Primary objective:- To assess the clinical efficacy of efgartigimod IV 10mg/kg administered in a q2w continuous regimen compared to that administered in a cyclic regimen.Secondary objectives:- To evaluate the safety and tolerability of both…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Mean of the average Myasthenia Gravis Activities of Daily Living (MG-ADL) total
score change from baseline during the visit of week (W)1 through W21 by regimen
arm.
Secondary outcome
Secondary endpoint:
1: Incidence and severity of adverse events (AEs), serious adverse events
(SAEs) and AEs of special interest (AESIs) Time point: 126 weeks
2: Incidence of serious adverse events (SAEs) and AEs of special interest
(AESIs) Time point: 126 weeks
3: Change from baseline in the Myasthenia Gravis - Activities of Daily Living
(MG-ADL) total score over time. A higher total score indicates
more impairment. Time point: 128 weeks
4: Normalized area under the effect curve (AUEC) of MG-ADL total score
improvement from baseline during following intervals: Day 1 through
Week7, Week 7 through Week 14, Week 14 trough Week 21 and Week 7 through Week
21. Time point: 21 weeks
5: Characterization of MG-ADL total score change from baseline during the
following 5 intervals using mean and standard deviation: Week 1
through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through
Week 21 and Week 1 through Week 21. Time point: 21
weeks
6: Number of participants who have a >=2, 3, 4, or 5 points improvement in
MG-ADL total score from baseline. during the following 5 intervals:
Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8
through Week 21 and Week 1 through Week 21. Time
point: 21 weeks
7: percentage of participants who have a >=2, 3, 4, or 5 points improvement in
MG-ADL total score from baseline during the following 5
intervals: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week
21, Week 8 through Week 21 and Week 1 through Week
21. Time point: 21 weeks
8: Percentage of time, participants have a change in MG-ADL total score of at
least 2 points from baseline during Week 4 through Week 21. Time
point: 21 weeks
9: Number of participants who achieve minimal symptom expression (MSE), defined
as a MG-ADL total score of 0 or 1. Time point: 21 weeks
10: Percentage of participants who achieve minimal symptom expression (MSE),
defined as a MG-ADL total score of 0 or 1 in the following 5
intervals: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week
21, Week 8 through Week 21 and Week 1 through Week
21. Time point: 21 weeks
Background summary
Generalized myasthenia gravis (gMG) is a disorder where your immune system
attacks your muscles. This leads to muscle weakness in different places in your
body. It is caused by an error in the transmission of nerve impulses to
muscles. It occurs when normal communication between the nerve and muscle is
interrupted. The treatment of gMG is based on a variety of medications and
medical procedures used either alone or in combination. Since the majority of
already existing treatment options can give side-effects in patients while not
always giving the symptom control needed there is room for improvement. The
study drug wants to be an alternative or addition to the existing therapies
offering more specific modulation of the immune system with less side-effects.
The study drug is a fragment of a human antibody that has been modified to
better bind to a specific protein, called FcRn. Antibodies are proteins that
our body uses to fight and prevent infections. In some diseases, antibodies can
attack your own body. The FcRn protein keeps the antibody level up. The study
drug is a compound that is similar to these antibodies that are naturally
present in the human body. The levels of antibodies are reduced after the study
drug binds to FcRn. This means that the levels of antibodies attacking your own
body are also reduced.
Study objective
Primary objective:
- To assess the clinical efficacy of efgartigimod IV 10mg/kg administered in a
q2w continuous regimen compared to that administered in a cyclic regimen.
Secondary objectives:
- To evaluate the safety and tolerability of both treatment regimens used
throughout the study.
- To assess the clinical efficacy of efgartigimod IV in both treatment regimens
over time.
- To compare the number of participants who achieve maximal clinical effect
during different treatment regimens.
Study design
This is a phase 3b, multicenter, randomized, open-label, parallel-group study
to evaluate alternative dosing regimens for the IMP in patients with gMG. The
clinical efficacy, maximum clinical effect, safety, and tolerability will be
assessed for 2 treatment regimens: cyclic and continuous.
The target population in adult patients with gMG who have an MG-ADL total scole
of more than 5 points and more than 50% of the total score attributed to
nonocular symptoms at screening and baseline.
All participants will be confirmed to be seropositive for AChR-Abs.
Participants must be receiving concomitant gMG treatment from screening through
the end of Part A.
All participants will start Part A by receiving the cyclic regimen, receiving
efgartigimod infusions q7d during a 3-week induction period for a total of 4
infusions.
After the fourth infusion at W3, the 2 regimens will be compared in a regimen
comparison period. On the day 1 visit, participants will be randomized 3:1 to
either the continuous or cyclic regimen. Part A ends after all predose
assessments are performed at the W21 visit.
The cyclic regimen comprises IMP administered q7d in 3-week TPs for 4
infusions, separated by 4-week IPs. The continuous regimen comprises infusions
q2w.
Part B begins with the infusion at the W21 visit, with the assessments at this
visit acting as the baseline for Part B. Participants in the cyclic regimen arm
will receive 1 additional TP of 4 weekly infusions during W21 through W24 as
bridging doses before switching to a continuous regimen at AV26. Participants
in the continuous regimen arm will continue with the continuous regimen in Part
B.
If efgartigimod becomes commercially available for patients with gMG or
available through another patient program for gMG, participants will have the
choice to switch to one of these options after completing Part A of the study.
After W21 for participants in the continuous regimen arm or during W28 for
participants in the cyclic regimen arm, participants who have maintained
clinical improvement, based on clinical judgment and guided by the MG-ADL
scale, will have the option to transition to receiving the IMP q3w. All other
participants will continue to receive IMP infusions q2w.
Participants who are unable to maintain clinical improvement based on clinical
judgment after transitioning to the q3w infusion regimen will return to the q2w
infusion regimen. The decision to switch between the q2w and q3w dosing
regimens must be made on the last dosing day of the current dosing regimen (ie,
at least 2 weeks before the next dose).
Participants who resume the q2w regimen and maintain clinical improvement for 1
year while receiving the q2w regimen will have another opportunity to
transition to the q3w regimen.
The total study duration is up to 128 weeks. The study consists of:
* Approximately 2 weeks of screening, with an additional 7 days allowed as
needed to ensure all lab tests results have been received
* Part A (regimen comparison period) - 21 weeks
* Part B (extension period) - up to 105 weeks
Intervention
The study duration is a maximum of 128 weeks, comprising the following study
periods:
• Screening period - approximately 2 weeks, with an optional additional 7 days
allowed to ensure all test results have been received
• Part A (regimen comparison period) - 21 weeks
• Part B (extension period) - up to 105 weeks
Participants will receive efgartigimod throughout the study. Starting after the
W3 visit through the W21 visit, participants will be on either a cyclic regimen
or a continuous regimen based on the randomization performed on day 1. In Part
B, all participants will transition to a continuous regimen.
Part A
All participants will receive 4 weekly IMP infusions at day 1 (W0), W1, W2, and
W3. Participants randomized to the cyclic regimen arm will receive an
additional 2 cycles of efgartigimod (each including TP infusions q7d for a
total of 4 infusions in 3 weeks followed by a fixed 4-weeks IP), starting at
W7. Participants randomized to the continuous regimen arm will receive
efgartigimod q2w, starting at W5. Part A ends after all predose assessments
have been performed at the W21 visit.
Part B
Part B begins with the infusion at the W21 visit. The assessments taken at W21
will also serve as the baseline assessments for Part B. Participants in the
cyclic regimen arm will receive 1 additional TP of 4 weekly infusions during
W21 through week 24 as bridging doses before switching to a continuous regimen
during week 26. Participants in the continuous regimen arm will continue with
the continuous regimen in Part B.
Study burden and risks
The participant's participation in this study will last up to 128 weeks and
consists of:
* Approximately 2 weeks of screening, with an additional 7 days allowed as
needed to ensure all lab tests results have been received
* Part A (regimen comparison period) - 21 weeks
* Part B (extension period) - up to 105 weeks
The participant will visit the hospital approximately 65 times during this
period. Each visit will take among 4 hours to complete.
The study will consist of a screening, treatment and a follow-up period.
The following tests and procedures will take place during the hospital visits:
• Physical exam (including body weight and hight), vital signs.
• ECG
• Blood and urine samples
• Pregnancy tests in women of childbearing potential
• Covid-19 test using a swab
• Questionnaires
• Ask about their ethnicity
Please refer to page 20-26 of the protocol (schedule of events) for more
information.
Possible side effects that are already known are described in the
Investigator's Brochure and in paragraph 6 of the subject informed consent
form.
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Listed location countries
Age
Inclusion criteria
Participants are eligible to be included in the study only if all of the
following criteria apply:
1. Capable of giving signed informed consent as described in Section 10.1.3 of
the protocol, which includes compliance with the requirements and restrictions
listed in the informed consent form (ICF) and in this protocol.
2. At least 18 years of age, at the time of signing the informed consent.
3. Diagnosed with gMG with confirmed documentation and supported by a physical
exam and confirmed seropositivity for AChR-Abs by the central laboratory.
During the screening or rescreening period, any historical results for AChR-Ab
can be used, as long as the results are <=1 year old.
4. Meets the clinical criteria as defined by the Myasthenia Gravis Foundation
of America (MFGA) class II, III, or IV
5. Has an MG-ADL total score >=5 at screening and the day 1 visit, with more
than 50% of the score due to nonocular symptoms.
6. Concomitant gMG treatment is permitted. Permitted concomitant gMG treatment
includes nonsteroidal immunosuppressive drugs (NSIDs), steroids, and/or (AChE)
inhibitors. If receiving corticosteroids and/or NSIDs, must be on a stable dose
for at least 1 month before screening.
7. Agrees to use contraceptive measures consistent with local regulations and
the following:
a. Male participants: (contraceptive measures provided in Section 10.4.2.2 of
the protocol, refer to Section 10.7 of the protocol for country specific
requirements)
b. WOCBP (defined in Section 10.4.1 of the protocol) must have a negative serum
pregnancy test at screening and a negative urine pregnancy test at baseline
before receiving IMP (Section 10.4.2.1. of the protocol, see Section 10.7 of
the protocol for country-specific requirements).
Exclusion criteria
Participants are excluded from the study if any of the following criteria
apply:
1. Clinically significant uncontrolled active or chronic bacterial, viral, or
fungal infection at screening that is not sufficiently resolved in the
investigator's opinion.
2. A positive test for SARS-CoV-2 at screening
3. Any other known autoimmune disease that, in the opinion of the investigator,
would interfere with an accurate assessment of the clinical symptoms of gMG
and/or put the participant at undue risk.
4. History of malignancy unless deemed cured by adequate treatment with no
evidence of reoccurrence for >=3 years before the first administration of the
IMP. Participants with the following cancers can be included at any time,
provided they are adequately treated at screening: a. Basal cell or squamous
cell skin cancer b. Carcinoma in situ of the cervix c. Carcinoma in situ of the
breast d. Incidental histological finding of prostate cancer (TNM stage T1a or
T1b)
5. Clinical evidence of other significant serious diseases, a recent (<3
months) major surgery, or any other condition that, in the opinion of the
investigator, could confound the results of the study or put the participant at
undue risk
Design
Recruitment
Medical products/devices used
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 | EUCTR2021-002504-12-NL |
| ClinicalTrials.gov | NCT04980495 |
| CCMO | NL79087.018.22 |