A Trial Measuring ART-123 Ability to Prevent Sensory Neuropathy in Unresectable mCRC Subjects w/Oxaliplatin-based Chemo

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of ART-123 on sensory symptoms of oxaliplatin-induced peripheral neuropathy (OIPN) in patients with unresectable metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy

Detailed Description
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To compare the efficacy and safety of ART-123 (low and high dose) to placebo on sensory symptoms of oxaliplatin-induced peripheral neuropathy (OIPN) in patients with unresectable metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-national, Multi-center, Parallel-group, Phase 2b Assessing ART-123's Effect on Preventing Sensory Symptoms of OIPN in Unresectable mCRC Subjects Receiving Oxaliplatin-containing Chemo

Conditions
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Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: thrombomodulin alfa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Unresectable metastatic colorectal cancer; pathologically confirmed adenocarcinoma of the colon or rectum ECOG performance status of 0 or 1 The most recent laboratory findings (including for liver and kidney) within 14 days prior to randomization remain within acceptable ranges Willingness of the patient and the sexual partner to use a highly effective contraceptive method during the course of the study Able to sufficiently understand the clinical study and give written informed consent Exclusion Criteria: Prior treatment history with nerve toxic chemotherapeutic agent Peripheral neuropathy or central nervous system damage Psychiatric disorder History of major hemorrhage High risk of hemorrhage History of other malignancies Active ulcer Patients using anti-coagulants and fibrinolytic drugs Active Hepatitis B, or known HBs antigen positive Prior treatment history with thrombomodulin alfa Administration of another investigational medicinal product within 30 days prior to randomization Patient is pregnant (positive urine human chorionic gonadotropin) or breastfeeding or intends to get pregnant during the Treatment period Patients otherwise deemed as inappropriate to participate in the study by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>Reconstituted lyophilized ART-123 with sterile water for injection administered by intravenous drip infusion over approximately 30 minutes on Day 1 of each chemotherapy cycle. | Drug: thrombomodulin alfa<br>* Weight based dose of reconstituted treatment administered through intravenous drip infusion on Day1 of each chemotherapy cycle<br>* Other names: ART-123;|
| Experimental: High Dose<br>Reconstituted lyophilized ART-123 with sterile water for injection administered by intravenous drip infusion over approximately 30 minutes on Day 1 of each chemotherapy cycle. | Drug: thrombomodulin alfa<br>* Weight based dose of reconstituted treatment administered through intravenous drip infusion on Day1 of each chemotherapy cycle<br>* Other names: ART-123;|
| Placebo Comparator: Placebo<br>Reconstituted lyophilized placebo with sterile water for injection administered by intravenous drip infusion over approximately 30 minutes on Day 1 of each chemotherapy cycle. | Drug: Placebo<br>* Weight based dose of reconstituted treatment administered through intravenous drip infusion on Day1 of each chemotherapy cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FACT/GOG-NTX-12 (4 items) Total Score at Cycle 9 | Change from baseline in total score of the first 4 items of the FACT/GOG-NTX-12 at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FACT/GOG-NTX-12 (4 items) Total Score at 9 Months | Change from baseline in total score of the first 4 items of the FACT/GOG-NTX-12 at 9 months | 9 months | 
| FACT/GOG-NTX-12 (4 items) Proportional Score at Cycle 9 (each cycle is 2 weeks) | Proportion of subjects scoring 3 or 4 in at least 1 of the first 4 items of the FACT/GOG-NTX-12 at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| FACT/GOG-NTX-12 (4 items) Cumulative Score at Cycle 9 | Cumulative incidence of scoring 3 or 4 in at least 1 of the first 4 items of the FACT/GOG-NTX-12 through Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| FACT/GOG-NTX-12 (12 items) Total Score at Cycle 9 | Change from baseline in total score of FACT/GOG-NTX-12 at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| NRS (Pain) Scores (feet) at Cycle 9 | Change from baseline score of NRS (Pain) in feet at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| NRS (Pain) Scores (hands) at Cycle 9 | Change from baseline score of NRS (Pain) in hands at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| Side Effect Questionnaire Score | Change from baseline score of Side effect questionnaire at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| CTCAE: Peripheral Sensory Neuropathy | Proportion of subjects with each Grade of CTCAE peripheral sensory neuropathy at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| CTCAE: Peripheral Motor Neuropathy | Proportion of subjects with each Grade of CTCAE peripheral motor neuropathy at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| mTCNS Score | Change from baseline in total score of mTCNS at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| Grooved Pegboard Change | Change from baseline score in the time to complete the Grooved Pegboard test with the non-dominant hand at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) | 
| EQ-5D-5L Change | Change from baseline in EQ-5D-5L index value at the end of Cycle 9 | Cycle 9 (each cycle is 2 weeks) |