Trial Outcomes & Findings for Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer (NCT NCT04034355)
NCT ID: NCT04034355
Last Updated: 2022-01-26
Results Overview
Percentage of patients (with moderate or severe chronic CIPN) scoring 3 or 4 in at least 1 of the first 4 items of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13-item subscale (FACT/GOG-NTX-13; i.e., FACT/GOG-NTX-4) 9 months after the first dose of IMP (i.e. PledOx or placebo administered on Day 1, Cycle 1 of mFOLFOX6 chemotherapy). The FACT/GOG-13 questionnaire includes 13 items that measure the severity and impact of symptoms of neurotoxicity over the past 7 days. Patients rate each item as 0 ("not at all"), 1 (" a little bit"), 2 ("somewhat"), 3 ("quite a bit") or 4 ("very much"). These 13 items are summed to create a total score, ranging from 0 to 52, with a higher score representing a worse outcome. The FACT/GOG-NTX-4 is a 4 item subscale targeting numbness, tingling or discomfort in hands and/or feet.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
301 participants
Primary outcome timeframe
9 months
Results posted on
2022-01-26
Participant Flow
Patients were recruited in the EU and Asia between 7 January 2019 and 1 March 2020. The Sponsor placed recruitment/dosing in the POLAR program on hold following interactions with the French regulatory authority and the US clinical hold of study POLAR-M on 23 January 2020. As of 2 March 2020, no more patients were enrolled or IMP administered. Enrolled patients were followed until the data cut-off date of 31 August 2020 and these patients have been assigned as "completed" in the disposition.
371 patients were screened in the 28 days before the start of treatment, 301 were randomised and 297 were treated.
Participant milestones
| Measure |
PledOx (5 µmol/kg)
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Overall Study
STARTED
|
151
|
150
|
|
Overall Study
Treated
|
147
|
150
|
|
Overall Study
COMPLETED
|
117
|
115
|
|
Overall Study
NOT COMPLETED
|
34
|
35
|
Reasons for withdrawal
| Measure |
PledOx (5 µmol/kg)
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Overall Study
Study terminated by Sponsor
|
10
|
17
|
|
Overall Study
Withdrawal by Subject
|
12
|
11
|
|
Overall Study
Site terminated by Sponsor
|
4
|
5
|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Not reported
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Progressive disease
|
1
|
0
|
Baseline Characteristics
Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer
Baseline characteristics by cohort
| Measure |
PledOx (5 µmol/kg)
n=147 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=150 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
Total
n=297 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.3 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
62.4 years
STANDARD_DEVIATION 10.2 • n=7 Participants
|
62.9 years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
69 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
78 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
167 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
43 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
87 Participants
n=5 Participants
|
93 Participants
n=7 Participants
|
180 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Body Mass Index
|
24.20 kg/m^2
n=5 Participants
|
23.60 kg/m^2
n=7 Participants
|
24.20 kg/m^2
n=5 Participants
|
|
ECOG performance status
0
|
118 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
240 Participants
n=5 Participants
|
|
ECOG performance status
1
|
29 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 9 monthsPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Percentage of patients (with moderate or severe chronic CIPN) scoring 3 or 4 in at least 1 of the first 4 items of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13-item subscale (FACT/GOG-NTX-13; i.e., FACT/GOG-NTX-4) 9 months after the first dose of IMP (i.e. PledOx or placebo administered on Day 1, Cycle 1 of mFOLFOX6 chemotherapy). The FACT/GOG-13 questionnaire includes 13 items that measure the severity and impact of symptoms of neurotoxicity over the past 7 days. Patients rate each item as 0 ("not at all"), 1 (" a little bit"), 2 ("somewhat"), 3 ("quite a bit") or 4 ("very much"). These 13 items are summed to create a total score, ranging from 0 to 52, with a higher score representing a worse outcome. The FACT/GOG-NTX-4 is a 4 item subscale targeting numbness, tingling or discomfort in hands and/or feet.
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=120 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=119 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Moderate or Severe Chronic Chemotherapy Induced Peripheral Neuropathy (CIPN)
|
68 Participants
|
46 Participants
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Percentage of patients (with mild, moderate or severe chronic CIPN) scoring 2, 3 or 4 in at least 1 of the first 4 items of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13-item subscale (FACT/GOG-NTX-13; i.e., FACT/GOG-NTX-4) 9 months after the first dose of IMP (i.e. PledOx or placebo administered on Day 1, Cycle 1 of mFOLFOX6 chemotherapy). The FACT/GOG-13 questionnaire includes 13 items that measure the severity and impact of symptoms of neurotoxicity over the past 7 days. Patients rate each item as 0 ("not at all"), 1 (" a little bit"), 2 ("somewhat"), 3 ("quite a bit") or 4 ("very much"). These 13 items are summed to create a total score, ranging from 0 to 52, with a higher score representing a worse outcome. The FACT/GOG-NTX-4 is a 4 item subscale targeting numbness, tingling or discomfort in hands and/or feet.
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=120 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=119 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Mild, Moderate or Severe Chronic Chemotherapy Induced Peripheral Neuropathy
|
89 Participants
|
74 Participants
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Mean change from baseline in sensitivity to touching cold items on Day 2, Cycle 4 (cycle is 14 days) of mFOLFOX6 chemotherapy, as assessed by the Cold Sensitivity questionnaire. Cold sensitivity was rated 0 (not at all) to 10 (as bad as you can imagine).
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=120 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=126 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Sensitivity to Touching Cold Items
|
4.38 Scores on a scale
Interval 3.85 to 4.92
|
4.08 Scores on a scale
Interval 3.55 to 4.61
|
SECONDARY outcome
Timeframe: 9 monthsPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Mean cumulative dose of oxaliplatin administered per patient during mFOLFOX6 chemotherapy, 9 months after the first dose of Investigational Medicinal Product
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=138 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=140 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Cumulative Dose of Oxaliplatin During Chemotherapy
|
747.3 mg/m^2
Interval 705.5 to 789.2
|
755.0 mg/m^2
Interval 713.3 to 796.6
|
SECONDARY outcome
Timeframe: Baseline and 9 monthsPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Mean change from baseline in vibration sense, on the lateral malleolus (left and right), using a graduated tuning fork, at 9 months after the first dose of Investigational Medicinal Product. When the tuning fork was struck against the ball of the thumb, the base of the tuning fork was placed over the appropriate bony surface (i.e. lateral malleolus left and right) and the patient was asked to indicate the moment when the vibration was no longer detected. The intensity at which the patient no longer detected the vibration is reported on a scale of 0 (minimum score, representing the maximum vibration amplitude) to 8 (maximum score, representing the minimum vibration amplitude)
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=108 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=107 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Vibration Sensitivity on the Lateral Malleolus
|
-1.38 Scores on a scale
Standard Deviation 1.61
|
-1.43 Scores on a scale
Standard Deviation 1.84
|
SECONDARY outcome
Timeframe: Baseline and 9 monthsPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Mean change from baseline in worst pain in hands or feet in the past week, using a numerical rating scale (Numeric Rating Scale; Scale range of 0-10;0 = no pain, 10= pain as bad as you can imagine), at 9 months after the first dose of Investigational Medicinal Product
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=114 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=118 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Worst Pain in Hands or Feet
|
2.55 Scores on a scale
Interval 1.97 to 3.14
|
2.16 Scores on a scale
Interval 1.58 to 2.74
|
SECONDARY outcome
Timeframe: Baseline and 9 monthsPopulation: Modified ITT (mITT) analysis set including patients that fulfilled at least one of the following criteria: * the patient was randomized prior to 1 Dec 2019 (i.e. the patient was eligible for at least 3 months of IMP) and had at least one post-baseline assessment for efficacy, or * the 3 month Assessment Visit occurred prior to 1 Mar 2020, or * the patient received the 6th cycle of IMP after 1 Mar 2020.
Mean change from baseline in the time to complete the grooved Pegboard with the non-dominant hand, at 9 months after the first dose of Investigational Medicinal Product
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=104 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=107 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Functional Impairment (in the Non-dominant Hand)
|
16.23 seconds
Standard Deviation 48.91
|
-0.39 seconds
Standard Deviation 42.58
|
SECONDARY outcome
Timeframe: Analysis was planned at 24 months but performed based on available data at cut-off 31 August 2020 as the study was terminated early by the SponsorPopulation: Safety analysis set consisting of all randomized patients who received at least one dose of IMP. Patients were analyzed according to the study treatment they actually received.
Patients with disease free survival.
Outcome measures
| Measure |
PledOx (5 µmol/kg)
n=147 Participants
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=150 Participants
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Patients With Disease Free Survival
|
7 participants
|
15 participants
|
Adverse Events
PledOx (5 µmol/kg)
Serious events: 20 serious events
Other events: 146 other events
Deaths: 1 deaths
Placebo
Serious events: 20 serious events
Other events: 146 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
PledOx (5 µmol/kg)
n=147 participants at risk
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=150 participants at risk
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Colitis
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Crohn's disease
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Ileus
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
General disorders
Administration site cellulitis
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Immune system disorders
Anaphylactic reaction
|
1.4%
2/147 • Number of events 2 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Immune system disorders
Drug hypersensitivity
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Immune system disorders
Infusion related reaction
|
2.0%
3/147 • Number of events 5 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Clostridium difficile infection
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Corona virus infection
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Device related infection
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Infection
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Influenza
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Pneumonia
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Urinary tract infection
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Injury, poisoning and procedural complications
Gastrointestinal stoma complications
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Metabolism and nutrition disorders
Decreased appetitie
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Metabolism and nutrition disorders
Diabetic metabolic decompensation
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Cerebral infarction
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Product Issues
Device extrusion
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Renal and urinary disorders
Acute kidney injury
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Renal and urinary disorders
Renal failure
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal inflammation
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.4%
2/147 • Number of events 2 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/147 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.67%
1/150 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Vascular disorders
Embolism
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Vascular disorders
Vena cava thrombosis
|
0.68%
1/147 • Number of events 1 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
0.00%
0/150 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
Other adverse events
| Measure |
PledOx (5 µmol/kg)
n=147 participants at risk
Calmangafodipir 5 µmol/kg
Calmangafodipir (5 µmol/kg): PledOx will be given to patients as an i.v. infusion, on top of mFOLFOX6 chemotherapy. PledOx is a solution in 20 mL single dose glass vials.
|
Placebo
n=150 participants at risk
0.9% sodium chloride in 20 mL vials
Placebo: Placebo will be administered via the same route as PledOx (i.v. infusion). Placebo is a solution in 20 mL single dose glass vials.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.6%
17/147 • Number of events 24 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
11.3%
17/150 • Number of events 20 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.2%
18/147 • Number of events 34 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
12.7%
19/150 • Number of events 40 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Blood and lymphatic system disorders
Neutropenia
|
42.2%
62/147 • Number of events 144 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
45.3%
68/150 • Number of events 203 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
31.3%
46/147 • Number of events 69 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
38.7%
58/150 • Number of events 134 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
8.8%
13/147 • Number of events 18 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
9.3%
14/150 • Number of events 18 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.4%
8/147 • Number of events 9 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
10.0%
15/150 • Number of events 21 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Constipation
|
20.4%
30/147 • Number of events 38 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
16.7%
25/150 • Number of events 39 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
40.1%
59/147 • Number of events 120 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
37.3%
56/150 • Number of events 90 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Dry mouth
|
2.7%
4/147 • Number of events 4 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
6.0%
9/150 • Number of events 9 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
6.8%
10/147 • Number of events 10 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
7.3%
11/150 • Number of events 13 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Nausea
|
59.9%
88/147 • Number of events 193 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
46.0%
69/150 • Number of events 155 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Stomatitis
|
34.0%
50/147 • Number of events 67 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
20.7%
31/150 • Number of events 37 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Gastrointestinal disorders
Vomiting
|
18.4%
27/147 • Number of events 33 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
18.0%
27/150 • Number of events 34 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
General disorders
Asthenia
|
21.8%
32/147 • Number of events 87 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
24.0%
36/150 • Number of events 73 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
General disorders
Fatigue
|
26.5%
39/147 • Number of events 61 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
24.0%
36/150 • Number of events 78 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
General disorders
Malaise
|
5.4%
8/147 • Number of events 23 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
4.7%
7/150 • Number of events 9 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
General disorders
Pyrexia
|
6.8%
10/147 • Number of events 13 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
8.7%
13/150 • Number of events 18 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Immune system disorders
Infusion related reaction
|
5.4%
8/147 • Number of events 9 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
1.3%
2/150 • Number of events 2 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
8/147 • Number of events 8 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
4.7%
7/150 • Number of events 7 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Investigations
Alanine aminotransferase increased
|
7.5%
11/147 • Number of events 18 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
11.3%
17/150 • Number of events 26 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Investigations
Aspartate aminotransferase increased
|
7.5%
11/147 • Number of events 19 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
10.0%
15/150 • Number of events 23 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
28.6%
42/147 • Number of events 66 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
24.7%
37/150 • Number of events 62 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
3/147 • Number of events 5 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
7.3%
11/150 • Number of events 19 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.1%
9/147 • Number of events 11 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
1.3%
2/150 • Number of events 3 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.1%
9/147 • Number of events 12 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
4.0%
6/150 • Number of events 6 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.4%
8/147 • Number of events 10 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
1.3%
2/150 • Number of events 2 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
3.4%
5/147 • Number of events 8 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
5.3%
8/150 • Number of events 12 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Dizziness
|
7.5%
11/147 • Number of events 14 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
2.7%
4/150 • Number of events 4 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Dysaesthesia
|
4.8%
7/147 • Number of events 15 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
8.7%
13/150 • Number of events 22 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Dysgeusia
|
23.8%
35/147 • Number of events 43 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
22.7%
34/150 • Number of events 47 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Headache
|
8.2%
12/147 • Number of events 14 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
8.7%
13/150 • Number of events 18 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Neuropathy peripheral
|
45.6%
67/147 • Number of events 187 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
48.7%
73/150 • Number of events 217 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Paraesthesia
|
20.4%
30/147 • Number of events 82 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
22.0%
33/150 • Number of events 98 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
33.3%
49/147 • Number of events 132 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
26.0%
39/150 • Number of events 129 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Psychiatric disorders
Insomnia
|
5.4%
8/147 • Number of events 8 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
2.0%
3/150 • Number of events 3 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.8%
7/147 • Number of events 7 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
8.7%
13/150 • Number of events 14 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.2%
12/147 • Number of events 14 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
8.0%
12/150 • Number of events 12 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
15.6%
23/147 • Number of events 25 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
12.0%
18/150 • Number of events 19 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
7.5%
11/147 • Number of events 29 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
10.0%
15/150 • Number of events 21 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.4%
8/147 • Number of events 8 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
3.3%
5/150 • Number of events 5 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
|
Vascular disorders
Hypertension
|
7.5%
11/147 • Number of events 16 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
5.3%
8/150 • Number of events 10 • From screening until 30 days after the end of treatment visit which occurred after up to 6 months of treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place