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| ID | Type | Description | Link |
|---|---|---|---|
| H9H-MC-JBAV | Other Identifier | Eli Lilly and Company | |
| 2013-003235-30 | EudraCT Number |
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The purpose of this study is to investigate the effect of the study drug known as galunisertib in participants with myelodysplastic syndromes (MDS). Participants with different degrees of disease (very low, low, and intermediate risk) will be studied. The study treatment is expected to last about 6 months for each participant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase (ph) 2: Galunisertib + BSC | Experimental | Ph 2. 150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. |
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| Ph 3: Placebo + BSC | Placebo Comparator | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive BSC according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm. |
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| Ph 3: Galunisertib + BSC | Experimental | 150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Galunisertib | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Hematological Improvement (HI) | Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days). | Baseline through end of study treatment (24 weeks) |
| Percentage of Participants Who Are Transfusion-free or Have Hemoglobin (Hb) Increase ≥1.5 Grams/Deciliter Maintained for 8 Weeks During Phase 3 | Comparison of the percentage of participants with very low-, low-,and intermediate-risk MDS who were transfusion-free or had an increase ≥1.5 g/dL in hemoglobin (Hb) maintained for at least 8 weeks within the first 24 weeks of treatment with galunisertib plus best supportive care or placebo plus best supportive care and assessed by IPSS-R. The Phase 3 portion of this study was not conducted because efficacy level required in phase 2 to move forward to phase 3 was not achieved. | Baseline through end of study treatment (24 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Brief Fatigue Inventory (BFI) | The Brief Fatigue Inventory (BFI) is a brief participant-reported questionnaire that measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours. The severity of fatigue is assessed using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine. | Baseline, Follow up (final visit up to 24 months) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dresden | 01307 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31481511 | Derived | Santini V, Valcarcel D, Platzbecker U, Komrokji RS, Cleverly AL, Lahn MM, Janssen J, Zhao Y, Chiang A, Giagounidis A, Guba SC, Gueorguieva I, Girvan AC, da Silva Ferreira M, Bhagat TD, Pradhan K, Steidl U, Sridharan A, Will B, Verma A. Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes. Clin Cancer Res. 2019 Dec 1;25(23):6976-6985. doi: 10.1158/1078-0432.CCR-19-1338. Epub 2019 Sep 3. |
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Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
This is a single-arm study (Galunisertib at 150 milligram [mg]); the Galunisertib at 80 mg was considered exploratory and only conducted in parallel with the main study, at one site in Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Galunisertib at 150 mg | Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). |
| FG001 | Galunisertib at 80 mg | Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All participants (including the Galunisertib at 80 mg exploratory arm) who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Galunisertib at 150 mg | Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. |
| BG001 | Galunisertib at 80 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Hematological Improvement (HI) | Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days). | Participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through end of study treatment (24 weeks) |
|
Baseline through end of study treatment or death from any cause (Up to 2 years)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Galunisertib at 150 mg | Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
The response rate at interim analysis did not meet the predefined rate. The Phase 3 portion was not initiated and the sponsor decided on early discontinuation of the study at the conclusion of Phase 2.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C557799 | LY-2157299 |
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| Placebo | Drug | Administered orally |
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| Change From Baseline in EuroQol 5-Dimension 5 Level Instrument | EuroQol 5-Dimension 5 Level Instrument (EQ-5D-5L) was not conducted, trial terminated prior to Phase 3. No data collected. | Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days) |
| Percentage of Participants With Cytogenetic Response | Percentage of Participants with Cytogenetic Response with either complete or partial response. Complete cytogenetic response is the disappearance of the chromosomal abnormality without appearance of new ones. Partial cytogenetic response is at least 50% reduction of the chromosomal abnormality. | Baseline through end of study treatment (24 weeks) |
| Percentage of Participants Who Are Hospitalized (Resource Utilization) | Percentage of any participant with a hospitalization admission and discharge date on the same day are counted as a half-day in the duration of hospitalization. | Baseline through end of study treatment (24 weeks) |
| Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib | Population mean (between-participant coefficient variation [CV%]) apparent clearance. | Day 1 pre-dose & between 0.5 to 2 hours post dose; Day 14 pre-dose, between 0.5 to 2 & between 3 to 5 hours post dose; Days 15 & 16 (if logistically possible) between 0.5 to 2 hours post dose |
| Overall Survival (OS) | Overall survival is defined as the time from the date of first dose to the date of death from any cause. | Baseline to date of death from any cause (Up to 2 years) |
| Number of Participants With a Change in Bone Marrow Fibrosis Grading | Change from baseline in bone marrow fibrosis measured the number of participants with a change in bone marrow fibrosis grading (negative, mild, moderate, and severe). | Baseline, Cycle 6 (Cycle = 28 days) |
| Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Düsseldorf | 40479 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Jena | 07747 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lübeck | 23562 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ulm | 89081 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Westerstede | 26655 | Germany |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Florence | 50134 | Italy |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Novara | 28100 | Italy |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Rome | 00161 | Italy |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Barcelona | 08035 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Madrid | 28050 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Oviedo | 33011 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Salamanca | 37007 | Spain |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Valencia | 46026 | Spain |
| Progressive Disease |
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| Protocol Violation |
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| Withdrawal by Subject |
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Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
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| IPSS-R Prognostic Risk Score | Revised International Prognostic Scoring System (IPSS-R) is a screening tool used for MDS risk assessment. IPSS-R gives great weight to cytogenetic abnormalities and severity of cytopaenias, while reassigning the weighting for blast percentages. Score Categories: ≤1.5 Very Low, >1.5 - 3 Low, >3 - 4.5 Intermediate, >4.5 - 6 High, >6 Very High. The MDS Foundation website provides a calculator for determining IPSS-R scoring. | Count of Participants | Participants |
|
| OG001 | Arm: Galunisertib at 80 mg | Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles. |
|
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| Primary | Percentage of Participants Who Are Transfusion-free or Have Hemoglobin (Hb) Increase ≥1.5 Grams/Deciliter Maintained for 8 Weeks During Phase 3 | Comparison of the percentage of participants with very low-, low-,and intermediate-risk MDS who were transfusion-free or had an increase ≥1.5 g/dL in hemoglobin (Hb) maintained for at least 8 weeks within the first 24 weeks of treatment with galunisertib plus best supportive care or placebo plus best supportive care and assessed by IPSS-R. The Phase 3 portion of this study was not conducted because efficacy level required in phase 2 to move forward to phase 3 was not achieved. | Participants who received at least one dose of study drug during Phase 3. | Posted | Baseline through end of study treatment (24 weeks) |
|
|
| Secondary | Change From Baseline in Brief Fatigue Inventory (BFI) | The Brief Fatigue Inventory (BFI) is a brief participant-reported questionnaire that measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours. The severity of fatigue is assessed using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine. | Participants who received at least one dose of study drug. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Follow up (final visit up to 24 months) |
|
|
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| Secondary | Change From Baseline in EuroQol 5-Dimension 5 Level Instrument | EuroQol 5-Dimension 5 Level Instrument (EQ-5D-5L) was not conducted, trial terminated prior to Phase 3. No data collected. | Participants who received at least one dose of study drug during Phase 3. | Posted | Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days) |
|
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| Secondary | Percentage of Participants With Cytogenetic Response | Percentage of Participants with Cytogenetic Response with either complete or partial response. Complete cytogenetic response is the disappearance of the chromosomal abnormality without appearance of new ones. Partial cytogenetic response is at least 50% reduction of the chromosomal abnormality. | Participants who received at least one dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline through end of study treatment (24 weeks) |
|
|
|
| Secondary | Percentage of Participants Who Are Hospitalized (Resource Utilization) | Percentage of any participant with a hospitalization admission and discharge date on the same day are counted as a half-day in the duration of hospitalization. | Participants who received at least one dose of study drug. | Posted | Number | percentage of participants | Baseline through end of study treatment (24 weeks) |
|
|
|
| Secondary | Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib | Population mean (between-participant coefficient variation [CV%]) apparent clearance. | All participants who received at least one dose of study drug, regardless of dose, with evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/h) | Day 1 pre-dose & between 0.5 to 2 hours post dose; Day 14 pre-dose, between 0.5 to 2 & between 3 to 5 hours post dose; Days 15 & 16 (if logistically possible) between 0.5 to 2 hours post dose |
|
|
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| Secondary | Overall Survival (OS) | Overall survival is defined as the time from the date of first dose to the date of death from any cause. | Participants who received at least one dose of study drug excluding the exploratory participants. | Posted | Median | Full Range | days | Baseline to date of death from any cause (Up to 2 years) |
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| Secondary | Number of Participants With a Change in Bone Marrow Fibrosis Grading | Change from baseline in bone marrow fibrosis measured the number of participants with a change in bone marrow fibrosis grading (negative, mild, moderate, and severe). | Participants who received at least one dose of study drug and had both a baseline and postbaseline assessment excluding the exploratory participants. | Posted | Number | participants | Baseline, Cycle 6 (Cycle = 28 days) |
|
|
|
| 8 |
| 41 |
| 33 |
| 41 |
| EG001 | Galunisertib at 80 mg | Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). | 0 | 2 | 2 | 2 |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Crohn's disease | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Retroperitoneal haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Respiratory syncytial virus infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Tongue abscess | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Worst Fatigue at Follow-up |
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