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

Primary Purpose

Hematological Malignancies

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Study Part 1: KRP203

Study Part 2: KRP203 lower dose

Study Part 2: KRP203 higher dose

About this trial

This is an interventional prevention trial for Hematological Malignancies

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Study Part 1: KRP203

Study Part 2: lower KRP203 dose

Study Part 2: higher KRP203 dose

Arm Description

All patients to receive KRP203 for 111days

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Plasma Pharmacokinetics (PK) of KRP203: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)

Cmax Maximum (peak) blood drug concentration after drug administration [ng/mL]

Plasma Pharmacokinetics (PK) of KRP203: Time to reach the maximum concentration after drug administration

Tmax Time to reach maximum (peak) concentration [ng/mL]

GVHD-free, relapse free survival

occurence of GVHD, disease relaps and death will be assessed

GVHD-free, relapse free survival

occurence of GVHD, disease relaps and death will be assessed

Full Information

NCT ID

NCT01830010

First Posted

April 9, 2013

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01830010

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Completed

Study Start Date

June 28, 2013 (Actual)

Primary Completion Date

August 21, 2018 (Actual)

Study Completion Date

August 21, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematological Malignancies

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Study Part 1: KRP203

Arm Type

Experimental

Arm Description

All patients to receive KRP203 for 111days

Arm Title

Study Part 2: lower KRP203 dose

Arm Type

Experimental

Arm Description

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

Arm Title

Study Part 2: higher KRP203 dose

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Study Part 1: KRP203

Intervention Description

All subjects will receive KRP203 for 111 days

Intervention Type

Drug

Intervention Name(s)

Study Part 2: KRP203 lower dose

Intervention Type

Drug

Intervention Name(s)

Study Part 2: KRP203 higher dose

Primary Outcome Measure Information:

Title

Number of participants with Adverse Events as a Measure of safety

Description

Safety and tolerability of KRP203 in patients undergoing allogeneic hematopoetic stem cell transplant for hematological malignancies

Time Frame

111 days

Secondary Outcome Measure Information:

Title

Plasma Pharmacokinetics of KRP203: Area under the Plasma Concentration-time Curve (AUC)

Description

Time Frame

111 days

Title

Plasma Pharmacokinetics (PK) of KRP203: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)

Description

Cmax Maximum (peak) blood drug concentration after drug administration [ng/mL]

Time Frame

111 days

Title

Plasma Pharmacokinetics (PK) of KRP203: Time to reach the maximum concentration after drug administration

Description

Tmax Time to reach maximum (peak) concentration [ng/mL]

Time Frame

111 days

Title

GVHD-free, relapse free survival

Description

occurence of GVHD, disease relaps and death will be assessed

Time Frame

1 years post-transplant

Title

GVHD-free, relapse free survival

Description

occurence of GVHD, disease relaps and death will be assessed

Time Frame

2 years post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Paris

ZIP/Postal Code

75010

Country

France

Facility Name

Novartis Investigative Site

City

Regensburg

State/Province

Bavaria

ZIP/Postal Code

93053

Country

Germany

Facility Name

Novartis Investigative Site

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Novartis Investigative Site

City

Jena

ZIP/Postal Code

07740

Country

Germany

Facility Name

Novartis Investigative Site

City

Koeln

ZIP/Postal Code

50937

Country

Germany

Facility Name

Novartis Investigative Site

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Facility Name

Novartis Investigative Site

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Citations:

PubMed Identifier

36343893

Citation

Dertschnig S, Gergely P, Finke J, Schanz U, Holler E, Holtick U, Socie G, Medinger M, Passweg J, Teshima T, Stylianou C, Oehen S, Heim D, Bucher C. Mocravimod, a Selective Sphingosine-1-Phosphate Receptor Modulator, in Allogeneic Hematopoietic Stem Cell Transplantation for Malignancy. Transplant Cell Ther. 2023 Jan;29(1):41.e1-41.e9. doi: 10.1016/j.jtct.2022.10.029. Epub 2022 Nov 4.

Results Reference

derived

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17443

Description

Results for CKRP203A2105 can be found on the Novartis Clinical Trial Results Website

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=296

Description

A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

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

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

Hematological Malignancies

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial