Phase 3 Trial to Evaluate OAV-101 Intrathecal (IT) in People with SMA
17 August 2021
The Food and Drug Administration (FDA) in the US, has removed the partial clinical trial hold initiated in October 2019 and determined that Novartis Gene Therapies’ investigational compound OAV-101 IT clinical trial for people with SMA may proceed. Novartis now plans to initiate a new global Phase 3 registration-enabling study (STEER trial) to evaluate the clinical efficacy, safety and tolerability of OAV-101 IT in treatment naïve people with SMA who are between two and 18 years of age, able to sit, but have never walked. OAV-101 IT contains the same active ingredient as onasemnogene abeparvovec (Zolgensma™), which is approved for intravenous use.
STEER is a randomised, double-blind, sham-controlled study. More than 100 people will be randomised to receive OAV-101 by IT injection or to receive a sham procedure. At the end of the 52-week period, all eligible patients who received the sham procedure will receive OAV-101 IT and all eligible patients who received OAV-101 IT will receive the sham procedure. This trial will add to the body of clinical data and emerging real-world evidence for the use of gene therapy to treat SMA.
A sham-controlled study - which means one groups receives a placebo - would be unethical in countries where treatments are available. For this reason this trial will not operate in the UK or mainland Europe. It will be offered in countries where no treatments are available.
About the STEER Trial
STEER is a Phase 3 randomised, double-blind, sham-controlled study to evaluate the clinical efficacy, safety, and tolerability of a one-time intrathecal (IT) dose of OAV-101 in treatment naïve patients with Type 2 SMA who are between two and 18 years of age, able to sit, but have never walked.
The primary objective of STEER is to evaluate the efficacy of one-time IT administration of OAV-101 IT compared to sham control over a 52-week period, at the end of which patients in the control arm will be treated with OAV-101 IT. The therapeutic effect of OAV-101 IT will be evaluated using a test to measure motor function, the Hammersmith Functional Motor Scale-Expanded (HFMSE).
Secondary objectives include evaluation of safety and the efficacy of one-time IT administration of OAV-101 using a test to measure upper limb function, the Revised Upper Limb Module (RULM) scale.
Questions & Answers from the Novartis Gene Therapies Team
1. Are you confident in OAV-101 IT as a potential treatment option for patients with SMA?
A.1. STEER will build upon promising data from the Phase 1/2 STRONG study, which to date has shown that treatment with OAV-101 IT led to significant increases in HFMSE scores and a clinically meaningful response. We believe that investigational OAV-101 IT is a viable potential treatment path for older patients with SMA and for whom a single-dose, treatment option could be especially compelling.
2. Where will you be recruiting patients for this study?
A.2. Study plans for STEER are still being finalised. For more information about the study, contact the Novartis Gene Therapies Medical Information team at firstname.lastname@example.org It is important to clarify that enrolment is not anticipated to start until later this year.
3. Why does the STEER trial use a sham control?
A.3. The use of a sham control offers an optimal chance of obtaining clear data that would allow for approval to treat more segments of the community.
4. How did the results from the STRONG study inform the clinical trial design of STEER?
A.4. STEER will build upon the Phase 1/2 STRONG study which showed that treatment with OAV-101 IT led to significant increases in HFMSE scores and a clinically meaningful response in older patients ≥2 years and <5 years old with SMA Type 2.