Clinical Trial Results:
An Open-Label Safety Extension Study (OLSES) Evaluating the Long term Safety and Durability of Response of CHS 0214 (CHS 0214-05)
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Summary
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EudraCT number |
2015-000665-30 |
Trial protocol |
GB ES DE IT |
Global end of trial date |
18 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Oct 2018
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First version publication date |
26 Oct 2018
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Other versions |
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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 |
CHS-0214-05
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Coherus BioSciences, Inc.
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Sponsor organisation address |
333 Twin Dolphin Drive, Suite 600, Redwood City, United States, CA 94065
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Public contact |
Barbara K. Finck, MD
Chief Medical Officer, Coherus BioSciences, Inc., 001 650-649-3530, bfinck@coherus.com
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Scientific contact |
Barbara K. Finck, MD
Chief Medical Officer, Coherus BioSciences, Inc., 001 650-649-3530, bfinck@coherus.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 |
03 Jan 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Apr 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Oct 2017
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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 |
The purpose of this open-label safety extension study (OLSES) was to evaluate the longer-term safety and durability of response of subjects who completed 48 weeks of evaluations in the confirmatory safety and efficacy studies, CHS 0214-02 or CHS 0214-04, evaluating CHS 0214 in rheumatoid arthritis (RA) and plaque psoriasis (PsO), respectively.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki and with all applicable local and country laws and regulations where the study was conducted, and in compliance with the International Council for Harmonisation E6 Good Clinical Practice Guidelines.
The rationale of the study, procedural details, and investigational goals were explained to each subject, along with potential risks and benefits. Each subject was assured of his/her right to withdraw from the study at any time. Prior to the initiation of any study procedures, each subject signed and dated an approved informed consent form (ICF). Informed consent was obtained from subjects again if the ICF was revised during their study participation.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
08 Jul 2015
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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 |
Spain: 2
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 22
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Australia: 16
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Country: Number of subjects enrolled |
Canada: 50
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Country: Number of subjects enrolled |
Israel: 15
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Country: Number of subjects enrolled |
Japan: 164
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Country: Number of subjects enrolled |
South Africa: 86
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Worldwide total number of subjects |
359
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EEA total number of subjects |
28
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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) |
319
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From 65 to 84 years |
40
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85 years and over |
0
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Recruitment
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Recruitment details |
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Pre-assignment
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Screening details |
Within 1 month of their Week 48 Visit of the parent study (either CHS-0214-02 or CHS-0214-04). | ||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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RA Population | ||||||||||||||||||||||||||||||||||||
Arm description |
The RA Population included all subjects with RA who completed Study CHS-0214-02, met the entry criteria for enrollment into Study CHS-0214-05, received at least 1 dose of CHS-0214, and had any efficacy measurements. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHS-0214
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received open-label study drug (CHS-0214) 50 mg every week in prefilled syringes with passive needle guard by self-injection or by a caregiver at home as a subcutaneous injection.
Subjects received study drug for 48 weeks except in Japan, where subjects were allowed to receive study drug until marketing approval. Subsequently, the study was terminated prior to any application for marketing approval.
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Arm title
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PsO Population | ||||||||||||||||||||||||||||||||||||
Arm description |
The PsO Population included all subjects with PsO who completed Study CHS-0214-04, met the entry criteria for enrollment into Study CHS-0214 05, received at least 1 dose of CHS-0214, and had any efficacy measurements. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHS-0214
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received open-label study drug (CHS-0214) 50 mg every week in prefilled syringes with passive needle guard by self-injection or by a caregiver at home as a subcutaneous injection.
Subjects received study drug for 48 weeks.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 359 subjects were enrolled in the trial, but only 356 subjects were included in the Full Analysis Population (FAP), this included all subjects who received 1 or more doses of study drug and had any efficacy measurements. From Parent Study CHS-0214-04 (PsO), 2 subjects did not receive at least 1 dose of study drug and 1 subject from Parent Study CHS-0214-02 (RA) did not have any efficacy measurements. As these 3 subjects did not meet the FAP criteria they were not reported in the baseline period. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
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Subject analysis sets
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Subject analysis set title |
Japanese RA Population
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
The Japanese RA Population included all subjects with RA who completed Study CHS-0214-02 at Japanese sites, met the entry criteria for enrollment into Study CHS-0214-05, received at least 1 dose of CHS-0214, and had any efficacy measurements.
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End points reporting groups
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Reporting group title |
RA Population
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Reporting group description |
The RA Population included all subjects with RA who completed Study CHS-0214-02, met the entry criteria for enrollment into Study CHS-0214-05, received at least 1 dose of CHS-0214, and had any efficacy measurements. | ||
Reporting group title |
PsO Population
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Reporting group description |
The PsO Population included all subjects with PsO who completed Study CHS-0214-04, met the entry criteria for enrollment into Study CHS-0214 05, received at least 1 dose of CHS-0214, and had any efficacy measurements. | ||
Subject analysis set title |
Japanese RA Population
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Japanese RA Population included all subjects with RA who completed Study CHS-0214-02 at Japanese sites, met the entry criteria for enrollment into Study CHS-0214-05, received at least 1 dose of CHS-0214, and had any efficacy measurements.
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End point title |
Durability of response (maintenance of an ACR20 response or greater) [1] [2] | ||||||||||||
End point description |
In subjects with RA, the primary efficacy endpoint was the durability of response (maintenance of an ACR20 response or greater), which was measured at each visit. The ACR20 is a composite endpoint
based on the following assessments:
· 66/68 swollen joint count (SJC) or tender joint count (TJC),
· Subject’s pain assessment (SPA)-visual analog scale (VAS),
· Subject’s global assessment of disease activity (SGA)-VAS,
· Physician’s global assessment of disease activity (PGA)-VAS,
· Health Assessment Questionnaire-Disability Index (HAQ-DI), and
· High sensitivity C-reactive protein (hs-CRP).
The baseline value to assess the ACR20 during this study was the same baseline value used to assess the ACR20 during the parent study (ie, the Week 0 assessment in the parent study).
ACR20 = 20% improvement according to American College of Rheumatology criteria.
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End point type |
Primary
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End point timeframe |
For 48 weeks from the start of treatment. In the Japanese population, subjects were allowed to receive study drug until marketing approval. Subsequently, the study was terminated prior to any application for marketing approval.
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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: In this study, the changes in ACR score over time were compared to the baseline values measured at Week 0 of the parent study (CHS-0214-02) in order to measure the maintenance over time of a response already obtained in the parent study. Hence, the baseline values used to calculate the maintenance of this response were the same between Studies CHS‑0214-02 and CHS-0214-05 (OLSES) for subjects with RA. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary efficacy endpoint of durability of response is defined differently for subjects with RA and subjects with PsO, which explains why not all the baseline period arms are reported on. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Durability of response (maintenance of PASI-50 response or greater) [3] [4] | ||||||||
End point description |
For subjects with PsO, the primary efficacy endpoint was the durability of response (maintenance of PASI-50 response or greater), which was measured at each visit.
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End point type |
Primary
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End point timeframe |
For 48 weeks from the start of treatment.
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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: In this study, the changes in PASI scores over time were compared to the baseline values measured at Week 0 of the parent study (CHS-0214-04) in order to measure the maintenance over time of a response already obtained in the parent study. Hence, the baseline values used to calculate the maintenance of this response were the same between Studies CHS‑0214‑04 and CHS‑0214-05 (OLSES) for subjects with PsO. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary efficacy endpoint of durability of response is defined differently for subjects with RA and subjects with PsO, which explains why not all the baseline period arms are reported on. |
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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 |
Adverse events were collected from Week 0 Day 0 Visit through the Follow-up Visit 28 days after last dose of study drug. Ongoing adverse event from the subject’s involvement in Studies CHS-0214-02 or CHS-0214-04 was continued as TEAEs in OLSES.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
RA & PsO Population
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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13 Jul 2015 |
-Revised Early Termination Visit to Follow-up Visit 28 days after the last dose of study drug
-Diaries to be electronic
-For eligible subjects to the OLSES:
.Data collected Week 48 Visit of parent study will consider Week 0 Day 0 data in the OLSES
.If eligibility isn't determined and consent isn't obtained Week 48 Visit of parent study, subjects will come back within 1 month of Week 48 Visit to complete procedures/testing required for OLSES Subject to be given study drug supply
-Subjects removed from therapy or assessment if positive viral screen results (Week 48 laboratory results referred to CHS-0214-02 or CHS-0214-04)
-Removed not meeting enrollment goals as reason Sponsor’s temporary suspension or premature termination of the study
-Added text recommended Enbrel dose subjects with RA and PsO
-If injection is planned on the day of a study visit, should be performed after the completion all visit procedures, blood sample collected represents trough serum sample
-Concomitant medications changes NSAID, prednisone, and MTX doses
-Glucocorticoids prohibited concomitant medications subject could be on a stable dose of drugs that may cause new onset or exacerbation of psoriasis
-Check dosing per protocol and provision of retraining
-Added guidelines for the management hepatitis B infection
-SGA-VAS performed after PGA-VAS for RA and after PSGA for PsO at Weeks 4, 24, 48, and 52
-Medical and surgical history will not be collected but referenced from the parent study
-PASI score assessors demonstrate proficiency performing PASI attempts to use same assessor
-Added secondary efficacy endpoints for the RA Population
-Ongoing AEs from CHS-0214-02 or CHS 0214-04 should continue
-RA durability of response definition and correct baseline values
-PsO durability of response definition and correct baseline values
-Sponsor written permission for publication and study-related info
-Removed pregnancy test language for subjects in Argentina |
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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. | |||
| None reported | |||
