Clinical Trial Results:
A 2-Part, Phase 2, Open-Label Study of the Safety, Tolerability, and Efficacy of Itacitinib Immediate Release in Participants With Primary Myelofibrosis or Secondary Myelofibrosis (Post–Polycythemia Vera Myelofibrosis or Post–Essential Thrombocythemia Myelofibrosis) Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy
Summary
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EudraCT number |
2020-003123-42 |
Trial protocol |
AT FR DE ES BE PL IT |
Global end of trial date |
24 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Sep 2024
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First version publication date |
05 Sep 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
INCB 39110-213/LIMBER-213
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Incyte Corporation
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Sponsor organisation address |
1801 Augustine Cut-Off, Wilmington, United States, DE 19803
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Public contact |
Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
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Scientific contact |
Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Aug 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Aug 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Part 1 was conducted to evaluate the safety and tolerability of itacitinib immediate release (IR) and to select the recommended phase 2 dose (RP2D) for Part 2 of the study. Part 2 was to be conducted to evaluate the efficacy of itacitinib IR at the RP2D with respect to spleen volume reduction at Week 24.
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Protection of trial subjects |
This study was to be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws and country-specific regulations in which the study was being conducted.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
12 Jul 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 2
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Country: Number of subjects enrolled |
Italy: 2
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Worldwide total number of subjects |
4
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
Pre-assignment
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Screening details |
This study was conducted at 3 study centers in the United States and Italy. | ||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Itacitinib 300 mg | ||||||||||||||
Arm description |
Participants received itacitinib immediate release 300 milligrams (mg) twice a day (BID) orally (PO) for at least 24 weeks. Participants could remain on treatment as long as they were receiving clinical benefit and had not met any criteria for treatment discontinuation. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
itacitinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
100 and 300 mg immediate release tablets
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Baseline characteristics reporting groups
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Reporting group title |
Itacitinib 300 mg
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Reporting group description |
Participants received itacitinib immediate release 300 milligrams (mg) twice a day (BID) orally (PO) for at least 24 weeks. Participants could remain on treatment as long as they were receiving clinical benefit and had not met any criteria for treatment discontinuation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Itacitinib 300 mg
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Reporting group description |
Participants received itacitinib immediate release 300 milligrams (mg) twice a day (BID) orally (PO) for at least 24 weeks. Participants could remain on treatment as long as they were receiving clinical benefit and had not met any criteria for treatment discontinuation. |
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End point title |
Part 1: Number of participants with any treatment-emergent adverse event (TEAE) [1] | ||||||
End point description |
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
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End point type |
Primary
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End point timeframe |
up to 724 days
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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: Statistical analysis was not conducted for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Part 1: Number of participants with any Grade 3 or higher TEAE [2] | ||||||
End point description |
A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
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End point type |
Primary
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End point timeframe |
up to 724 days
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Notes [2] - 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: Statistical analysis was not conducted for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Part 2: Splenic response rate (SRR) at Week 24 [3] | ||||||
End point description |
SRR was defined as the percentage of participants who had a reduction in spleen volume (by imaging) of at least 35% when compared with Baseline.
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End point type |
Primary
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End point timeframe |
Baseline; Week 24
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Notes [3] - 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: Analysis was not conducted because Part 2 never opened for enrollment. |
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Notes [4] - Analysis was not conducted because Part 2 never opened for enrollment. |
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No statistical analyses for this end point |
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End point title |
Part 2: Number of participants with any Grade 3 or higher TEAE | ||||||
End point description |
A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
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End point type |
Secondary
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End point timeframe |
up to at least 24 weeks
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Notes [5] - Analysis was not conducted because Part 2 never opened for enrollment. |
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No statistical analyses for this end point |
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End point title |
Part 2: Total symptom score (TSS) response rate at Week 24 | ||||||
End point description |
TSS response was defined as the percentage of participants who achieved at least 50% reduction in TSS over the 28 days immediately before the end of Week 24 compared with the 7 days immediately before the initiation of itacitinib immediate release (aseline).B
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End point type |
Secondary
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End point timeframe |
Baseline; Week 24
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Notes [6] - Analysis was not conducted because Part 2 never opened for enrollment. |
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No statistical analyses for this end point |
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End point title |
Part 2: Mean change (from Day 1 versus Week 12 and Week 24) in the 5 multi-item functional scale scores and the multi-item global health status scale score (EORTC QLQ-C30) | ||||||||
End point description |
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was to be used to assess the improvement in quality of life.
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End point type |
Secondary
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End point timeframe |
Baseline; Weeks 12 and 24
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Notes [7] - Analysis was not conducted because Part 2 never opened for enrollment. |
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No statistical analyses for this end point |
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End point title |
Part 2: Percentage of participants categorized as improved on the Week 24 Patient Global Impression of Change (PGIC) | ||||||
End point description |
The PGIC consists of a single question pertaining to a participant's overall status since the start of the study. The questionnaire gives participants 7 options to describe their overall status including: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse.
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End point type |
Secondary
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End point timeframe |
Baseline; Week 24
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Notes [8] - Analysis was not conducted because Part 2 never opened for enrollment. |
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No statistical analyses for this end point |
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End point title |
Part 2: Number of participants with any TEAE | ||||||
End point description |
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
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End point type |
Secondary
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End point timeframe |
up to at least 24 weeks
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Notes [9] - Analysis was not conducted because Part 2 never opened for enrollment. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
up to 724 days
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Adverse event reporting additional description |
Treatment-emergent adverse events (TEAEs), defined as AEs that were reported for the first time or the worsening of pre-existing events after the first dose of study treatment, were reported for the Safety Evaluable Population.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22
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Reporting groups
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Reporting group title |
Total
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Reporting group description |
Total | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
itacitinib 300 mg
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Reporting group description |
itacitinib 300 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Jan 2022 |
The study sponsor decided not to proceed with the study any further; the primary purpose of this amendment was to update the Schedule of Activities for study participants ongoing as of the date of this decision to simplify and minimize the required assessments. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The sponsor terminated study enrollment following an assessment regarding the expected duration of recruitment for the Phase 2 portion of the study combined with the availability of other study options for this patient population. |