Brentuximab Vedotin in Chinese Participants With Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL)
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT02939014
Collaborator
(none)
39
7
1
38.9
5.6
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of brentuximab vedotin as a single agent in Chinese participants with relapsed/refractory CD30+ Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The drug being tested in this study is called brentuximab vedotin. This study will look at efficacy, safety and PK of brentuximab vedotin in Chinese participants with relapsed/refractory CD30+ HL or sALCL.
The study will enroll approximately 30 patients. Participants will receive:
• Brentuximab vedotin 1.8 mg/kg
All participants will be administered IV infusion on Day 1 each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles.
This multi-center trial will be conducted in China only. The overall time to participate in this study is 3.5 years. Participants will make multiple visits to the clinic, and will be followed for overall survival (OS) every 12 weeks until death, withdrawal of consent, 18 months after end of treatment (EOT) or study closure, whichever occurs first.
Study Design
Study Type:
Interventional
Actual Enrollment
:
39 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Single-Arm, Open-label Study of Brentuximab Vedotin in Chinese Patients With Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL)
Actual Study Start Date
:
Nov 7, 2016
Actual Primary Completion Date
:
Aug 2, 2018
Actual Study Completion Date
:
Feb 3, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Brentuximab Vedotin 1.8 mg/kg Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles. |
Drug: Brentuximab Vedotin
Brentuximab vedotin IV infusion
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months)]
ORR is defined as the percentage of participants who have achieved complete remission (CR)=disappearance of all evidence of disease or partial remission (PR)=regression of greater than or equal to 50% of measurable disease and no new site by end of treatment (EOT) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)]
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug.
- Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events [First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)]
Clinical Laboratory tests included tests of Chemistry, Hematology and Urinalysis prespecified in the protocol. Abnormal laboratory values assessed by the investigator that lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be clinically significant changes from Baseline were recorded as Adverse Events. Neutropenia (pooled) includes preferred terms Neutropenia and Neutrophil count decreased.
- Number of Participants With Abnormal Vital Signs Reported as Adverse Events [First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)]
Vital signs included blood pressure in the sitting position, pulse rate, axillary temperature and weight. Abnormal vital sign values considered by the investigator to be clinically significant were recorded as Adverse Events.
Secondary Outcome Measures
- Complete Remission (CR) Rate [Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months)]
CR rate is defined as the percentage of participants who have achieved CR by EOT. CR is defined as disappearance of all evidence of disease per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
- Duration of Response (DOR) [Up to 3.2 years]
DOR is defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective tumor progression or death due to any cause, whichever occurs first. CR is defined as disappearance of all evidence of disease. PR is defined as regression of greater than or equal to 50% of measurable disease and no new sites.
- Progression Free Survival (PFS) [Up to 3.2 years]
PFS is defined as the time from the start of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
- Overall Survival (OS) [Up to 3.2 years]
Overall survival is defined as the time from the start of treatment to the date of death.
- B Symptom Resolution Rate [Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months)]
B Symptom Resolution Rate is defined as the percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss >10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.
- Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) [Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) [Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) [Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC [Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb [Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE [Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC [Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb [Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE [Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose]
- Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin [Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression, death or end of treatment (approximately 12 months)]
Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test to determine ATA titers. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-baseline confirmed ATA positive responses) and by nATA status. The number of participants in each baseline ATA and post-baseline ATA categories are reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have histologically confirmed CD30+ hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). Immunohistochemistry or flow cytometry may be performed on either original diagnostic biopsy material or biopsy of relapsed disease, and pathology reports of CD30+ or their copies should be retained at the site.
-
With CD30+ HL or sALCL who have relapsed from or are refractory to previous treatments.
-
Fluorodeoxyglucose (FDG)- positron emission tomography (PET) positive and measurable disease of at least 1.5 cm in the longest diameter by computed tomography (CT), as assessed by the site.
-
Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
-
Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
-
Must have the following required screening laboratory data. Participants must not have received recombinant granulocyte-colony stimulating factor (G-CSF) or platelet transfusion within 1 week before the screening hematology assessment.
-
Absolute neutrophil count ≥1500/μL.
-
Platelet count ≥75,000/μL.
-
Serum bilirubin level ≤1.5 times the upper limit of the normal range (ULN).
-
Serum creatinine level ≤1.5 times the ULN.
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the ULN.
-
Survival for 3 or more months must be expected.
Exclusion Criteria:
-
With current diagnosis of primary cutaneous anaplastic large cell lymphoma (ALCL) (participants with other organ involvement who have transformed to sALCL are eligible).
-
With any active viral, bacterial, or fungal infection within 2 weeks before the first dose of brentuximab vedotin.
-
With cardiac failure categorized as Class III or IV according to the New York Heart Association criteria, uncontrolled coronary artery disease or uncontrolled arrhythmia despite of appropriate medical therapy, or a history of myocardial infarction within 6 months before the first dose of brentuximab vedotin.
-
With uncontrolled diabetes mellitus.
-
Peripheral neuropathy ≥Grade 2.
-
With a history of another malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit:
-
Nonmelanoma skin cancer.
-
Curatively treated localized prostate cancer.
-
Cervical carcinoma in situ.
-
With known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML).
-
With a positive result in the screening test for human immunodeficiency virus (HIV) antibody.
-
Known hepatitis B virus (HBV) surface antigen seropositive or positive hepatitis C virus (HCV) antibody. Note: participants who have positive HBV core antibody can be enrolled but must have an undetectable HBV viral load.
-
With a history of liver fibrosis or cirrhosis and clinical signs and symptoms indicating liver fibrosis or cirrhosis.
-
Have received autologous stem cell transplantation (auto-SCT) within 12 weeks before the first dose of brentuximab vedotin.
-
With history of allogeneic stem cell transplantation (allo-SCT).
-
Have received treatment for malignancies (including radiation, chemotherapy, and hormone therapy) within 4 weeks before the first dose of brentuximab vedotin and participants who have received treatment for malignancies with biologics (including molecular target drug) or radioisotopic therapy within 12 weeks before the first dose of brentuximab vedotin.
-
Have unresolved toxicity higher than Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03) attributed to any prior therapy/procedure (excluding alopecia or non-clinically significant and asymptomatic laboratory abnormalities).
-
Have received systemic corticosteroids at doses greater than the equivalent of 20 mg/day of prednisone within 1 week before the first dose of brentuximab vedotin.
-
Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of the safety and toxicity of the prescribed regimens.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Cancer Hospital | Beijing | Beijing | China | 100142 |
| 2 | Peking University Third Hospital | Beijing | Beijing | China | 100191 |
| 3 | Sun Yat-san University Cancer Center | Guangzhou | Guangdong | China | 510060 |
| 4 | Jiangsu Cancer Hospital | Nanjing | Jiangsu | China | 210009 |
| 5 | Jiangsu Province People's Hospital | Nanjing | Jiangsu | China | 210029 |
| 6 | The First Hospital of Jilin University | Changchun | Jilin | China | |
| 7 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | 200010 |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02939014
Other Study ID Numbers:
- C25010
- U1111-1184-1838
First Posted:
Oct 19, 2016
Last Update Posted:
Feb 24, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Takeda
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 7 investigative sites in China. The study was conducted from 07 November 2016 to 3 February 2020. |
|---|---|
| Pre-assignment Detail | Participants with a diagnosis of Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL) were enrolled to receive brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, Day 1 of every 3-week cycle. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Period Title: Overall Study | ||
| STARTED | 30 | 9 |
| COMPLETED | 25 | 6 |
| NOT COMPLETED | 5 | 3 |
Baseline Characteristics
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) | Total |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). | Total of all reporting groups |
| Overall Participants | 30 | 9 | 39 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
31.9
(8.91)
|
41.1
(15.28)
|
34.0
(11.19)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
13
43.3%
|
2
22.2%
|
15
38.5%
|
| Male |
17
56.7%
|
7
77.8%
|
24
61.5%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Not Hispanic or Latino |
30
100%
|
9
100%
|
39
100%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
30
100%
|
9
100%
|
39
100%
|
| Region of Enrollment (Count of Participants) | |||
| China |
30
100%
|
9
100%
|
39
100%
|
Outcome Measures
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as the percentage of participants who have achieved complete remission (CR)=disappearance of all evidence of disease or partial remission (PR)=regression of greater than or equal to 50% of measurable disease and no new site by end of treatment (EOT) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Time Frame | Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent-to-Treat (mITT) Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Number (95% Confidence Interval) [percentage of participants] |
70.0
233.3%
|
66.7
741.1%
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| Description | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug. |
| Time Frame | First dose of study drug up to 30 days after last dose of study drug (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Count of Participants [Participants] |
30
100%
|
9
100%
|
| Title | Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events |
|---|---|
| Description | Clinical Laboratory tests included tests of Chemistry, Hematology and Urinalysis prespecified in the protocol. Abnormal laboratory values assessed by the investigator that lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be clinically significant changes from Baseline were recorded as Adverse Events. Neutropenia (pooled) includes preferred terms Neutropenia and Neutrophil count decreased. |
| Time Frame | First dose of study drug up to 30 days after last dose of study drug (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Alanine aminotransferase increased |
18
60%
|
6
66.7%
|
| Aspartate aminotransferase increased |
17
56.7%
|
6
66.7%
|
| Gamma-glutamyltransferase increased |
3
10%
|
4
44.4%
|
| Blood bilirubin increased |
0
0%
|
2
22.2%
|
| Reticulocyte count decreased |
9
30%
|
2
22.2%
|
| Reticulocyte count increased |
6
20%
|
1
11.1%
|
| Haemoglobin decreased |
1
3.3%
|
1
11.1%
|
| Reticulocyte percentage increased |
1
3.3%
|
0
0%
|
| White blood cell count decreased |
4
13.3%
|
3
33.3%
|
| Lymphocyte count decreased |
5
16.7%
|
0
0%
|
| Lymphocyte percentage decreased |
2
6.7%
|
0
0%
|
| Lymphocyte count increased |
0
0%
|
1
11.1%
|
| Lymphocyte percentage increased |
0
0%
|
1
11.1%
|
| Monocyte count increased |
0
0%
|
1
11.1%
|
| Neutrophil count increased |
0
0%
|
1
11.1%
|
| Neutrophil percentage decreased |
1
3.3%
|
0
0%
|
| White blood cell count increased |
0
0%
|
1
11.1%
|
| Platelet count decreased |
2
6.7%
|
2
22.2%
|
| Blood uric acid increased |
2
6.7%
|
1
11.1%
|
| Blood glucose increased |
1
3.3%
|
1
11.1%
|
| Blood albumin decreased |
0
0%
|
1
11.1%
|
| Protein total decreased |
0
0%
|
1
11.1%
|
| Blood creatinine increased |
1
3.3%
|
1
11.1%
|
| Blood urea decreased |
0
0%
|
1
11.1%
|
| Blood urea increased |
0
0%
|
1
11.1%
|
| Blood lactate dehydrogenase increased |
0
0%
|
2
22.2%
|
| Blood alkaline phosphatase increased |
0
0%
|
1
11.1%
|
| Blood cholesterol increased |
0
0%
|
1
11.1%
|
| Blood calcium decreased |
0
0%
|
1
11.1%
|
| Blood calcium increased |
0
0%
|
1
11.1%
|
| Blood chloride decreased |
0
0%
|
1
11.1%
|
| Blood phosphorus decreased |
0
0%
|
1
11.1%
|
| Blood potassium decreased |
0
0%
|
1
11.1%
|
| Blood triglycerides increased |
0
0%
|
1
11.1%
|
| Glucose urine present |
1
3.3%
|
0
0%
|
| Leukopenia |
15
50%
|
2
22.2%
|
| Anaemia |
12
40%
|
3
33.3%
|
| Hyperuricaemia |
4
13.3%
|
2
22.2%
|
| Hypertriglyceridaemia |
2
6.7%
|
2
22.2%
|
| Hypokalaemia |
3
10%
|
2
22.2%
|
| Blood creatine phosphokinase increased |
1
3.3%
|
1
11.1%
|
| Total bile acids increased |
0
0%
|
2
22.2%
|
| Alpha hydroxybutyrate dehydrogenase increased |
0
0%
|
1
11.1%
|
| Blood magnesium decreased |
0
0%
|
1
11.1%
|
| High density lipoprotein decreased |
0
0%
|
1
11.1%
|
| Hypercalcaemia |
0
0%
|
1
11.1%
|
| Hyperglycaemia |
1
3.3%
|
0
0%
|
| Hypoalbuminaemia |
0
0%
|
1
11.1%
|
| Hypocalcaemia |
0
0%
|
1
11.1%
|
| Hyponatraemia |
1
3.3%
|
0
0%
|
| Lipoprotein (a) increased |
0
0%
|
1
11.1%
|
| Low density lipoprotein increased |
0
0%
|
1
11.1%
|
| Monocytosis |
0
0%
|
1
11.1%
|
| Red blood cell sedimentation rate increased |
1
3.3%
|
0
0%
|
| Thrombocytopenia |
1
3.3%
|
0
0%
|
| Neutropenia (Pooled) |
19
63.3%
|
5
55.6%
|
| Title | Number of Participants With Abnormal Vital Signs Reported as Adverse Events |
|---|---|
| Description | Vital signs included blood pressure in the sitting position, pulse rate, axillary temperature and weight. Abnormal vital sign values considered by the investigator to be clinically significant were recorded as Adverse Events. |
| Time Frame | First dose of study drug up to 30 days after last dose of study drug (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Weight increased |
4
13.3%
|
2
22.2%
|
| Weight decreased |
1
3.3%
|
2
22.2%
|
| Title | Complete Remission (CR) Rate |
|---|---|
| Description | CR rate is defined as the percentage of participants who have achieved CR by EOT. CR is defined as disappearance of all evidence of disease per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Time Frame | Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Number (95% Confidence Interval) [percentage of participants] |
20.0
66.7%
|
55.6
617.8%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR is defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective tumor progression or death due to any cause, whichever occurs first. CR is defined as disappearance of all evidence of disease. PR is defined as regression of greater than or equal to 50% of measurable disease and no new sites. |
| Time Frame | Up to 3.2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. Only responders were analyzed for this outcome measure. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 21 | 6 |
| Median (95% Confidence Interval) [months] |
12.0
|
NA
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from the start of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. |
| Time Frame | Up to 3.2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Median (95% Confidence Interval) [months] |
13.5
|
23.2
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival is defined as the time from the start of treatment to the date of death. |
| Time Frame | Up to 3.2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population included all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | B Symptom Resolution Rate |
|---|---|
| Description | B Symptom Resolution Rate is defined as the percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss >10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period. |
| Time Frame | Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the mITT Population, all participants who had measurable lesions at baseline and received at least 1 dose of brentuximab vedotin, who had lymphoma-related B symptoms at baseline. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 2 | 2 |
| Number (95% Confidence Interval) [percentage of participants] |
50.0
166.7%
|
100.00
1111.1%
|
| Title | Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) |
|---|---|
| Description | |
| Time Frame | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK)-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Cycle 1 |
36.9504
(9.90360)
|
| Cycle 2 |
32.4341
(5.83197)
|
| Title | Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) |
|---|---|
| Description | |
| Time Frame | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Cycle 1 |
38.2293
(7.95483)
|
| Cycle 2 |
39.9859
(12.43445)
|
| Title | Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) |
|---|---|
| Description | |
| Time Frame | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Cycle 1 |
5.1623
(3.69893)
|
| Cycle 2 |
3.6218
(2.89331)
|
| Title | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC |
|---|---|
| Description | |
| Time Frame | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Cycle 1 |
0.0576
|
| Cycle 2 |
0.0528
|
| Title | Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb |
|---|---|
| Description | |
| Time Frame | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Cycle 1 |
0.0653
|
| Cycle 2 |
0.0660
|
| Title | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE |
|---|---|
| Description | |
| Time Frame | Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Cycle 1 |
2.0729
|
| Cycle 2 |
2.9785
|
| Title | AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC |
|---|---|
| Description | |
| Time Frame | Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the PK-evaluable Populations, participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist, with data available for analysis. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 38 |
| Mean (Standard Deviation) [day*ug/mL] |
79.9951
(19.59116)
|
| Title | AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb |
|---|---|
| Description | |
| Time Frame | Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Mean (Standard Deviation) [day*ug/mL] |
168.6618
(41.62840)
|
| Title | AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE |
|---|---|
| Description | |
| Time Frame | Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable Population includes participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by the clinical pharmacologist. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles includes all participants. |
| Measure Participants | 39 |
| Mean (Standard Deviation) [day*ug/mL] |
36.8625
(22.79816)
|
| Title | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin |
|---|---|
| Description | Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test to determine ATA titers. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-baseline confirmed ATA positive responses) and by nATA status. The number of participants in each baseline ATA and post-baseline ATA categories are reported. |
| Time Frame | Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression, death or end of treatment (approximately 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Immunogenicity Population included participants who received at least 1 dose of brentuximab vedotin and had ATA status assessment at baseline, and at least 1 postbaseline sample. Number analyzed is the number of participants with data available. |
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). |
| Measure Participants | 30 | 9 |
| Baseline ATA Negative |
29
96.7%
|
9
100%
|
| Baseline ATA Negative, ATA Negative |
21
70%
|
8
88.9%
|
| Baseline ATA Negative, Transiently ATA Positive |
7
23.3%
|
1
11.1%
|
| Baseline ATA Negative, Persistently ATA Positive |
1
3.3%
|
0
0%
|
| Baseline ATA Negative, nATA Negative |
0
0%
|
0
0%
|
| Baseline ATA Negative, nATA Positive |
8
26.7%
|
1
11.1%
|
| Baseline ATA Positive |
1
3.3%
|
0
0%
|
| Baseline ATA Positive, ATA Negative |
0
0%
|
|
| Baseline ATA Positive, Transiently ATA Positive |
0
0%
|
|
| Baseline ATA Positive, Persistently ATA Positive |
1
3.3%
|
|
| Baseline ATA Positive, nATA Negative |
0
0%
|
|
| Baseline ATA Positive, nATA Positive |
1
3.3%
|
Adverse Events
| Time Frame | All-Cause Mortality: up to 3.2 years; Serious and Other Adverse Events: First dose of study drug up to 30 days post last dose of study drug (up to 12 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||
| Arm/Group Title | Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) | ||
| Arm/Group Description | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL). | Brentuximab vedotin 1.8 mg/kg, IV, infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles in participants with Relapsed/Refractory Systemic Anaplastic Large Cell Lymphoma (sALCL). | ||
All Cause Mortality |
||||
| Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/30 (13.3%) | 3/9 (33.3%) | ||
Serious Adverse Events |
||||
| Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Gastrointestinal disorders | ||||
| Large intestine polyp | 0/30 (0%) | 1/9 (11.1%) | ||
| Infections and infestations | ||||
| Lung infection | 1/30 (3.3%) | 0/9 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Brentuximab Vedotin 1.8 mg/kg (HL) | Brentuximab Vedotin 1.8 mg/kg (sALCL) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 30/30 (100%) | 9/9 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 15/30 (50%) | 2/9 (22.2%) | ||
| Anaemia | 12/30 (40%) | 3/9 (33.3%) | ||
| Neutropenia | 19/30 (63.3%) | 5/9 (55.6%) | ||
| Monocytosis | 0/30 (0%) | 1/9 (11.1%) | ||
| Lymphadenopathy | 0/30 (0%) | 1/9 (11.1%) | ||
| Cardiac disorders | ||||
| Palpitations | 2/30 (6.7%) | 0/9 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 8/30 (26.7%) | 3/9 (33.3%) | ||
| Nausea | 8/30 (26.7%) | 0/9 (0%) | ||
| Vomiting | 4/30 (13.3%) | 1/9 (11.1%) | ||
| Retching | 0/30 (0%) | 1/9 (11.1%) | ||
| Abdominal distension | 4/30 (13.3%) | 0/9 (0%) | ||
| Flatulence | 3/30 (10%) | 0/9 (0%) | ||
| Dyspepsia | 4/30 (13.3%) | 0/9 (0%) | ||
| Abdominal pain upper | 3/30 (10%) | 0/9 (0%) | ||
| Gastrooesophageal reflux disease | 3/30 (10%) | 0/9 (0%) | ||
| Abdominal discomfort | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Gingival bleeding | 0/30 (0%) | 1/9 (11.1%) | ||
| General disorders | ||||
| Malaise | 6/30 (20%) | 1/9 (11.1%) | ||
| Asthenia | 4/30 (13.3%) | 0/9 (0%) | ||
| Pyrexia | 6/30 (20%) | 4/9 (44.4%) | ||
| Pain | 3/30 (10%) | 0/9 (0%) | ||
| Chest discomfort | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 9/30 (30%) | 2/9 (22.2%) | ||
| Nasopharyngitis | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Tonsillitis | 0/30 (0%) | 1/9 (11.1%) | ||
| Herpes zoster | 2/30 (6.7%) | 1/9 (11.1%) | ||
| Nail infection | 0/30 (0%) | 1/9 (11.1%) | ||
| Gastroenteritis | 0/30 (0%) | 1/9 (11.1%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 18/30 (60%) | 6/9 (66.7%) | ||
| Aspartate aminotransferase increased | 17/30 (56.7%) | 6/9 (66.7%) | ||
| Gamma-glutamyltransferase increased | 3/30 (10%) | 4/9 (44.4%) | ||
| Blood bilirubin increased | 0/30 (0%) | 2/9 (22.2%) | ||
| Reticulocyte count decreased | 9/30 (30%) | 2/9 (22.2%) | ||
| Reticulocyte count increased | 6/30 (20%) | 1/9 (11.1%) | ||
| Haemoglobin decreased | 1/30 (3.3%) | 1/9 (11.1%) | ||
| White blood cell count decreased | 4/30 (13.3%) | 3/9 (33.3%) | ||
| Lymphocyte count decreased | 5/30 (16.7%) | 0/9 (0%) | ||
| Lymphocyte percentage decreased | 2/30 (6.7%) | 0/9 (0%) | ||
| Lymphocyte count increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Lymphocyte percentage increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Monocyte count increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Neutrophil count increased | 0/30 (0%) | 1/9 (11.1%) | ||
| White blood cell count increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Weight increased | 4/30 (13.3%) | 2/9 (22.2%) | ||
| Weight decreased | 1/30 (3.3%) | 2/9 (22.2%) | ||
| Platelet count decreased | 2/30 (6.7%) | 2/9 (22.2%) | ||
| Blood uric acid increased | 2/30 (6.7%) | 1/9 (11.1%) | ||
| Retinol binding protein increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood glucose increased | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Blood albumin decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Protein total decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood creatinine increased | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Blood urea decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood urea increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood creatine phosphokinase increased | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Alpha hydroxybutyrate dehydrogenase increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood lactate dehydrogenase increased | 0/30 (0%) | 2/9 (22.2%) | ||
| Blood alkaline phosphatase increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood cholesterol increased | 0/30 (0%) | 1/9 (11.1%) | ||
| High density lipoprotein decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Lipoprotein (a) increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Low density lipoprotein increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Electrocardiogram abnormal | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood calcium decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood calcium increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood chloride decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood magnesium decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood phosphorus decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood potassium decreased | 0/30 (0%) | 1/9 (11.1%) | ||
| Blood triglycerides increased | 0/30 (0%) | 1/9 (11.1%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperuricaemia | 4/30 (13.3%) | 2/9 (22.2%) | ||
| Hypertriglyceridaemia | 2/30 (6.7%) | 2/9 (22.2%) | ||
| Hypokalaemia | 3/30 (10%) | 0/9 (0%) | ||
| Hypercalcaemia | 0/30 (0%) | 1/9 (11.1%) | ||
| Hypocalcaemia | 0/30 (0%) | 1/9 (11.1%) | ||
| Hypoalbuminaemia | 0/30 (0%) | 1/9 (11.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Muscle spasms | 2/30 (6.7%) | 0/9 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 0/30 (0%) | 1/9 (11.1%) | ||
| Nervous system disorders | ||||
| Peripheral sensory neuropathy | 9/30 (30%) | 2/9 (22.2%) | ||
| Neuropathy peripheral | 0/30 (0%) | 2/9 (22.2%) | ||
| Headache | 8/30 (26.7%) | 0/9 (0%) | ||
| Hypoaesthesia | 4/30 (13.3%) | 2/9 (22.2%) | ||
| Dizziness | 5/30 (16.7%) | 1/9 (11.1%) | ||
| Psychiatric disorders | ||||
| Insomnia | 2/30 (6.7%) | 0/9 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 3/30 (10%) | 2/9 (22.2%) | ||
| Interstitial lung disease | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Epistaxis | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Oropharyngeal pain | 1/30 (3.3%) | 1/9 (11.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 8/30 (26.7%) | 1/9 (11.1%) | ||
| Rash | 3/30 (10%) | 2/9 (22.2%) | ||
| Night sweats | 3/30 (10%) | 0/9 (0%) | ||
| Hyperhidrosis | 0/30 (0%) | 1/9 (11.1%) | ||
| Dermatitis allergic | 2/30 (6.7%) | 1/9 (11.1%) | ||
| Urticaria | 2/30 (6.7%) | 1/9 (11.1%) | ||
| Pruritus | 2/30 (6.7%) | 0/9 (0%) | ||
| Papule | 0/30 (0%) | 1/9 (11.1%) | ||
| Psoriasis | 0/30 (0%) | 1/9 (11.1%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02939014
Other Study ID Numbers:
- C25010
- U1111-1184-1838
First Posted:
Oct 19, 2016
Last Update Posted:
Feb 24, 2021
Last Verified:
Feb 1, 2021