The primary objective of this study is to assess the long-term efficacy of COMP360 with respect to use of new antidepressant treatment, hospitalisations for depression, suicidality, and depressive severity rated using the Montgomery and Asberg…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this long-term follow up study will be time to the
first of any of the following depression-related events (from baseline ie one
day prior to single dose COMP360 administration dosing in the prior study) in
participants recruited from the COMP 001 study (presented for the 1 mg , 10 mg,
and 25 mg COMP360 therapy groups):
• Initiation of new antidepressant treatment (first new antidepressant
treatment in time period only)
• Hospitalization due to depression
• Suicide attempt, prevention of an imminent suicide attempt, or completed
suicide
• Increased suicidality measured by worsening on MADRS item 10 i.e. either 1) a
score of 5 or 6 on MADRS item 10; or 2) an increase of 2 points compared to
Baseline in the prior study MADRS 10 score provided the score is >=3.
• Worsening in the MADRS clinician rated severity scale: i.e. a 5 point
worsening compared to baseline score in the prior study at any timepoint
post-baseline of the original study; or a worsening of >=5 points (providing the
highest score is >=15) across two or more consecutive visits (in this case the
first date of the >=5 point increase will be classed as the event and at the
final study visit the >=5 point worsening will qualify as an event without need
for confirmation at a subsequent visit)
Secondary outcome
The secondary endpoints are:
• Change in MADRS total score from Baseline of the prior study to 12 , 16, 20,
24, 28. 40, and 52 weeks post COMP360
• The proportion of participants with a response (defined as a >= 50%
improvement in MADRS total score from Baseline of the prior study) at Week 12 ,
16, 20, 24, 28, 40, and 52 post COMP360
• The proportion of participants with remission (defined as a MADRS total score
<= 10) at Week 12, 16, 20, 24, 28, 40, and 52 post COMP360
• The proportion of participants who have a sustained response at Week 12, 16,
20, 24, 28, 40 and 52. Sustained response is defined as the proportion of
patients fulfilling response criteria at any visit up to and including Week 3
post-dosing (in the lead-in studies), that also fulfills response criteria at
all subsequent visits up to and including Week 12, 16, 20, 24, 28, 40, and 52
post COMP360. Response is defined as >= 50% decrease in MADRS total score from
Baseline of the prior study
• Longitudinal depression severity: the difference in the area under the curve
between 1mg, 10 mg, and 25 mg COMP360 monotherapy and 25 mg COMP360 adjunctive
therapy over 52 weeks post-baseline in QIDS-SR-16 total score
• Work and Social Adjustment (WSAS) score change from Baseline of the prior
study to week 12, 18, 24, 30, 36, 42, 48
• Sheehan Disability Scale (SDS) score change from Baseline of the prior study
to week 12, 16, 20, 24, 28, 40, and 52 post COMP360
Background summary
A recent open label study of the effects of COMP360 in participants with
treatment resistant depression (TRD) showed rapid, significant decrease of
depressive symptoms after treatment with COMP360 coupled with psychological
support. Over 40% of participants sustained response at 3 months. Given
promising indications of efficacy, a phase IIb trial aiming to recruit 216
participants with TRD is currently underway: *The safety of COMP360 in
participants with treatment-resistant depression* (P-TRD) study, also referred
to as COMP 001. The aim of COMP 001 is to evaluate the efficacy and safety of
COMP360 (25 mg or 10 mg) compared to 1 mg COMP360, administered under
supportive conditions to adult participants with TRD over 12 weeks. In
addition, there is an ongoing phase II, open-label study exploring the safety
and efficacy of 25 mg COMP360 as an adjunctive therapy to ongoing selective
serotonin reuptake inhibitors (SSRIs) in participants with TRD (referred to as
COMP 003).
In this present study (COMP 004), the aim is to follow up participants from
COMP 001 and COMP 003 in a long-term follow up study, with both remote and
digital assessments, to explore the long term efficacy and safety of the three
different doses of COMP360 (1 mg, 10 mg, and 25 mg) administered to patients
with TRD as a monotherapy in COMP 001 and 25 mg COMP360 administered as an
adjunct to an SSRI in COMP 003. Patients previously treated in COMP001 will be
followed for approximately 40 weeks and patients previously treated in COMP003
will be followed for approximately 49 weeks giving a total follow up period of
52 weeks from COMP360 dosing.
Study objective
The primary objective of this study is to assess the long-term efficacy of
COMP360 with respect to use of new antidepressant treatment, hospitalisations
for depression, suicidality, and depressive severity rated using the Montgomery
and Asberg Depression Rating Scale (MADRS) over a total of 52 weeks (compared
across the 1 mg, 10 mg and 25 mg COMP360 groups from COMP 001).
The secondary objectives are:
• To assess response, sustained response, remission and change in depression
severity (compared across all treatment groups - 1 mg, 10 mg and 25 mg COMP360
in COMP 001 and 25 mg as an adjunct to SSRIs in COMP 003) over a total of 52
weeks
• To evaluate the effect of COMP360 on functioning and associated disability
compared across the groups over a total of 52 weeks
The safety objective is:
• To evaluate the safety of COMP360 in participants with TRD based on adverse
events (AEs) reported over the full follow-up period (a total of 52 weeks)
since COMP360 administration
The exploratory objectives are:
• To evaluate the effects of COMP360n on quality of life, self reported
depression and anxiety, and healthcare utilization and productivity losses
compared across the groups over a total of 52 weeks
• To assess the long-term efficacy of COMP360 with respect to use of new
antidepressant treatment, hospitalizations for depression, suicidality, and
depressive severity rated using the Montgomery and Asberg Depression Rating
Scale (MADRS) over a total of 52 weeks in participants recruited from COMP 003
• To assess the long-term efficacy of COMP360 with respect to use of new
antidepressant treatment, hospitalizations for depression, suicidality, and
depressive severity rated using the self-report Quick Inventory of Depressive
Symptomatology - 16 item over a total of 52 weeks (compared across the 1 mg, 10
mg and 25 mg COMP360 groups from COMP 001) and separately in participants
recruited from COMP 003
• To assess the feasibility of conducting a long-term follow up study in
participants who received COMP360 therapy for TRD
• To evaluate the impact of different COMP360 doses on real life functional
activity estimated from passive data streams collected on a mobile app on
participants* mobile phones
Study design
This is a long-term follow up study of participants who have previously taken
part in the dose ranging phase 2b, international, multicenter, randomized,
fixed dose double blind COMP 001 trial or the open-label COMP 003 trial
delivering 25 mg COMP360 therapy open label as an adjunct to SSRIs in TRD
patients. The study populations for COMP 001 and COMP 003 includes adult men
and women, 18 years of age and older, with TRD. Participants will be enrolled
into this long-term follow up study once they have completed their final study
visit in the COMP 001 or COMP 003 trial, ie this will be a non-probability
sample.
This long-term follow up study will continue to observe participants who took
part in both the COMP 001 and COMP 003 studies up to a total of 52 weeks post
COMP360 administration. All weeks referenced in this protocol relate to the
time from COMP360 administration in the lead in studies. Participants in COMP
001 are followed up for a total of 12 weeks and participants in COMP 003 are
followed up for a total of 3 weeks in these clinical trials and therefore
participants recruited into this study from COMP 003 will participate in this
follow up study for 9 weeks longer than COMP 001 participants should they
consent to take part. Thus patients previously treated in COMP001 will be
followed for 40 weeks and patients previously treated in COMP003 will be
followed for 49 weeks.
Only participants who complete the final study visit of COMP 001 and COMP 003
will be recruited into this study.
After signing the informed consent form (ICF) and when the participant has been
determined as eligible for this study by the investigator, participants will be
given access to an online electronic patient-reported outcome (ePRO) system to
complete self-report questionnaires. Automatic reminders for questionnaire
completion will be sent to participants and the study team will demonstrate the
system to participants in this first screening visit.
Participants will complete self-report assessments every 2 weeks (with a visit
window of ± 3 days). As participants recruited from COMP 003 will be recruited
into COMP 004 three weeks after baseline in the previous study (COMP003)
compared with COMP 001 participants who will be recruited 12 weeks after
Baseline, participants from COMP 003 will complete the same assessment schedule
as COMP 001 participants up to week 12 using the following measures: the MADRS,
Work and Social Adjustment Scale (WSAS), Generalized Anxiety Disorder - 7 item
scale (GAD-7), EuroQol- 5 Dimension - 3 level scale (EQ-5D-3L), QIDS-SR-16,
Sheehan Disability Scale (SDS) - interviewer administered version, and
reporting of AEs and concomitant medications/therapies.
Therefore, participants from COMP 003 will be asked to complete the QIDS-SR-16
and MADRS (assessed by a blinded rater) at weeks 6, 9, and 12. They will also
be asked questions regarding concomitant medication/therapy received since
their last study visit, and questions regarding AEs experienced since the
participant*s last assessment by a study investigator at these three timepoints
(week 6, 9, and 12). Additionally, they will be asked to complete the WSAS,
GAD-7, SDS and EQ-5D-3L at week 12 after baseline in COMP 003.
From week 14 onwards, participants recruited from both COMP 001 and COMP 003
will be asked to complete two questionnaires every 2 weeks. The QIDS-SR-16 will
be asked every two weeks and an additional three questionnaires will be rotated
ie asked at every third timepoint in a staggered manner ie assessed every six
weeks rather than every two weeks like the QIDS-SR-16. These three
questionnaires are the EQ-5D-3L, GAD-7, and WSAS. The EQ-5D-3L will be asked at
week 14 (post baseline in the original studies), GAD-7 at week 16 (post
baseline in the original studies), and WSAS at week 18 (post baseline in the
original studies), and this order will be repeated up to and including week 52
post baseline in COMP 001/003.
At 12 weeks (±2 weeks) post the baseline in COMP 001 and COMP 003, all COMP 004
participants will be asked to complete a healthcare utilization measure - the
Treatment Inventory Costs in Patients with psychiatric disorders (TiC-P). The
TiC-P measures medical costs and productivity losses (including absenteeism,
presenteeism, and informal care costs). Participants will be asked this
questionnaire every eight weeks throughout the study ie at 12, 20, 28, 36, 44,
and 52 weeks.
Participants recruited from both COMP 001 and COMP 003 will have remote
assessments with study investigators (the option of an in-person visit will be
provided at the investigator*s discretion) at 16, 20, 24, 28, weeks (all ± 1
week), 40 weeks (± 2 weeks) and 52 weeks (± 2 weeks) post COMP360
administration (ie Day 0 in either the COMP 001 or COMP 003 studies).
Assessments will include the MADRS (conducted by a blinded assessor), Sheehan
Disability Scale (SDS) - interviewer administered version, questions regarding
concomitant medication/therapy the participants has received since their last
study visit, and questions regarding AEs experienced since the participant*s
last assessment with a study investigator.
At the end of the present study (52 weeks post-IP administration in COMP 001 or
COMP 003), participants will be asked to complete an study feedback survey
remotely with a few short questions about how they found the methodology and
frequency of assessments in this long-term follow up study.
The main purpose of this study is to explore the long term safety and efficacy
of COMP360 therapy in patients with treatment-resistant depression. This study
will be a study. No treatments are specified in this protocol and
participants will be treated as per standard clinical practice by their
existing clinicians. No medications or therapies will be prohibited in this
study.
Blinding will be maintained from the COMP 001 phase IIb trial for both site
investigators and participants ie they will not be informed of their treatment
allocation prior to or whilst this long-term follow up trial is ongoing. COMP
003 is an open-label trial and therefore site investigators and patients will
not be blind to treatment allocation. For all participants the MADRS will be
conducted by a blinded, independent rater.
Study burden and risks
N/A
3rd Floor, 1 Ashley Road 1
Altrincham, Cheshire, WA14 2DT
NL
3rd Floor, 1 Ashley Road 1
Altrincham, Cheshire, WA14 2DT
NL
Listed location countries
Age
Inclusion criteria
1)Signed ICF
2)Each participant having completed the final study visit of either COMP 001 or
COMP 003
3)Ability to complete all protocol required assessment tools (including having
access to the internet in order to complete the digital assessments) without
any assistance or alteration to the copyrighted assessments, and to comply with
all study visits
Exclusion criteria
1)Subject has any condition, for which in the opinion of the investigator,
participation would not be in the interest of the subject eg participation
could compromise the wellbeing of the participant or prevent, limit, or
confound the protocol-specified assessments
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001348-25-NL |
| CCMO | NL73761.042.20 |