Spinal Muscular Atrophy (SMA) MedDRA version: 20.1 Level: PT Classification code 10041582 Term: Spinal muscular atrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Biohaven Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Written Informed Consent a. Written informed consent/assent must be obtained from the participant in accordance with requirements of the study center’s institutional review board (IRB) or ethics committee, prior to the initiation of any protocol-required procedures. b. As applicable according to age, the participant is able to understand the Informed Assent Form (IAF) and the participant’s parent(s)/legal representative(s) (according to local regulations) are/is able to read and understand the Informed Consent Form (ICF). c. The participant has signed the IAF and the participant’s parent(s)/legal representative(s) (according to local regulations) have/has signed the ICF prior to the conduct of any study-specific procedures, as applicable according to age. d. The participant and the participant’s parent(s)/legal representative(s) (as required according to local regulations) are/is willing and able to attend protocol-specified study appointments within the specified time windows. e. The participant must be able to understand and follow instructions and be willing to complete all assessments under supervision of legal representative(s) as required by the protocol. Study BHV2000-301 Clinical Protocol, Version 4.0 Confidential Taldefgrobep alfa Page 40 of 80 2. Participants must agree to provide all requested demographic information (i.e. gender, race). 3. Target Population a. Male and female participants ?4 years to ?21 years of age at the time of Screening. b. Spinal Muscular Atrophy confirmed by genetic diagnosis of 5q-autosomal recessive SMA as well as SMN2 copy number (genetic diagnosis and SMN2 copy number confirmed with documentation either prior to enrollment from previous testing or confirmed during during study) c. Ambulant or non-ambulant i. Ambulant defined as: (1) Able to walk/run 10 meters in ?30 seconds at screening Participants who are unable to meet ambulatory criteria may still be enrolled if they meet other criteria but would be considered non-ambulant ii. Non-ambulant defined as all of the following: (1) Unable to able to walk/run 10 meters in ?30 seconds at screening; (2) Must be able to sit independently (sits up straight with head erect for at least 10 seconds; does not use arms or hands to balance body or support position); and (3) RULM entry item A score of ?2. d. Treated with an SMA disease-modifying therapy and anticipated to remain on that same treatment regimen and dose throughout the trial, including the following: i. a stable regimen of nusinersen for 6 months prior to Screening; ii. a stable regimen of risdiplam, for 6 months prior to Screening; and/or iii. a single dose of onasemnogene abeparvovec, received at least 2 years prior to Screening. e. MFM32 Total Score <90% out of 100% (achieved by a total mark raw score of =86 out of 96) at Screening f. Be able to complete all study procedures, measurements (including functional assessments) and visits and parent or guardian and participant has adequately supportive psychosocial circumstances, in the judgment of the Investigator Study BHV2000-301 Clinical Protocol, Version 4.0 Confidential Taldefgrobep alfa Page 41 of 80 g. Have an estimated life expectancy of greater than 2 years from Screening, in the judgment of the Investigator h. Must have reliable caregiver to accompany participant to study visits, with the consistency of caregiver completing the caregiver assessments at Baseline, Week 24 and Week 48/Early Discontinuation, w
Exclusion criteria
Exclusion criteria: 1. Participation in any other investigational clinical trial while participating in this clinical trial with the exception of registry and natural history studies regarding investigational drug trials. 2. Receiving or have received previous administration of anti-myostatin therapies 3. Weight <15 kg 4. Medical History and Concurrent Diseases a. Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for daytime treatment while awake (use overnight or during daytime naps is acceptable) Study BHV2000-301 Clinical Protocol, Version 4.0 Confidential Taldefgrobep alfa Page 42 of 80 b. Hospitalization for a pulmonary event within the last 2 months or planned hospitalization at the time of screening c. History of spinal fusion within 6 months prior to screening. Note: MAGEC rod nonsurgical adjustments are allowed during the study. d. Severe scoliosis and/or contractures at screening. Based on clinical judgment, any scoliosis or contractures present must be stable over the past 6 months, anticipated to be stable for the duration of the study and not prevent the participant from being evaluated on any functional outcome measures throughout the duration of the study e. Past surgery for scoliosis or hip fixation in the 6 months preceding screening or planned during the study. f. Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening g. Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period h. Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter i. History of bacterial meningitis j. Treatment with another investigational drug within 90 days prior to Screening or 5 halflives (whichever is longer). If treatment was with a currently approved medication, this timeframe is not applicable. If the participant is in a study for an approved medication that does not include procedures that could impact blinding (such as drawing blood for biomarkers), this can be assessed on a case by case basis. k. Ongoing medical condition that according to the Site Investigator would interfere with the conduct and assessments of the study. Examples are medical disability (e.g., wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures. l. The participant has reported current use of, or has tested positive at the Screening visit for, drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA, methamphetamines, oxycodone, phencyclidine (PCP). Detectable levels of these compounds are exclusionary with the following exception: i. Participants who are positive for amphetamines, and who are prescribed an amphetamine for an approved indication (e.g. ADHD) will be allowed into the study at the Investigator’s discretion. This determination by the Investigator must be well documented in the participant’s source medical records. The stimulant dose must be stable from 3 months prior to baseline until the end of treatment visit occurs. Study BHV2000-301 Clinical Protocol, Version 4.0 Confidential Taldefgrobep alfa Page 43 of 80 m. The participant has a history of cancer. n. Unstable gastrointestinal, renal, hepatic, endocrine, or cardi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of taldefgrobep alfa in participants who are already taking a stable dose of nusinersen or risdiplam or have a history of onasemnogene abeparvovec-xioi, compared to placebo, measured by change in the 32 item Motor Function Measure (MFM-32) total score between Baseline and Week 48;Secondary Objective: - To compare the efficacy of taldefgrobep alfa to placebo using the Revised Upper Limb Module (RULM). -To compare the efficacy of taldefgrobep alfa to placebo using the Revised Hammersmith Scale (RHS). -To assess the safety and tolerability of taldefgrobep alfa as reflected by new or worsening lab abnormalities, treatment-related adverse events (AEs), serious AEs, and AEs leading to discontinuation. ;Primary end point(s): Change from baseline in the MFM-32 at Week 48 ;Timepoint(s) of evaluation of this end point: Double blind phase: Baseline, visit 5, visit 6, visit 7, visit 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in the RULM at Week 48 - Change from baseline in the RHS at Week 48 - Frequency of unique subjects with: new or worsening lab abnormalities, treatment related adverse events, serious adverse events, and adverse events leading to discontinuation. ;Timepoint(s) of evaluation of this end point: Double blind phase: RULM: Baseline, visit 5, visit 6, visit 7, visit 8 RHS: Baseline, visit 5, visit 6, visit 7, visit 8 | — |
Countries
Belgium, Czech Republic, France, Germany, Italy, Poland, Spain
Contacts
Public ContactLia Donahue
Biohaven Pharmaceuticals, Inc
Outcome results
None listed