A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB115

Healthy Volunteer Clinical Trial

Official title:

A Randomized, Blinded, Placebo-Controlled, Phase 1 Single Ascending Dose Study in Healthy Adult Male Volunteers and an Open-Label Multiple Ascending Dose Study in Pediatric SMA Participants Previously Treated With Onasemnogene Abeparvovec (Zolgensma™) to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB115

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05575011
• Other study ID #: 277HV101
• Secondary ID: 2022-000956-12
• Status: Recruiting
• Phase: Phase 1
• Start date: October 10, 2022
• Est. completion date: September 1, 2027

Study information

• Verified date: May 2024
• Source: Biogen
• Contact: US Biogen Clinical Trial Center
• Phone: 866-633-4636
• Email: clinicaltrials[@]biogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the safety and tolerability of single ascending dose of BIIB115 administered via intrathecal (IT) bolus injection to healthy male participants in Part A and multiple ascending doses of BIIB115 administered via IT bolus injection to pediatric Spinal Muscular Atrophy (SMA) participants previously treated with onasemnogene abeparvovec in Part B. The secondary objective of the study is to evaluate the pharmacokinetics (PK) of single-dose of BIIB115 administered via IT bolus injection to healthy male participants in Part A and multiple ascending doses of BIIB115 administered via IT bolus injection to pediatric SMA participants who previously received onasemnogene abeparvovec in Part B.

Description:

This is a first-in-human (FIH) study to evaluate the safety, tolerability, and PK of BIIB115, and consists two parts.

Part A includes cohorts 1 through 4, where healthy volunteer (HV) participants will be assigned to receive a single dose of either BIIB115 or placebo. This part will have a 4-week Screening Period, a Treatment Period, and a 13-month Follow-up Period. The study duration for each participant will be approximately 14 months.

Part B includes cohorts 5 and 6, where pediatric participants with SMA will be assigned to receive 2 doses of BIIB115. This part will have a 4-week Screening Period, a Treatment Period, and a 24-month Follow-up Period. The study duration for each participant will be approximately 25 months.

The study will be conducted in approximately 20 sites globally.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: September 1, 2027
• Est. primary completion date: September 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 55 Years

Eligibility

Key Inclusion Criteria:

Part A:

• Male healthy participants aged 18 to 55 years, inclusive

• Have a body mass index of 18 to 30 kilograms per meter square (kg/m^2), inclusive

• Must be in good health as determined by the investigator, based on medical history and screening evaluations

Part B:

• Age 0.5 to 12 years old, inclusive, at the time of informed consent

• Weight =7 kg at the time of informed consent

• Genetic diagnosis of SMA (5q SMA homozygous survival motor neuron 1 (SMN1) gene deletion or mutation or compound heterozygous mutation)

• Survival motor neuron 2 (SMN2) copy number =1

• Must have received intravenous (IV) onasemnogene abeparvovec per the approved label or per guidelines including the steroid regimen and monitoring specified therein

• Treatment with onasemnogene abeparvovec =180 days prior to first BIIB115 dose

• Potential for improvement due to suboptimal clinical status secondary to SMA, as determined by the Investigator

Key Exclusion Criteria:

Part A:

• Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from multiple lumbar puncture (LP) procedures required for dosing and CSF collection, per the investigator discretion

• History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator

• Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening or between screening and Day -1

• Current enrollment or a plan to enroll in any interventional clinical study of a drug, biologic, or device, in which an investigational treatment or approved therapy for investigational use is administered within 3 months (or 5 half-lives of the agent, whichever is longer) prior to randomization

Part B:

• Severe or serious AEs related to onasemnogene abeparvovec therapy that are ongoing during Screening

• Interval of <180 days between onasemnogene abeparvovec therapy and first BIIB115 dose

• Ongoing steroid treatment following onasemnogene abeparvovec at time of screening

• History of drug induced liver injury or liver failure per Hy's law definition

• History of thrombotic micrangiopathy

• Treatment with any SMN2-splicing modifier (nusinersen or risdiplam) after receiving onasemnogene abeparvovec. Treatment with nusinersen <12 months from the first dose of BIIB115.

• Any reason, anatomical or otherwise (including abnormal hematology/coagulation), that presents increase of risk of complication from the LP procedures, CSF circulation, or safety assessments, including a history of hydrocephalus or implanted shunt for CSF drainage.

• Permanent ventilation, defined as tracheostomy or =16 hours ventilation /day continuously for >21 days in the absence of an acute reversible event

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Healthy Volunteer
• Muscular Atrophy
• Muscular Atrophy, Spinal

Intervention

Drug:
• BIIB115
Administered as specified in the treatment arm
• BIIB115-Matching Placebo
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Children's Hospital of Eastern Ontario	Ontario
France	Hôpital Armand Trousseau	Paris
Germany	Universitatsklinikum Essen	Essen
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Israel	Schneider Children's Medical Center	Petach-Tikvah
Italy	Fondazione Serena Onlus - Centro Clinico Nemo	Milano
Italy	Pediatric Neurology Unit, Catholic University	Rome
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Centre For Human Drug Research	Leiden
Netherlands	UMC Utrecht	Utrecht
Poland	Instytut Centrum Zdrowia Matki Polki Dept of Neurology	Lodz
Poland	Instytut "Pomnik - Centrum Zdrowia Dziecka	Warsaw
Poland	PRATIA S.A. MTZ Clinical Research Powered by Pratia	Warszawa
United Kingdom	Great Ormond Street Hospital for Children	Bloomsbury
United Kingdom	Sheffield Childrens Hospital	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.; A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.	Part A: Up to Day 393, Part B: Up to Day 720
Secondary	Parts A and B: Concentration of BIIB115 in Cerebral Spinal Fluid (CSF)		Part A: Day 1 to Day 180, Part B: Days 1 and 360
Secondary	Part A: Terminal Elimination Half-Life (t½) of BIIB115 in CSF		Day 1 to Day 180
Secondary	Parts A and B: Concentration of BIIB115 in Serum		Part A: Day 1 to Day 180, Part B: Day 1 to 720
Secondary	Parts A and B: Terminal Elimination Half-Life (t½) of BIIB115 in Serum		Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Secondary	Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-last) of BIIB115 in Serum		Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Secondary	Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB115 in Serum		Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Secondary	Parts A and B: Maximum Observed Concentration (Cmax) of BIIB115 in Serum		Part A: Day 1 to Day 180, Part B: Day 1 to Day 720
Secondary	Parts A and B: Time to Reach Maximum Observed Concentration (Tmax) of BIIB115 in Serum		Part A: Day 1 to Day 180, Part B: Day 1 to Day 720