A Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of KRP203 in Patients Undergoing Stem Cell Transplant for Hematological Malignancies

Study Overview
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Brief Summary
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Two part study to evaluate the safety, tolerability, pharmacokinetics, and efficacy (in Part 2 only) of KRP203 in patients undergoing allogeneic hemopoietic stem cell transplant for hematological malignancies

Official Title
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A Two-part, Single- and Two Arm Randomized, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy (in Part 2 Only) of KRP203 in Patients Undergoing Stem Cell Transplant for Hematological Malignancies

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Drug: Study Part 1: KRP203
* Drug: Study Part 2: KRP203 lower dose
* Drug: Study Part 2: KRP203 higher dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients aged 18 to 65 years, inclusive Patients must have a hematological malignancy that as per standard medical practice requires myeloablative conditioning (including short term myeloablative reduced intensity conditioning) followed by allogeneic hematopoetic stem cell transplant Karnofsky Performance status ≥60%. Suitable stem cell source available according to the graft selection algorithm using T-cell replete peripheral stem cells as a graft source Exclusion Criteria: Resting heart rate below 55 Significant cardiac disease (such as arrhytmia, heart failure) or any significant condition which in the investigators opinion would make the patient ineligible Previous allogeneic HSCT Any drug required that is not compatible with KRP203 (e.g. beta-blockers or anti-thymocyte globulin)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Part 1: KRP203<br>All patients to receive KRP203 for 111days | Drug: Study Part 1: KRP203<br>* All subjects will receive KRP203 for 111 days<br>|
| Experimental: Study Part 2: lower KRP203 dose<br>in this treatment arm patients will receive the lower KRP203 dose for 111 days on top of the standard treatment with cyclosporine A and methotrexte for GVHD prophylaxis | Drug: Study Part 2: KRP203 lower dose<br> <br> |
| Experimental: Study Part 2: higher KRP203 dose<br>in this treatment arm patients will recieve the higher KRP203 dose for 111 days on top of standard treatment with tacrolimus and methotrexate for GVHD prophylaxis | Drug: Study Part 2: KRP203 higher dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events as a Measure of safety | Safety and tolerability of KRP203 in patients undergoing allogeneic hematopoetic stem cell transplant for hematological malignancies | 111 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetics of KRP203: Area under the Plasma Concentration-time Curve (AUC) | The main PK parameters will be determined in whole blood using non-compartmental methods. Pk parameters being measured are: AUCtau AUC during a dosing interval (tau) of 24 hours [h.ng/mL] , AUCtauR Molar ratios between KRP203-P and KRP203 based on Cmax or AUCtau | 111 days | 
| Plasma Pharmacokinetics (PK) of KRP203: Observed Maximum Plasma Concentration Following Drug Administration (Cmax) | Cmax Maximum (peak) blood drug concentration after drug administration [ng/mL] | 111 days | 
| Plasma Pharmacokinetics (PK) of KRP203: Time to reach the maximum concentration after drug administration | Tmax Time to reach maximum (peak) concentration [ng/mL] | 111 days | 
| GVHD-free, relapse free survival | occurence of GVHD, disease relaps and death will be assessed | 1 years post-transplant | 
| GVHD-free, relapse free survival | occurence of GVHD, disease relaps and death will be assessed | 2 years post transplant |