Standard Deviation 198.4
|
445.8 pg/mL
Standard Deviation 337.8
|
SECONDARY outcome
Timeframe: Cycle 1 and 2Population: Planned expansion into the MTD biopsy cohort and phase 2 portion of the study did not occur due to the sponsor's decision to prematurely end the study.
Tumor biopsies (2 total) to be performed in Phase 1b MTD expansion cohort only (6 patients). Patients will have biopsies performed prior to Cycle 1/Day 1 and on Cycle 2/Day 11.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Tmax: Day 8
|
2.6 hr
Standard Deviation 0.60
|
2.4 hr
Standard Deviation 0.13
|
2.7 hr
Standard Deviation 0.35
|
2.2 hr
Standard Deviation 0.24
|
3.0 hr
Standard Deviation 0.72
|
2.2 hr
Standard Deviation 0.24
|
|
Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Tmax: Day 1
|
2.4 hr
Standard Deviation 0.14
|
2.7 hr
Standard Deviation 0.68
|
2.6 hr
Standard Deviation 0.27
|
2.9 hr
Standard Deviation 0.55
|
2.3 hr
Standard Deviation 0.26
|
2.2 hr
Standard Deviation 0.14
|
SECONDARY outcome
Timeframe: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=33 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Cmax_D: Day 8
|
14045 kg*ng/mL/mg
Standard Deviation 475.74
|
27525 kg*ng/mL/mg
Standard Deviation 16827
|
22095 kg*ng/mL/mg
Standard Deviation 3852.7
|
29964 kg*ng/mL/mg
Standard Deviation 5724.8
|
30457 kg*ng/mL/mg
Standard Deviation 20247
|
31931 kg*ng/mL/mg
Standard Deviation 10677
|
|
Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Cmax_D: Day 1
|
16832 kg*ng/mL/mg
Standard Deviation 10192
|
23952 kg*ng/mL/mg
Standard Deviation 17701
|
20652 kg*ng/mL/mg
Standard Deviation 2482.5
|
21794 kg*ng/mL/mg
Standard Deviation 9098.8
|
28527 kg*ng/mL/mg
Standard Deviation 12076
|
23384 kg*ng/mL/mg
Standard Deviation 4241.4
|
SECONDARY outcome
Timeframe: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
AUClast_D: Day 1
|
178997 hr*kg*ng/mL/mg
Standard Deviation 125460
|
299295 hr*kg*ng/mL/mg
Standard Deviation 312426
|
197244 hr*kg*ng/mL/mg
Standard Deviation 116908
|
195133 hr*kg*ng/mL/mg
Standard Deviation 56544
|
290201 hr*kg*ng/mL/mg
Standard Deviation 169069
|
201529 hr*kg*ng/mL/mg
Standard Deviation 45290
|
|
AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
AUClast_D: Day 8
|
163478 hr*kg*ng/mL/mg
Standard Deviation 109924
|
739203 hr*kg*ng/mL/mg
Standard Deviation 698459
|
389653 hr*kg*ng/mL/mg
Standard Deviation 293467
|
350625 hr*kg*ng/mL/mg
Standard Deviation 132910
|
274941 hr*kg*ng/mL/mg
Standard Deviation 168548
|
383537 hr*kg*ng/mL/mg
Standard Deviation 84286
|
SECONDARY outcome
Timeframe: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Outcome measures
| Measure |
Cohort 1
n=3 Participants
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 Participants
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 Participants
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 Participants
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 Participants
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 Participants
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
AUClast : Day 1
|
22375 hr*ng/mL
Standard Deviation 15683
|
59859 hr*ng/mL
Standard Deviation 62485
|
59173 hr*ng/mL
Standard Deviation 35072
|
87810 hr*ng/mL
Standard Deviation 25445
|
197337 hr*ng/mL
Standard Deviation 114967
|
171299 hr*ng/mL
Standard Deviation 38496
|
|
AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
AUClast : Day 8
|
20435 hr*ng/mL
Standard Deviation 13741
|
147841 hr*ng/mL
Standard Deviation 139692
|
116896 hr*ng/mL
Standard Deviation 88040
|
157781 hr*ng/mL
Standard Deviation 59810
|
186960 hr*ng/mL
Standard Deviation 114612
|
326006 hr*ng/mL
Standard Deviation 71643
|
Adverse Events
Cohort 1
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Cohort 2
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 3 deaths
Cohort 4
Serious events: 1 serious events
Other events: 3 other events
Deaths: 1 deaths
Cohort 5
Serious events: 2 serious events
Other events: 6 other events
Deaths: 3 deaths
Cohort 6
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Cohort 1
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 participants at risk
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Spinal cord compression/ Spinal Cord Compression Due To Pathologic Fracture Of T1
|
33.3%
1/3 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain/ Sore Throat
|
33.3%
1/3 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea/ Increased Dyspnea
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
General disorders
Influenza like illness/ Flu Like Symptom
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Cardiac disorders
Acute coronary syndrome/ Acute Coronary Syndrome
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Hepatobiliary disorders
Cholangitis/ Cholangitis Due To Pd
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone/ Osteolytic Jaw Lesion Due To Progression Disease
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Vascular disorders
Hypovolaemic shock/ Hypovolemic Hypoperfusion
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Number of events 1 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
Other adverse events
| Measure |
Cohort 1
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 2
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 3
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 4
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 5
n=6 participants at risk
N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
Cohort 6
n=3 participants at risk
N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
|
|---|---|---|---|---|---|---|
|
General disorders
Fatigue
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
General disorders
Oedema peripheral
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
2/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
General disorders
Pyrexia
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
General disorders
Chills
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
General disorders
Influenza-like illness
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
General disorders
Pain
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Gastrointestinal disorders
Ascites
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Gastrointestinal disorders
Abdominal distention
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
2/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
2/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
AST increased
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
ALT increased
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
Lipase increased
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
Blood bilirubin increased
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
GGT increased
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
2/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
16.7%
1/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
66.7%
2/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
0.00%
0/6 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
33.3%
1/3 • Throughout entire duration of the study (e.g., approximately 3 month period)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee SPONSOR agrees that the Principal Investigator shall have the right to publish or permit the publication of any information or material relating to or arising out of the work after prior submittal to SPONSOR provided that if SPONSOR shall so request, the investigator will delay publication for a maximum of ninety (90) days after submittal to SPONSOR to enable SPONSOR to protect its rights. SPONSOR will comment on such documents within thirty (30) days.
- Publication restrictions are in place
Restriction type: OTHER