This study has been transitioned to CTIS with ID 2024-511654-42-00 check the CTIS register for the current data. -Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA-Evaluate the long-term efficacy of…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Incidence of TEAEs and SAEs by severity
Secondary outcome
- Hammersmith Functional Motor Scale Expanded (HFMSE) total score at
prespecified time points (excludes TOPAZ Cohort 1 patients)
- Revised Upper Limb Module (RULM) total score at prespecified time points
(excludes TOPAZ Cohort 1 patients)
- Number of World Health Organization (WHO) motor development milestones
attained at prespecified time points (excludes TOPAZ
Cohort 1 patients)
- Revised Hammersmith Scale (RHS) total score and results for 6-Minute Walk
Test, 30-Second Sit-to-Stand, 10-Meter Walk/Run (from the
RHS), and timed rise from floor (from the RHS) at prespecified time points
(TOPAZ Cohort 1 patients only)
-Presence or absence of antidrug antibody (ADA) against apitegromab in serum
from blood samples
Background summary
SMA is a whole-body disease (Wirth 2020). Although the SMN upregulator (also
referred to as SMN corrector) therapies approved
for the treatment of SMA have been shown to significantly improve clinical
outcomes by preventing or reducing the decline in motor
function, patients may continue to suffer from substantial motor functional
impairment because targeted SMN upregulator therapies
focus on SMN-dependent pathways and do not directly impact skeletal muscle to
reverse the atrophy that has already taken place
(Mercuri 2018, Mercuri 2020).
Consequently, there remains an unmet medical need for a complementary
therapeutic strategy, namely muscle-directed therapy,
that may address muscle atrophy and thereby improve motor function in patients
with SMA. Through its novel mechanism of action
as a selective inhibitor of
myostatin activation, apitegromab (SRK-015) has the potential to produce a
clinically meaningful effect on motor function in a broad
population of patients with SMA who are being treated with background SMN
upregulator therapies (e.g., nusinersen [SPINRAZA®]
or risdiplam [EVRYSDI®]) (SPINRAZA Food and Drug Administration [FDA]
Prescribing Information [PI] 2020, SPINRAZA Summary
of Product Characteristics [SmPC] 2021,
EVRYSDI FDA PI 2021, EVRYSDI SmPC 2021).
Study objective
This study has been transitioned to CTIS with ID 2024-511654-42-00 check the CTIS register for the current data.
-Evaluate the long-term safety and tolerability of apitegromab in patients with
Type 2 and Type 3 SMA
-Evaluate the long-term efficacy of apitegromab by assessing changes in motor
function outcome measures at prespecified time points
-Further evaluate the immunogenicity of apitegromab
Study design
This Phase 3 trial will continue to evaluate the safety and efficacy of
apitegromab in ambulatory and nonambulatory patients with Type 2 and Type 3 SMA
who have completed a previous apitegromab trial (i.e., TOPAZ or SAPPHIRE). This
global trial will be conducted at approximately 55 trial sites.
The trial will include Baseline, Treatment, and Safety Follow-up Periods.
Approximately 260 male and female patients who are >=2 years of age with Type 2
and Type 3 SMA will receive apitegromab 20 mg/kg every 4 weeks by intravenous
(IV) infusion during the 104-week Treatment Period. Dosing every 4 weeks should
be targeted. However, a ±7*day window around each
dosing visit (with a minimum of 21 days and a maximum of 35 days between doses)
is allowed without consultation with the Sponsor.
Intervention
N/A
Study burden and risks
- The study lasts a total of approximately 76 weeks for patients.
- Additional hospital visits, additional physical tests, including a pregnancy
test.
- A total of approximately 110ml of blood is taken. This amount is not a
problem (for comparison: a blood donation means that 500 ml of blood is taken
each time). Possible side effects of blood tests include fainting, soreness and
tenderness at the injection site and, in rare cases, infection.
- If the study drug does not work for the patient, he/she may see an increase
in his/her disease symptoms.
Binney Street 3rd Floor 301
Cambridge MA 02142
US
Binney Street 3rd Floor 301
Cambridge MA 02142
US
Listed location countries
Age
Inclusion criteria
1. Informed consent document signed by the patient if the patient is legally an
adult. If the patient is legally a minor, informed consent document signed by
the patient's parent or legal guardian and patient's oral or written assent
obtained, if applicable and in accordance with the regulatory and legal
requirements of the participating location.
2. Patients who have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or
the Phase 3 SAPPHIRE (Study SRK-015-003) trial.
3. Estimated life expectancy >2 years from Baseline (Day 1).
4. Able to receive study drug infusions and provide blood samples through the
use of a peripheral IV or a long-term IV access device that the patient has
placed for reasons independent from the trial (i.e., for background medical
care and not for the purpose of receiving apitegromab in the trial), throughout
the trial.
5. Able to adhere to the requirements of the protocol.
6. Females of childbearing potential must have a negative pregnancy test at
Baseline and agree to use at least 1 acceptable method of contraception
throughout the trial and for 20 weeks after the last dose of apitegromab.
Female patients who are expected to have reached reproductive maturity by the
end of the trial must agree to adhere to trial-specific contraception
requirements.
Exclusion criteria
1. Patient permanently discontinued study treatment during the feeder trial
(i.e., TOPAZ or SAPPHIRE).
2. Nutritional status that was not stable over the past 6 months and is not
anticipated to be stable throughout the trial or medical necessity for
a gastric/nasogastric feeding tube, where the majority of feeds are given by
this route, as assessed by the investigator.
3. Patient is currently enrolled in any investigational drug trial other than
TOPAZ or SAPPHIRE.
4. Prior history of severe hypersensitivity reaction or intolerance to
SMNtargeted therapies.
5. Prior history of severe hypersensitivity reaction or intolerance to
apitegromab.
6. Use of chronic daytime noninvasive ventilatory support for >16 hours daily
in the 2 weeks before dosing, or anticipated to regularly receive
such daytime ventilator support chronically throughout the trial.
7. Any acute or comorbid condition interfering with the well-being of the
patient at the patient's last visit in TOPAZ or SAPPHIRE, including active
systemic infection, the need for acute treatment, or inpatient observation due
to any reason.
8. Pregnant or breastfeeding.
9. Any other condition or clinically significant laboratory result or ECG value
that, in the opinion of the Investigator, may compromise safety or
compliance, would preclude the patient from successful completion of the trial,
or interfere with the interpretation of the results.
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 |
|---|---|
| Other | 202200177114 |
| EU-CTR | CTIS2024-511654-42-00 |
| EudraCT | EUCTR2022-001771-14-NL |
| CCMO | NL82994.028.22 |