The objectives of the study are:* To evaluate the safety and tolerability of zilucoplan in subjects with IMNM* To evaluate the efficacy of zilucoplan in subjects with IMNM
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Percent change from Baseline to Week 8 in CK levels.
Secondary outcome
* Change from Baseline to Week 8 in Triple Timed Up and Go (3TUG) Test (in
ambulatory subjects only)
* Change from Baseline to Week 8 in Proximal Manual Muscle Testing (MMT)
* Change from Baseline to Week 8 in Physician Global Activity Visual Analogue
Scale (VAS)
* Change from Baseline to Week 8 in Patient Global Activity VAS
* Change from Baseline to Week 8 in Health Assessment Questionnaire (HAQ)
* Change from Baseline to Week 8 in Myositis Disease Activity Assessment Tool
(MDAAT) Score
* Change from Baseline to Week 8 in American College of Rheumatology/European
League Against Rheumatism (ACR/EULAR) Response Criteria
* Change from Baseline to Week 8 in FACIT-Fatigue Scale
Background summary
See introduction in protocol as from page 18.
Study objective
The objectives of the study are:
* To evaluate the safety and tolerability of zilucoplan in subjects with IMNM
* To evaluate the efficacy of zilucoplan in subjects with IMNM
Study design
RA101495-02.202 is a multicenter, randomized, double-blind, placebo-controlled
study to evaluate the safety, tolerability, and efficacy of zilucoplan in
subjects with IMNM who are positive for anti-HMGCR
(3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) or anti-SRP (signal
recognition particle) autoantibodies.
The planned enrollment is approximately 24 subjects. Subjects will be
randomized in a 1:1 ratio to receive daily SC doses of 0.3 mg/kg zilucoplan or
matching placebo. Randomization will be stratified based on antibody status
(anti-HMGCR+ versus anti-SRP+).
The Main Portion of the study includes a Screening Period of up to 4 weeks and
an 8-week Treatment Period. During the Treatment Period, subjects will return
to the clinic at Week 1, Week 2, Week 4, and Week 8 to evaluate safety,
tolerability, and efficacy. Additional assessments will include biomarker
testing, pharmacokinetics, pharmacodynamics, and optional pharmacogenomics.
Safety assessments will include
physical examinations, vital signs, electrocardiogram (ECG), clinical
laboratory tests, adverse event (AE) monitoring, and immunogenicity.
Randomized subjects will receive 0.3 mg/kg zilucoplan or matching placebo
administered SC at the Day 1 visit. Following in-clinic education and training,
all subjects will self-inject daily SC doses of blinded study drug, according
to randomized treatment allocation, for the subsequent 8 weeks. Single use
pre-filled syringes in injection devices will be provided for use during the
study.
All SOC therapy medications for IMNM should be kept at the same doses
throughout the study, including corticosteroids, immunosuppressive drugs, and
IVIG.
To reduce the risk of meningococcal infection (Neisseria meningitidis), all
subjects must be vaccinated against meningococcal infections (with a
quadrivalent vaccine and, where available and in accordance with local SOC,
serogroup B vaccine) within 3 years prior to, or at the time of, initiating
study drug. Subjects who initiate study drug treatment less than 2 weeks after
receiving a meningococcal vaccine must receive treatment with appropriate
prophylactic antibiotics (e.g., ciprofloxacin, erythromycin, penicillin V)
until at least 2 weeks after initial dose of vaccine(s). Booster vaccinations
should be administered in accordance with local SOC.
During the Treatment Period, to mitigate the risk of infection, subjects will
be counseled and reminded of the early signs and symptoms of Neisseria
meningitidis infection. A patient safety card detailing the signs and symptoms
of infection, with instructions to seek immediate medical attention if any such
symptoms occur, will be provided to each subject.
The safety of subjects will be monitored in a blinded manner on an ongoing
basis. If an unblinded data review should become necessary to ensure subject
safety, a Safety Monitoring Committee (SMC) will convene and evaluate study
data as appropriate.
At the conclusion of the Treatment Period of the study, all subjects will have
the option to receive zilucoplan in the Extension Portion of the study provided
they meet the Extension Portion selection criteria. Visits during the first 8
weeks of the Extension Portion will be identical to the Main Portion of the
study for all subjects to ensure appropriate monitoring of subjects
transitioning from placebo to active treatment. The study will remain
double-blinded until after the data from the Main Portion of the study have
been reviewed, locked, and unblinded.
If a subject permanently discontinues study drug treatment prior to the Week 8
visit for any reason, he/she will not be eligible for the Extension Portion.
For subjects who permanently discontinue treatment with study drug, a Safety
Follow-up Visit will be performed at 40 days after the last dose to collect
information on any ongoing AEs or new SAEs since the last study visit.
Duration of Study Participation
Main Portion: The duration of study participation during the Main Portion will
include a Screening Period of up to 4 weeks and an 8-week Treatment Period for
a total of approximately 12 weeks.
Extension Portion: The investigational medicinal product (IMP) will continue to
be provided by the Sponsor until zilucoplan is approved and available in the
territory, or the Sponsor terminates development of zilucoplan for IMNM. In
countries where zilucoplan is not approved or marketed, but in which sponsored
clinical studies have been conducted, subjects may continue to receive
zilucoplan through a compassionate use pathway.
Intervention
NA
Study burden and risks
See questions E4 till E9.
Battelsesteenweg 455D
Mechelen 2800
NL
Battelsesteenweg 455D
Mechelen 2800
NL
Listed location countries
Age
Inclusion criteria
1. Male or female * 18 years and < 75 years.
2. Able to provide informed consent, including signing and dating the informed
consent form (ICF).
3. Clinical diagnosis of IMNM (Immune-Mediated Necrotizing Myopathy).
4. Positive serology for anti-HMGCR or anti-SRP autoantibodies.
5. Clinical evidence of weakness (* grade 4 out of 5) on manual muscle testing
in at least one
proximal limb muscle group.
6. CK (creatine kinase) of >1000 U/L at Screening.
7. No change in corticosteroid dose for at least 30 days prior to Baseline or
anticipated to occur
during the first 8-weeks on study.
8. No changes in immunosuppressive therapy, including dose, for at least 30
days prior to Baseline or anticipated to occur during the first 8-weeks on
study.
9. Female subjects of childbearing potential must have a negative serum
pregnancy test at Screening and a negative urine pregnancy test within 24 hours
prior to the first dose of study drug.
10. Sexually active female subjects of childbearing potential (i.e., women who
are not postmenopausal or who have not had a hysterectomy, bilateral
oophorectomy, or bilateral tubal ligation) and all male subjects (who have not
been surgically sterilized by vasectomy) must agree to use effective
contraception during the study. Postmenopausal women are, for the purposes of
this protocol, defined as women who have gone 12 consecutive months without
menstruation.
Exclusion criteria
1. History of meningococcal disease.
2. Current or recent systemic infection within 2 weeks prior to Screening or
infection requiring
intravenous (IV) antibiotics within 4 weeks prior to Screening.
3. Pregnant, planning to become pregnant, or nursing female subjects.
4. Recent surgery requiring general anesthesia within 2 weeks prior to
Screening or expected to have surgery requiring general anesthesia during the
8-week Treatment Period.
5. Treatment with a complement inhibitor or an experimental drug within 30 days
or 5 half-lives of
the drug (whichever is longer) prior to Baseline.
6. Statin use within 30 days prior to Baseline or anticipated to occur during
study.
7. Rituximab use within 90 days prior to Baseline or anticipated to occur
during study.
NOTE: In subjects who received rituximab more than 90 days but less than 6
months prior to
Baseline, prophylactic antibiotics (e.g., ciprofloxacin, erythromycin,
penicillin V) should be given
upon initiation of study drug until 6 months after the last rituximab dose.
8. Recent initiation of intravenous immunoglobulin (IVIG) (i.e., first cycle
administered less than 90
days prior to Baseline).
9. Plasma exchange within 4 weeks prior to Baseline or expected to occur during
the 8-week
Treatment Period.
10. Active malignancy (except curatively resected squamous or basal cell
carcinoma of the skin)
requiring surgery, chemotherapy, or radiation within the prior 12 months
(subjects with a history of
malignancy who have undergone curative resection or otherwise not requiring
treatment for at least
12 months prior to Screening with no detectable recurrence are allowed).
11. History of any significant medical, psychiatric disorder, or laboratory
abnormality that in the
opinion of the investigator would make the subject unsuitable for participation
in the study.
12. Participation in another concurrent clinical trial involving an
experimental therapeutic intervention
(participation in observational studies and/or registry studies is permitted).
13. Unable or unwilling to comply with the requirements of the study.
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 | EUCTR201900149729-NL |
| ClinicalTrials.gov | NCT04025632 |
| CCMO | NL72130.018.19 |