Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04754542 |
| Other study ID # |
20-2772 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 18, 2021 |
| Est. completion date |
November 30, 2022 |
Study information
| Verified date |
December 2022 |
| Source |
University of Colorado, Denver |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The Main Hypothesis of this extension trial is that among those who have successfully
discontinued their DMT as part of the DISCOMS trial (i.e. did not have a new MS relapse or
brain MRI lesion) and remain off DMT after DISCOMS are at no greater risk of new or worsened
MS disease activity compared to those who successfully continued their DMT as part of DISCOMS
and remain on DMT, each assessed at least one year after termination of the primary DISCOMS
study.
Description:
This will be a non-randomized, rater-blinded pragmatic trial, which is an extension of the
randomized discontinuation trial (RDT), DISCOMS. While RDTs have been done in cancer, and
rheumatoid arthritis patients, the original DISCOMS protocol was the first such study in MS.
Study sites will be limited to the top 10 recruiting sites from the DISCOMS study due to
financial and cost-effectiveness issues. Those sites will have participants who have
completed 18-24 months of the primary study. In practice, the vast majority, if not all, will
have completed 24 months. The investigators will explicitly include any who have completed,
including those who already have exceeded 12 additional months after completion of the
primary trial. Individuals who have successfully completed (retained original drug assignment
and did not meet the primary endpoint of DISCOMS) the primary DISCOMS trial and are willing
to retain their original drug assignment after completion and for an additional 12 months
will be offered entry into the extension. The only exception to that will be individuals who
continued the original drug assignment during and after the primary trial, up to 24 months,
but who then had a relapse, new MRI lesion, or other MS-related reason between months 24 and
36 which resulted in their change of medication assignment. These individuals can and should
be included, and counted as "failing" during the extension trial completing the Kaplan-Meier
event free survival curve critical to the original hypothesis. A total of up to 100 patients
will be consented and enter the extension trial, regardless of assignment, on a first come
first serve basis to avoid selection biases to the extent possible. The intent is to take the
first 100 who fulfill criteria and agree to participate. The plan is for a 50/50
distribution, but there may not be exactly 50 in each group. As of September 1, 2020, 102 had
completed participation of the primary 24-month study, and information as to DMT use after
finishing 2-years participation in DISCOMS was available for 46/102, 23 in each group (see
Table 1 below). Notably, in the Discontinue group, 87% remained off DMT while only 61% in the
Continue group remained on a DMT (13/14 on the same DMT, one switching to an alternative).
Overall 74% remained in the primary assignment grouping. If these ratios stay consistent as
more finish DISCOMS, discontinuers will account for roughly 59% of the total enrolled in the
extension trial. Also, of the 102 completers, 20 have also gone at least an additional 12
months since completion of DISCOMS, and these participants will be offered entry into the
extension trial, should these participants otherwise fulfill criteria. There will be no
placebo and no sham treatment.
The study procedures will be slightly different for those who are completing Month 24 of the
primary trial and simply "rolling over" to extension on the same day, compared to those who
already have completed the study. For those rolling over at Month 24, DISCOMS participants
will be offered participation in the extension trial. If these participants agree to
participate, these participants will do a second study visit at the Month 24 visit, which
concurrently will be Time Zero (T0) for the extension. This will consist of obtaining
informed consent and going through Inclusion/Exclusion criteria. All the data from Month 24
visit will comprise the baseline data for the extension. Current and past DISCOMS study
participants will be identified and screened for eligibility. This may include individuals
who already have surpassed a full year since last participation in the trial, so long as
these participants continued their original group assignment after the completion of the
primary study and for at least for one additional year, or until a relapse or new MRI lesion
occurred, as determined in screening. These individuals will explicitly be included, upon
verification of the defining event. Patients will be approached at their next study visit or
by phone (if these participants already completed the original study) by the PI and/or a
study coordinator about participating in the study. The local PI for the study will verify
accuracy of meeting inclusion criteria, and screening and consent may take place in person or
by electronic means. Participants must agree to have a single SOC, month 36 MRI done by their
primary neurologist and have the results and the MRI disk sent to the study site, to be
assessed by a blinded central reader as has been done during the primary trial. All research
visits will be conducted at the same time as SOC visits when possible, or as separate visits
if not possible or the patient receives SOC elsewhere. For those who have exceeded 30 months
from onset in the primary trial, the P1 visit (a telephone call) will not occur. All patients
will undergo the T1 visit at 36 months, or longer should these participants have already
exceed 36 months from onset of their participation in the primary trial.
A thorough discussion of the trial, signing the informed consent form, and confirmation of
inclusion/exclusion criteria will be completed during the baseline visit (T0). Consenting may
be done in-person on paper or using e-consent. If utilizing e-consent, participants will be
presented a consent form ahead of time, and upon signature in the REDCap system, participants
will receive a pdf of what was 'signed' electronically via REDCap. A pdf will also be
generated for study records. T0 may occur on the same day as T1 if the patient has already
completed the main DISCOMS study and is within the window for the Month 36 visit. There will
be one phone call (P1), conducted by the study coordinator, at 30 Months post-enrollment in
the original DISCO MS trial. On this phone call, the participant will be asked about any new
or ongoing adverse events, changes to medications, and any symptoms suggesting a potential
relapse. If the participant joins the Extension study after the participant already passed 30
Months post-enrollment in the original DISCO MS trial, the participant will not do P1. Those
who have already exceeded 30 months since starting the primary DISCOMS trial will have the
equivalent of the phone assessment at the T0 visit. Participants will come in for 1
additional study visit: T1 at 36 Months post-enrollment in the original DISCO MS trial.
During T1, patients will undergo a blinded EDSS exam and relapse assessment, vitals, complete
an SDMT assessment, and will complete all PROs/comorbidities. All PROs/comorbidities may be
completed on paper in person or remotely via the electronic platform within the visit window,
based on site and patient needs. Participants will also undergo a standard of care MRI scan
of the brain at T1, within 60 days before and 120 days after the study visit. Participants
who have already exceeded 12 months from the end of the primary trial will still be recruited
and simply do the T1 visit at their earliest convenience. The maximum window will be 30
months after completion of the primary study, or 54 months since starting DISCOMS.
Participants should always be brought in as close to 36 months as possible. Some
participants' final study visit for the original DISCO MS study will be at 18 Months. For
these subjects, the P1 visit will occur 24 Months after enrollment in the original study, and
T1 will occur 30 Months after enrollment in the original study.
All participants will undergo the T1 visit, which will include a formal, blinded relapse
assessment by the Examining Physician (EDSS rater) in conjunction with the PI (see section
E). Prior to enrollment, the enrolling physician will certify, based on their personal review
of the prior MRI scans and/or reports which will include data from the 24 month primary
DISCOMS trial, that the scans have been stable for a minimum of 4.5 years (review of minimum
of two scans, although it could be more, separated by at least 4.5 years). MRI scans at T1,
36+ months after onset of participation in the primary trial, will be performed as per usual
SOC, paid for by patient insurance, at whatever site is normally used by the patient
(preferably the same scanner each time, and preferably the same scanner as the investigation
site), and should be done on a MRI machine with magnet 1.5 Tesla or greater, with and without
contrast. Gadolinium may be withheld at the discretion of the PI or request of the patient.
The window for T1 MRIs will be 60 day before or 120 days after the T1 study visit, and will
be analyzed by a central, board-certified, blinded neuro-radiologist for new activity
compared to prior scans. All MRI scans will be read locally for safety and clinical purposes,
and PIs will communicate any significant MS or non-MS findings to the primary neurologist
(should the investigator not be the primary neurologist). Any new lesion documented on the T1
MRI scan will prompt delivery of a notice within 48 hours, to the PI, that the patient has
achieved the endpoint of the study, with a description of relevant findings.
In the event of a suspected relapse, the patient will be instructed to contact their
physician and the study coordinator at their local site within 48 hours of new symptoms and
come in for an unscheduled visit and relapse evaluation within seven days of symptom onset.
Use of corticosteroids will be at the discretion of the patient and the local PI or other
physician. Use of systemic steroids to treat MS symptoms will be concluded to be a
Protocol-defined relapse. As at scheduled visits, the determination of a relapse at an
unscheduled visit will be made by the blinded EDSS examiner, who will perform the EDSS and
only then receive information about recent clinical history.
