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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogen Idec Research Limited

Participant type

Pediatric, Patients, Healthy volunteers

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 Jul 2023 → ongoing

Decision date (initial)

2024-05-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Biogen Idec Research Limited

External identifiers

EU CT number

2023-505643-39-00

EudraCT number

2022-000956-12

ClinicalTrials.gov

NCT05575011

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety, Pharmacodynamic, Dose response

The primary objective of the study is to assess the safety and tolerability of BIIB115 administered via intrathecal (IT) bolus injection to healthy participants in Part A, pediatric participants with Spinal Muscular Atrophy (SMA) who have previously received onasemnogene abeparvovec in Part B, and to participants who complete Part B in Part B LTE.

Secondary objectives 1

1. The secondary objectives of the study is to evaluate the pharmacokinetics (PK) of BIIB115 in Parts A, B, and B LTE.

Conditions and MedDRA coding

Spinal muscular atrophy

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Infarmed, Medicines Evaluation Board

Plan to share IPD

Yes

IPD plan description

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Part A - Male healthy participants aged 18 to 55 years, inclusive.
2. Part B - Potential for improvement due to suboptimal clinical status secondary to SMA, as determined by the Investigator.
3. Part B LTE - Completion of the assessments in Part B
4. Part A - Have a body mass index of 18 to 30 kilograms per meter square (kg/m^2), inclusive.
5. Part A - Must be in good health as determined by the investigator, based on medical history and screening evaluations.
6. Part B - Age 0.5 to 12 years old, inclusive, at the time of informed consent.
7. Part B - Weight ≥7 kg at the time of informed consent.
8. Part B - Genetic diagnosis of SMA (5q SMA homozygous survival motor neuron 1 (SMN1) gene deletion or mutation or compound heterozygous mutation).
9. Part B - Survival motor neuron 2 (SMN2) copy number ≥1.
10. Part B - Must have received intravenous (IV) onasemnogene abeparvovec per the approved label or per guidelines including the steroid regimen and monitoring specified therein.
11. Part B - Treatment with onasemnogene abeparvovec ≥180 days prior to first BIIB115 dose.
12. Part B LTE - Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures (as assessed by the Investigator and either anesthesiologist or pulmonologist).

Exclusion criteria 16

1. 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.
2. Part B - Treatment with any SMN2-splicing modifier (nusinersen or risdiplam) after receiving onasemnogene abeparvovec. Treatment with nusinersen <12 months from the first dose of BIIB115.
3. Part B - 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.
4. Part B - Permanent ventilation, defined as tracheostomy or ≥16 hours ventilation /day continuously for >21 days in the absence of an acute reversible event.
5. Part B LTE - Any new condition or worsening of an existing condition that, according to the Investigator, would make the participant unsuitable for inclusion, could interfere with the assessment of safety, or would compromise the ability of the participant to undergo study procedures.
6. Part A - 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.
7. Part A - Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening or between screening and Day -1.
8. Part A - 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.
9. Part B - Severe or serious AEs related to onasemnogene abeparvovec therapy that are ongoing during Screening.
10. Part B - Interval of <180 days between onasemnogene abeparvovec therapy and first BIIB115 dose.
11. Part B - Ongoing steroid treatment following onasemnogene abeparvovec at time of screening.
12. Part B - History of drug induced liver injury or liver failure per Hy’s law definition.
13. Part B - History of thrombotic micrangiopathy.
14. Clinically significant abnormalities in hematology, blood chemistry parameters, or electrocardiograms (ECGs) prior to first LTE visit that would make the participant unsuitable for inclusion as assessed by the Investigator.
15. Treatment with an approved SMN2-splicing modifier (nusinersen or risdiplam)
16. Other protocol-defined Inclusion/Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Parts A, B and Long Term Extension (LTE): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Part A: Up to Day 393, Part B: Up to Day 720; Part B LTE: Up to Day 2520]

Secondary endpoints 8

1. Parts A,B and B LTE: Concentration of BIIB115 in Cerebral Spinal Fluid (CSF) [Time Frame: Part A: Day 1 to Day 180, Part B: Days 1 and 720; Part B LTE: Day 720 to Day 2520].
2. Part A: Terminal Elimination Half-Life (t½) of BIIB115 in CSF. [Time Frame: Day 1 to Day 180].
3. Parts A,B and B LTE: Concentration of BIIB115 in Serum [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to 720; Part B LTE: Day 720 to Day 2520].
4. Parts A and B: Terminal Elimination Half-Life (t½) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].
5. Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-last) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].
6. Parts A and B: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].
7. Parts A and B: Maximum Observed Concentration (Cmax) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].
8. Parts A and B: Time to Reach Maximum Observed Concentration (Tmax) of BIIB115 in Serum. [Time Frame: Part A: Day 1 to Day 180, Part B: Day 1 to Day 720].

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biogen Idec Research Limited

Sponsor organisation

Biogen Idec Research Limited

Address

Building 5 Foundation Park, Roxborough Way Roxborough Way

City

Maidenhead

Postcode

SL6 3UD

Country

United Kingdom

Scientific contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Third parties 14

Locations

6 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

5 submissions — initial application plus substantial / non-substantial modifications