A Study to Evaluate the Efficacy and Safety of Vismodegib in Combination with Ruxolitinib versus Placebo and Ruxolitinib in Patients with Intermediate- or High-Risk Myelofibrosis

A Phase Ib/III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of vismodegib in combination with ruxolitinib versus placebo and ruxolitinib in patients with intermediate- or high-risk myelofibrosis

Status

Active, not recruiting

Phases

Phase 1Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-001620-33-DE

Enrollment

104

Registered

2015-09-16

Start date

2015-11-12

Completion date

Unknown

Last updated

2017-07-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Intermediate- or high-risk myelofibrosis MedDRA version: 19.1 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Trade Name: Erivedge Pharmaceutical Form: Capsule, hard INN or Proposed INN: vismodegib CAS Number: 879085-55-9 Other descriptive name: VISMODEGIB Concentration unit: mg milligram(s) Concentration typ

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Pathologically confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF, according to the 2008 revised WHO criteria - Intermediate-1, intermediate-2, or high risk according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Dynamic International Prognostic Scoring System (DIPSS) Patients in the intermediate-1-risk group because of age alone (i.e., patients >= 65 years old with no other risk factors) are not eligible - In the investigator’s judgment, requires treatment for MF - Age >=18 years - Life expectancy of >=6 months - Peripheral blood blast count of 5 cm below the left costal margin - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 - All non-hematological adverse events must have resolved to NCI CTCAE Grade 30 milliliter/minute - Documented negative serum or urine pregnancy test for women of childbearing potential and use of two forms of acceptable contraception, including one highly effective contraceptive method plus a barrier method with spermicide. Contraception must be used while the patient is enrolled in the study and for 24 months after the last dose of vismodegib - For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partners to use an additional method of contraception during the study and for 2 months or 3 months after the last dose of vismodegib, depending on the country - Male patients must agree not to donate sperm during the study and for at least 2 months or 3 months after the last dose of vismodegib, depending on the country - All patients must agree not to donate blood or blood products during treatment and for 24 months after the last dose of vismodegib Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52

Exclusion criteria

Exclusion criteria: - Prior treatment with a Hedgehog (Hh) or Janus kinase (JAK) pathway inhibitor - Treatment with strong CYP3A4 inhibitors/inducers within 28 days prior to Day 1 - Prior therapy for the treatment of intermediate- or high-risk MF within 28 days prior to Day 1 - Prior splenectomy or splenic irradiation - Inadequate bone marrow reserve - Patients with any history of platelet counts of < 50,000/microliter or absolute neutrophil count of < 500/microliter, except during treatment for myeloproliferative neoplasm (MPN) or treatment with cytotoxic therapy for any other reason - Pregnant, lactating, or intending to become pregnant during the study - Patients who refuse to potentially receive blood products and/or have a severe hypersensitivity to blood products - Planned allogeneic bone marrow transplant during the study - Known history of HIV - Chronic active or acute viral hepatitis A, B or C infection - Patients with suspected active or latent tuberculosis - History of other malignancy that could affect compliance with the protocol or interpretation of results - Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 28 days prior to Day 1

Design outcomes

Primary

Measure	Time frame
Main Objective: 1. To evaluate the efficacy of vismodegib plus ruxolitinib compared with ruxolitinib plus placebo in patients with intermediate- or high-risk myelofibrosis (MF), as measured by spleen response rate at Week 24, determined by an Independent Review Committee (IRC) 2. To evaluate the efficacy of vismodegib plus ruxolitinib compared with ruxolitinib plus placebo in patients with intermediate- or high-risk MF, as measured by response rate (complete remission [CR] and partial remission [PR]) at Week 24, determined by an IRC;Secondary Objective: 1.To evaluate the efficacy of vismodegib plus ruxolitinib compared to placebo plus ruxolitinib measured by •Spleen response rate at Weeks 24 and 48 •Response rate, defined as CR and PR at Weeks 24 and 48 •Overall response rate (ORR) at Weeks 24 and 48 •Anemia response rate at Weeks 24 and 48 •Symptom improvement at Weeks 24 and 48 •Duration of overall response (DOR) •Improvement in bone marrow fibrosis at Weeks 24 and 48 •Progression-free survival (PFS) •Fatigue improvement at Weeks 24 and 48 •Other symptom and impact improvements, Function and health-related quality of life improvement at Weeks 24 and 48 •Overall survival (OS) 2.To evaluate the safety of vismodegib plus ruxolitinib compared with ruxolitinib plus placebo in patients with intermediate or high-risk MF as evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), V4.0 3.To characterize the pharmacokinetics of vismodegib in patients with intermediate or high-risk MF ;Primary end point(s): 1.Spleen response rate at Week 24, as determined by an IRC using IWG-MRT revised response criteria 2.Response rate (PR and CR) at Week 24, as determined by an IRC using IWG-MRT revised response criteria ;Timepoint(s) of evaluation of this end point: 1-2: Week 24	—

Measure

Time frame

Main Objective: 1. To evaluate the efficacy of vismodegib plus ruxolitinib compared with ruxolitinib plus placebo in patients with intermediate- or high-risk myelofibrosis (MF), as measured by spleen response rate at Week 24, determined by an Independent Review Committee (IRC) 2. To evaluate the efficacy of vismodegib plus ruxolitinib compared with ruxolitinib plus placebo in patients with intermediate- or high-risk MF, as measured by response rate (complete remission [CR] and partial remission [PR]) at Week 24, determined by an IRC;Secondary Objective: 1.To evaluate the efficacy of vismodegib plus ruxolitinib compared to placebo plus ruxolitinib measured by •Spleen response rate at Weeks 24 and 48 •Response rate, defined as CR and PR at Weeks 24 and 48 •Overall response rate (ORR) at Weeks 24 and 48 •Anemia response rate at Weeks 24 and 48 •Symptom improvement at Weeks 24 and 48 •Duration of overall response (DOR) •Improvement in bone marrow fibrosis at Weeks 24 and 48 •Progression-free survival (PFS) •Fatigue improvement at Weeks 24 and 48 •Other symptom and impact improvements, Function and health-related quality of life improvement at Weeks 24 and 48 •Overall survival (OS) 2.To evaluate the safety of vismodegib plus ruxolitinib compared with ruxolitinib plus placebo in patients with intermediate or high-risk MF as evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), V4.0 3.To characterize the pharmacokinetics of vismodegib in patients with intermediate or high-risk MF ;Primary end point(s): 1.Spleen response rate at Week 24, as determined by an IRC using IWG-MRT revised response criteria 2.Response rate (PR and CR) at Week 24, as determined by an IRC using IWG-MRT revised response criteria ;Timepoint(s) of evaluation of this end point: 1-2: Week 24

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Secondary

Measure	Time frame
Secondary end point(s): 1.Spleen response rate, determined according to IWG-MRT revised response criteria at Week 48 by an IRC and at Weeks 24 and 48 by the investigator 2.Response rate (PR and CR), determined according to IWG-MRT revised response criteria at Week 48 by an IRC and at Weeks 24 and 48 by the investigator 3.ORR (CR, PR, and clinical improvement) at Weeks 24 and 48, as determined by an IRC and the investigator using IWG-MRT revised response criteria 4.Anemia response rate at Weeks 24 and 48, as determined by the investigator using IWG-MRT revised response criteria 5.Symptom response rate from baseline to Weeks 24 and 48 as measured on a weekly basis on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) diary 6.DOR, as determined by the investigator and an IRC using IWG-MRT revised response criteria or death from any cause during the study 7.Improvement in bone marrow fibrosis of at least one grade at Weeks 24 and 48, as determined by the investigator and independent pathology review using the European consensus grading system 8.PFS 9.Proportion of patients who achieve a >= 50% reduction in fatigue from baseline to Weeks 24 and 48 as measured on a weekly basis on the MPN-SAF TSS diary 10.Proportion of patients who achieve a >=50% reduction in other symptom and impact item scores from baseline to Weeks 24 and 48, as measured by the MPN-SAF 11.Proportion of patients who achieved a meaningful improvement on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) physical, role, social, and emotional function and health status/ health-related quality of life (HRQoL) scale scores from baseline to Weeks 24 and 48 12.OS 13.Incidence of adverse events 14.Incidence of serious adverse events and adverse events leading to vismodegib/placebo discontinuation or interruption 15.Changes in vital signs, physical findings, and in clinical laboratory results	—

Measure

Time frame

Secondary end point(s): 1.Spleen response rate, determined according to IWG-MRT revised response criteria at Week 48 by an IRC and at Weeks 24 and 48 by the investigator 2.Response rate (PR and CR), determined according to IWG-MRT revised response criteria at Week 48 by an IRC and at Weeks 24 and 48 by the investigator 3.ORR (CR, PR, and clinical improvement) at Weeks 24 and 48, as determined by an IRC and the investigator using IWG-MRT revised response criteria 4.Anemia response rate at Weeks 24 and 48, as determined by the investigator using IWG-MRT revised response criteria 5.Symptom response rate from baseline to Weeks 24 and 48 as measured on a weekly basis on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) diary 6.DOR, as determined by the investigator and an IRC using IWG-MRT revised response criteria or death from any cause during the study 7.Improvement in bone marrow fibrosis of at least one grade at Weeks 24 and 48, as determined by the investigator and independent pathology review using the European consensus grading system 8.PFS 9.Proportion of patients who achieve a >= 50% reduction in fatigue from baseline to Weeks 24 and 48 as measured on a weekly basis on the MPN-SAF TSS diary 10.Proportion of patients who achieve a >=50% reduction in other symptom and impact item scores from baseline to Weeks 24 and 48, as measured by the MPN-SAF 11.Proportion of patients who achieved a meaningful improvement on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) physical, role, social, and emotional function and health status/ health-related quality of life (HRQoL) scale scores from baseline to Weeks 24 and 48 12.OS 13.Incidence of adverse events 14.Incidence of serious adverse events and adverse events leading to vismodegib/placebo discontinuation or interruption 15.Changes in vital signs, physical findings, and in clinical laboratory results

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Countries

Canada, France, Germany, Italy, United States

Contacts

Public ContactTrial Information Support Line-TISL

F. Hoffmann-La Roche Ltd.

global.rochegenentechtrials@roche.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026