Clinical Trial Results:
A Phase 3 Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Rozanolixizumab in Adult Study Participants With Persistent or Chronic Primary Immune Thrombocytopenia (ITP)
|
Summary
|
|
EudraCT number |
2019-000884-26 |
Trial protocol |
PL BG HU BE CZ AT ES NL GB FR GR IT HR RO |
Global end of trial date |
27 Apr 2022
|
|
Results information
|
|
Results version number |
v1 |
This version publication date |
05 May 2023
|
First version publication date |
05 May 2023
|
Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
TP0003
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04200456 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
UCB Biopharma SRL
|
||
Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, 1070
|
||
Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
|
||
Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
05 Oct 2022
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
21 Mar 2022
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
27 Apr 2022
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Demonstrate the clinical efficacy of rozanolixizumab in maintenance treatment in study participants with primary immune thrombocytopenia
|
||
Protection of trial subjects |
During the conduct of the study all participants were closely monitored.
|
||
Background therapy |
Background therapy as permitted in the protocol. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
31 Jan 2020
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 1
|
||
Country: Number of subjects enrolled |
Georgia: 4
|
||
Country: Number of subjects enrolled |
Hungary: 3
|
||
Country: Number of subjects enrolled |
Italy: 1
|
||
Country: Number of subjects enrolled |
Japan: 3
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 1
|
||
Country: Number of subjects enrolled |
Moldova, Republic of: 2
|
||
Country: Number of subjects enrolled |
Poland: 10
|
||
Country: Number of subjects enrolled |
Russian Federation: 1
|
||
Country: Number of subjects enrolled |
Taiwan: 1
|
||
Country: Number of subjects enrolled |
Ukraine: 5
|
||
Country: Number of subjects enrolled |
United Kingdom: 1
|
||
Worldwide total number of subjects |
33
|
||
EEA total number of subjects |
15
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
29
|
||
From 65 to 84 years |
4
|
||
85 years and over |
0
|
||
|
||||||||||||||||||||||||||||
|
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
The study started to enroll study participants in Jan 2020 and terminated in April 2022. | |||||||||||||||||||||||||||
|
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
Participant Flow refers to the Randomized Set. | |||||||||||||||||||||||||||
|
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||
|
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
|
Arm title
|
Placebo | |||||||||||||||||||||||||||
Arm description |
Participants received a fixed-unit starting dose of placebo subcutaneous (sc) infusion matched to rozanolixizumab Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of placebo sc infusion matched to rozanolixizumab Dose B every 2 weeks until Week 23. Participants were followed up to a maximum of Week 31. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received placebo at prespecified time points.
|
|||||||||||||||||||||||||||
|
Arm title
|
Rozanolixizumab | |||||||||||||||||||||||||||
Arm description |
Participants received a fixed-unit starting dose of rozanolixizumab sc infusion equivalent to Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of rozanolixizumab sc infusion equivalent to Dose B every 2 weeks until Week 23. After protocol amendment 3, the starting dose was removed and the frequency of administration of the Dose B was changed to weekly. Participants were followed up to a maximum of Week 31. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Rozanolixizumab
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
UCB7665
|
|||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received rozanolixizumab at prespecified time points.
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received a fixed-unit starting dose of placebo subcutaneous (sc) infusion matched to rozanolixizumab Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of placebo sc infusion matched to rozanolixizumab Dose B every 2 weeks until Week 23. Participants were followed up to a maximum of Week 31. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rozanolixizumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received a fixed-unit starting dose of rozanolixizumab sc infusion equivalent to Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of rozanolixizumab sc infusion equivalent to Dose B every 2 weeks until Week 23. After protocol amendment 3, the starting dose was removed and the frequency of administration of the Dose B was changed to weekly. Participants were followed up to a maximum of Week 31. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
Participants received a fixed-unit starting dose of placebo subcutaneous (sc) infusion matched to rozanolixizumab Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of placebo sc infusion matched to rozanolixizumab Dose B every 2 weeks until Week 23. Participants were followed up to a maximum of Week 31. | ||
Reporting group title |
Rozanolixizumab
|
||
Reporting group description |
Participants received a fixed-unit starting dose of rozanolixizumab sc infusion equivalent to Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of rozanolixizumab sc infusion equivalent to Dose B every 2 weeks until Week 23. After protocol amendment 3, the starting dose was removed and the frequency of administration of the Dose B was changed to weekly. Participants were followed up to a maximum of Week 31. | ||
|
|||||||||||||
End point title |
Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50x10^9/L, for at least 8 out of 12 weeks during the last 12 weeks [1] | ||||||||||||
End point description |
Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50×10^9/L, for at least 8 out of 12 weeks during the last 12 weeks were reported. Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
During the last 12 weeks (Week 13 to Week 25)
|
||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only Descriptive analysis was planned to be reported for this endpoint. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Cumulative number of weeks with Clinically Meaningful Platelet Response of ≥50×10^9/L over the 24-week Treatment Period | ||||||||||||
End point description |
Total number of weeks with platelet counts ≥50×10^9/L over the 24-week Treatment Period of the study (Week 1 to Week 25) were reported. Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 1 up to Week 25
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to first Clinically Meaningful Platelet Response of ≥50×10^9/L: time from starting treatment to achievement of first response of ≥50×10^9/L | ||||||||||||
End point description |
Time from starting treatment to achievement of first clinically meaningful platelet response of ≥50×10^9/L was defined as date of first clinically meaningful response - date of first treatment + 1. Median was calculated based upon the Kaplan-Meier estimate. Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated. -999 and 999 indicate not available because no formal analysis was carried out as the program was terminated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Time from starting treatment to achievement of first response of ≥50×10^9/L (up to Week 25)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants with Clinically Meaningful Platelet Response of ≥50×10^9/L by Day 8 | ||||||||||||
End point description |
Clinically meaningful platelet response was defined as platelet count of ≥50×10^9/L. Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Day 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants with Response defined as platelet count ≥30*10^9/L and at least doubling of baseline, at least 2 separate occasions at two adjacent nominal visits at least 7 days apart, and absence of bleeding | ||||||||||||
End point description |
Response was defined as platelet count ≥30×10^9/L and at least doubling of baseline, at least 2 separate occasions at two adjacent nominal visits at least 7 days apart, and absence of bleeding. Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Baseline during Treatment Period (up to Week 25)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to first rescue therapy | ||||||||||||
End point description |
Time to first rescue therapy was defined as date of first rescue therapy use - date of first treatment + 1. Median was calculated based upon the Kaplan-Meier estimate. Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated. The probability of requiring rescue medication did not reach 0.5 so the KM median in the rozanolixizumab arm could not be estimated. -999 and 999 indicate not available because no formal analysis was carried out as the program was terminated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Baseline to first rescue therapy (up to Week 25)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change from Baseline to Week 25 in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) Symptoms Score | ||||||||||||
End point description |
ITP-PAQ version 1 is a 44 item disease-specific Health-Related Quality of Life questionnaire developed for use in adults with chronic ITP. It includes 10 scales as physical health: Symptoms (6 items), Bother (3 items), Fatigue (4 items), Activity (2 items); emotional health: Fear (5 items) and Psychological (5 items); quality of life (QOL): Work QOL (4 items), Social QOL (4 items), Women’s Reproductive QOL (6 items) and Overall QOL (5 items). Each item is rated on a Likert-type scale containing 4 to 7 responses. All item scores are transformed to a 0 to 100 continuum and are weighted equally to derive individual scale scores and total score (0-100) is calculated as per formula: Sum of item scores within the scale/raw sum range*100. Higher scores indicate better health status. Randomized Set: enrolled study participants who were randomized. Number of Participants analyzed signifies participants evaluable for this endpoint. No formal analysis was carried out as program was terminated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Baseline during Treatment Period (up to Week 25)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With treatment-emergent adverse events (TEAEs) | ||||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose. Safety set included all randomized study participants who received at least one dose of IMP.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Baseline to end of Safety Follow-Up Period (up to Week 31)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With TEAEs leading to withdrawal of investigational medicinal product (ie, study discontinuation) | ||||||||||||
End point description |
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose. Safety set included all randomized study participants who received at least one dose of IMP.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Baseline to end of Safety Follow-Up Period (up to Week 31)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From Baseline to end of Safety Follow-Up Period (up to Week 31)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose. TEAEs were analyzed for Safety Set.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rozanolixizumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received a fixed-unit starting dose of rozanolixizumab sc infusion equivalent to Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of rozanolixizumab sc infusion equivalent to Dose B every 2 weeks until Week 23. After protocol amendment 3, the starting dose was removed and the frequency of administration of the Dose B was changed to weekly. Participants were followed up to a maximum of Week 31. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received a fixed-unit starting dose of placebo sc infusion matched to rozanolixizumab Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of placebo sc infusion matched to rozanolixizumab Dose B every 2 weeks until Week 23. Participants were followed up to a maximum of Week 31. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||
Substantial protocol amendments (globally) |
||||||||||
| Were there any global substantial amendments to the protocol? Yes | ||||||||||
Date |
Amendment |
|||||||||
21 Nov 2019 |
The primary purpose of this substantial amendment (21 Nov 2019) was to incorporate the feedback from the United States Food and Drug Administration (FDA) received on 23 October 2019. In addition to updates to provide clarity and consistency within the protocol and administrative revisions, the following modifications were made:
• Added details on study stopping rules
• Added ADA postdose samples to facilitate clinical validation of drug tolerance in the ADA assay • Eligibility criteria were modified to exclude participants with undiagnosed IgA deficiency and to include patients with moderate renal impairment. • Updated rescue therapy to include any systemic increase in corticosteroids dose above the
Baseline dose • Included new wording specific to the predefined order of formal hypotheses testing and the sequence in which testing would be performed • Added an additional estimand for a secondary endpoint • Provided timing for obtaining IgG samples due to interference of other tests • Country-specific requirements:
− Information specific to Moldova was no longer applicable to the study.
− Updates to Poland were made to align with Polish Health Authority’s and Clinical Trial
Facilitation Group recommendations regarding pregnancy testing.
• Added new wording that local guidelines should be followed regarding antibiotic prophylaxis in asplenic participants to remind investigators about the importance of antibiotic therapy in management of infections in splenectomized participants. |
|||||||||
29 Sep 2020 |
The primary reason for this substantial amendment (29 Sep 2020) was to incorporate changes in the endpoints and the statistical analysis section, and to incorporate agency-required local protocol amendments into 1 global protocol. The country-specific changes were incorporated in Protocol Amendment 2 Appendix. In addition to updates to provide clarity and consistency within the protocol and administrative revisions, the following modifications were made: • Changed the number of additional participants that could be recruited into the study from 75 to 60 (maximum total sample size was changed from 105 to 90) based on revised sample size calculation method and assumptions • Primary analysis (previously incorporated by local Protocol Amendments 1.1, 1.2, and 1.3) − Removed all reference to the Fisher’s Exact test and included as a separate supplemental estimand − Added more details regarding the Cochran-Mantel-Haenszel test • Added details to explain that the interim analysis was to have been conducted on combined data from TP0003 and TP0006, including amendment of the futility stopping rule • Modified study criteria to include study participants who had failed or were intolerant to 2 or more prior ITP therapies per global implementation of an ANSM request and implement feedback received from the FD • Deleted or moved to “other efficacy endpoints” endpoints that did not measure different manifestation of the disease and provided redundant information • Included additional “other” efficacy endpoints • Provided additional wording for clarification on the action taken for study participants on the lowest dose level with a platelet count between >200x109/L and <400x109/L (previously incorporated by local Protocol Amendments 1.2 and 1.3). |
|||||||||
29 Sep 2020 |
This includes the continued information from Protocol Amendment 2 • Added that an independent Quantitative Clinical Pharmacologist/Modeling and Simulation Scientist may have access to the randomization code to review unblinded PK, platelet and serum IgG data to allow modelling activities to be started by an independent scientist • Explained that contingency measures during a pandemic and other exceptional circumstances had been included • Increased the number of sites from 50 to 70 • Country-specific requirements: − United States and Canada only: Updated and clarified study stopping rule per FDA request to change the study stopping rule − Japan only (previously incorporated by local Protocol Amendment 1.2): ▪ Added instructions for SAE reporting (investigational device) and device deficiency reporting specific for Japan, in accordance with local regulations in Japan ▪ Added chest X-ray assessment to early withdrawal (EW) visit and EOS visit to confirm safety at study termination ▪ Added the T-SPOT test as a recommended IGRA test in addition to the QuantiFERON test ▪ Included details on the consent requirements for participants aged <20 years of age ▪ Added exclusion criterion relative to partial splenic artery embolization as this procedure might have been used for treatment of ITP in Japan ▪ Removed wording on use of cannabinoids and medicinal marijuana because these drugs are prohibited by law in Japan. |
|||||||||
03 Dec 2021 |
The primary reason for this substantial amendment (03 Dec 2021) was to modify the dosing regimen of the study on the recommendation of the IDMC. Only 1 study participant was enrolled under Protocol Amendment 3, and this participant was not treated prior to study termination. Thus, this aCSR, including analysis of the data for this study, was based on the protocol under Amendment 2. |
|||||||||
Interruptions (globally) |
||||||||||
| Were there any global interruptions to the trial? Yes | ||||||||||
|
||||||||||
Limitations and caveats |
||||||||||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | ||||||||||
| None reported | ||||||||||
