An open-label study to investigate the safety, tolerability, and Pharmacokinetics/Pharmacodynamics of risdiplam (RO7034067) in adult and pediatric patients with spinal muscular atrophy
- Conditions
- Spinal muscular athrophygenetic progressive neuromuscular disease characterized by profound weakness and muscle atrophy10028396
- Registration Number
- NL-OMON49730
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
1. Males and females 6 months to 60 years of age inclusive (at screening)
2. Confirmed diagnosis of 5q-autosomal recessive SMA, including:
- Genetic confirmation of homozygous deletion or heterozygosity predictive of
loss of function of the SMN1 gene.
- Clinical history, signs, or symptoms attributable to SMA.
3. Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier
RO6885247 or previous treatment with any of the following:
- Nusinersen (defined as having received >=4 doses of nusinersen, provided that
the last dose was received >= 90 days prior to screening)
- Olesoxime (provided that the last dose was received <= 18 months and >= 90 days
prior to screening)
- AVXS-101 (provided that the time of treatment was >= 12 months prior to
screening)
4. Able and willing to provide written informed consent and to comply with the
study protocol according to International Conference on Harmonization (ICH) and
local regulations. Alternatively, a legally authorized representative must be
able to give consent for the patient according to ICH and local regulations and
assent must be given whenever possible.
5. Adequately recovered from any acute illness at the time of screening and
considered well enough to participate in the opinion of the Investigator.
6. For women of childbearing potential: negative blood pregnancy test at
screening, agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and agreement to refrain from
donating eggs, as defined below:
- Women must remain abstinent (refrain from heterosexual intercourse) or use
two adequate methods of contraception, including at least one method with a
failure rate of < 1% per year, during the treatment period and for at least 28
days after the final dose of study drug. Women must refrain from donating eggs
during this same period.
- A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months
of amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization (removal of ovaries and/or uterus). The
definition of childbearing potential may be adapted for alignment with local
guidelines or regulations.
- Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, established and proper
use of hormonal contraceptives that inhibit ovulation, hormone-releasing
intrauterine devices, and copper intrauterine devices.
- A vasectomy is a highly effective birth control method provided that the
partner is the sole sexual partner of the woman of child bearing potential
trial participant, and provided the vasectomized partner has received medical
assessment of the surgical success.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post-ovulation methods) and withdrawal are not acceptable methods of
contraception. If required per local guidelines or regulations, locally
recognized acceptable methods of contraception and information about the
reliability of abstinence will be described in the local Informed Co
1. Inability to meet study requirements.
2. Concomitant participation in any investigational drug or device study.
3. With the exception of studies of olesoxime, AVXS-101, or nusinersen:
Previous participation in any investigational drug or device study within 90
days prior to screening, or 5 half-lives of the drug, whichever is longer.
4. Any history of gene or cell therapy, with the exception of AVXS-101.
5. Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular
system diseases as considered to be clinically significant by the Investigator.
6. Inadequate venous or capillary blood access for the study procedures, in the
opinion of the Investigator.
7. For patients aged < 2 years, hospitalization for a pulmonary event within 2
months prior to screening and pulmonary function not fully recovered at the
time of screening.
8. Lactating women.
9. Suspicion of regular consumption of drugs of abuse.
10. For adults and adolescents only, i.e., aged > 12 years, positive urine test
for drugs of abuse or alcohol at screening or Day -1 visit.
11. Cardiovascular, blood pressure, and heart rate:
- Adults: Sustained resting systolic blood pressure (SBP) > 140 mmHg or < 80
mmHg, and/or diastolic blood pressure (DBP) > 90 mmHg or <40 mmHg; a resting
heart rate < 45 bpm or > 100 bpm if considered to be clinically significant by
the Investigator.
- Adolescents (12*17 years of age): SBP and/or DBP outside the 95th percentile
for age; resting heart rate < 50 bpm or > 100 bpm if considered to be
clinically significant by the Investigator.
- Children (6*11 years of age): SBP and/or DBP outside the 95th percentile for
age; resting heart rate < 60 bpm or > 120 bpm, if considered to be clinically
significant by the Investigator.
- Children (2*5 years of age): SBP and/or DBP outside the 95th percentile for
age; resting heart rate < 70 bpm or > 140 bpm if considered to be clinically
significant by the Investigator.
- Children (6 months to < 2 years of age): SBP and/or DBP outside the 95th
percentile for age; resting heart rate <70 bpm or > 170 bpm, if considered to
be clinically significant by the Investigator.
12. Presence of clinically significant ECG abnormalities before study drug
administration (e.g., second or third degree AV block, confirmed QTcF >460 msec
for patients aged >= 10 years, or QTcB > 460 ms for children up to age 10 years
(Bazett*s correction is more appropriate in young children) from the average of
triplicate measurements, or cardiovascular disease (e.g., cardiac
insufficiency, coronary artery disease, cardiomyopathy, congestive heart
failure, family history of congenital long QT syndrome, family history of
sudden death) indicating a safety risk for the patient as determined by the
Investigator.
13. History of malignancy if not considered cured.
14. For patients aged > 6 years, significant risk for suicidal behavior in the
opinion of the Investigator, as assessed by the Columbia-Suicide Severity
Rating Scale (C-SSRS).
15. Any major illness within 1 month before the screening examination or any
febrile illness within 1 week prior to screening and up to first dose
administration
16. Use of any OCT-2 and MATE substrates within 2-weeks before dosing
(including but not limited to: amantadine, cimetidine, memantine, amiloride,
famotidine, metf
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method