The primary objective of this study is to evaluate the performance of the Navigate Anti-AAV9 Antibody Assay using serum specimens in subjects with SMA in Novartis clinical studies COAV101B12301 *STEER* and COAV101B12302 *STRENGTH*.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to evaluate the performance of the
Navigate Anti-AAV9 Antibody Assay using serum specimens in subjects with SMA in
Novartis clinical studies COAV101B12301 *STEER* and COAV101B12302 *STRENGTH*.
The primary measures of performance for the Navigate Assay are linked to the
primary and secondary endpoints of Novartis clinical studies COAV101B12301
*STEER* and COAV101B12302 *STRENGTH*:
STEER Primary Objective:
EFFICACY: To compare the efficacy of OAV101 IT vs. sham control as measured by
the change from baseline in HFMSE total score
STRENGTH Primary Objective:
To characterize the safety and tolerability of OAV101 IT over a 52-week period
in patients with SMA aged 2 to 12 years who have discontinued treatment with
nusinersen (Spinraza®) or risdiplam (Evrysdi®).
Secondary outcome
NA
Background summary
Since OAV101 is a non-replicating recombinant AAV9 virus containing the human
SMN complementary deoxyribonucleic acid (cDNA), the presence of anti-AAV9
antibodies in SMA patients should be tested to determine eligibility for
treatment with OAV101. Previous exposure to naturally occurring (wild type)
AAVs results in preexisting immunity that can potentially compromise transgene
expression by blocking transduction. It has been suggested that this could
limit therapeutic efficacy and raise potential safety concern (Mendell et al
2022). Immunity developed in seronegative patients after gene transfer may also
limit the ability to re-administer treatment if necessary.
According to several clinical studies, (Day et al 2021), patients of various
ages express AAV9 antibodies. The incidence of preexisting Abs in the general
population tends to increase with age, but not everybody develops anti-AAV Abs.
Immunity to AAV is often generated in childhood by the age of 2 years (Calcedo
et al 2011). Several studies have reported on the prevalence of anti-AAV9
antibodies in the pediatric population that show low rates of prior exposure to
AAV9 (Harrington et al 2016, Fu et al 2017). .
The purpose of this interventional clinical performance study is to establish
or confirm aspects of device performance which cannot be determined by
analytical performance studies, literature and/or previous experience gained by
routine diagnostic testing. This information is used to demonstrate compliance
with the relevant general safety and performance requirements with respect to
clinical performance. The data obtained shall be used in the performance
evaluation process and be part of the clinical evidence for the device.
Novartis currently has two clinical trials for which an investigational
clinical trial assay (CTA) developed by Navigate will be used to detect
pre-existing anti-AAV9 antibodies in SMA patients (see Intended Purpose above).
Novartis has instituted anti-AAV9 antibody testing in prior OAV101 studies in
order to exclude patients with antibody titer levels of > 1:50 titer by ELISA.
Based on the validation studies performed on the Navigate anti-AAV9 Antibody
Assay, a titer of >100 will be used in this assay for exclusion of the patients
as this titer correlates to the >1:50 by ELISA.
Study objective
The primary objective of this study is to evaluate the performance of the
Navigate Anti-AAV9 Antibody Assay using serum specimens in subjects with SMA in
Novartis clinical studies COAV101B12301 *STEER* and COAV101B12302 *STRENGTH*.
Study design
There will be one testing site located in the US: Navigate BioPharma Services,
Inc., A Novartis Subsidiary conducting the Navigate Anti-AAV9 Antibody Assay.
Informed consent regarding diagnostic testing, sample collection for diagnostic
testing and patient enrollment are conducted under the drug clinical trials
COAV101B12301 *STEER* and COAV101B12302 *STRENGTH*. The conduct of the Navigate
Assay testing at Navigate BioPharma is an essential part of the drug clinical
trials and is addressed within the protocol and informed consent materials.
Navigate Anti-AAV9 Antibody Assay will be utilized in support of Novartis
studies: COAV101B12301 *STEER* and COAV101B12302 *STRENGTH* at a single testing
facility in the United States, Navigate BioPharma Services, which is certified
by the College of American Pathologists based on Clinical Laboratory
Improvement Act.
Specimen testing will be performed in accordance with this protocol and the
following assay work instruction, A_WI-10060, Qualitative Determination of
Antibodies to Adeno-associated Virus Serotype 9 (AAV9) in Human Serum Using a
Bridging Electrochemiluminescent (ECL) Assay.
Intervention
NA
Study burden and risks
NA
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
STRENGTH Inclusion Criteria
* Written informed consent
* SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations
and any copy of SMN2 gene
* Aged 2 < 18 years (screening visit must occur before the patient's 18th
birthday) at time of Screening Visit 1
* Have had at least four loading doses of nusinersen (Spinraza®) or at least 3
months of treatment with risdiplam (Evrysdi®) at Screening
* Must be able to sit independently but must never have taken steps
independently
* Diagnosed through newborn or neonatal screening or patients clinically
diagnosed must have age of clinical symptom onset < 18 months
* Meets age-appropriate institutional criteria for use of anesthesia/sedation
* Female participants who are sexually active or have reached menarche must
have a negative pregnancy test at Screening. Those females who are sexually
active must also agree to use highly effective methods of contraception.
Exclusion criteria
STRENGTH Exclusion Criteria
* Excluding SMA, any medical condition considered clinically significant
* Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis
* Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an
immunoassay is reported as elevated at Screening (reference to >1:50 or a
validated result consistent with being elevated)
* Clinically significant abnormalities in test results during screening period
and/or at Baseline
* Platelet count less than the lower limit of normal (LLN), or platelet
transfusion within 1 month at Screening Visit 1
* Clinically significant abnormal coagulation panel results at Screening
* Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin
(TBL), gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH) >
upper limit of normal (ULN) at Screening (with the exception of isolated AST
elevation: in the absence of other liver laboratory abnormalities, isolated
elevated AST is not considered exclusionary)
* Contraindications for lumbar puncture procedure
* At Baseline (Day-1), participants are excluded if they received:
* nusinersen (Spinraza®) within 4 months at Baseline
* risdiplam (Evrysdi®) within 15 days at Baseline
* Vaccinations 2 weeks prior to administration of OAV101
* Hospitalization for a pulmonary event, or for nutritional support within 2
months prior to Screening or inpatient major surgery planned.
* Presence of the following:
* An active infectious process requiring systemic antiviral or antimicrobial
therapy up to 30 days prior to OAV101 administration, or
* An active but untreated viral or bacterial infectious process up to 30 days
prior to administration of OAV101, or
* Any febrile illness up to 30 days prior to administration of OAV101
* Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours
during a 24-hour period, noninvasive ventilation for >12 hours during a 24-hour
period or requiring tracheostomy, at Screening and up to OAV101 administration
* Concomitant use of any of the following medication categories within 90 days
prior to administration of OAV101
* Ongoing systemic immunosuppressive therapy (e.g., corticosteroids,
cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous
immunoglobulin, rituximab), plasmapheresis, immunomodulators (e.g., adalimumab)
* History of hypersensitivity to any of the study treatments or its excipients
or drugs of similar chemical classes
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 | 2023-A00403-42 |
| CCMO | NL84835.000.23 |