A Study to Evaluate Safety, Tolerability, and Distribution of a Microdose of Radiolabeled BIIB067 (99mTc-MAG3-BIIB067) Co-administered With BIIB067 (Tofersen) to Healthy Adults

NCT03764488 | Completed Phase 1 FDA Drug

• 1 other identifier: 233HV101
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of the study is to evaluate the distribution in the central nervous system (CNS) of a microdose 99mTc-MAG3-BIIB067 co-administered with unlabeled BIIB067 (Tofersen). The secondary objective of the study is to assess the safety and tolerability of unlabeled BIIB067 co-administered with a microdose of 99mTc-MAG3-BIIB067 to healthy participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• BIIB067 Concentrations Throughout the CNS

  BIIB067 concentrations throughout the CNS will be estimated by single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of 99mTc-MAG3-BIIB067.

  1 to 24 hours post-dose on Day 1

Secondary Outcomes (2)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 91

• Dose of Radiation Absorbed (Dosimetry) in Specific Regions of the CNS

  1 to 24 hours post-dose on Day 1

Study Arms (4)

BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF

EXPERIMENTAL

Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 15 milliliter (mL) artificial cerebrospinal fluid (aCSF).

Drug: Tofersen; Drug: 99mTc-MAG3-BIIB067

BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF

EXPERIMENTAL

Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 15 mL aCSF.

Drug: Tofersen; Drug: 99mTc-MAG3-BIIB067

BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF

EXPERIMENTAL

Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 5 mL aCSF.

Drug: Tofersen; Drug: 99mTc-MAG3-BIIB067

BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF

EXPERIMENTAL

Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in up to 20 mL aCSF.

Drug: Tofersen; Drug: 99mTc-MAG3-BIIB067

Interventions

Tofersen DRUG

Administered as specified in the treatment arm.

Also known as: BIIB067, QALSODY

BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF; BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF; BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF; BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF

99mTc-MAG3-BIIB067 DRUG

Administered as specified in the treatment arm.

BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF; BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF; BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF; BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a body mass index between 18 and 30 kilogram per square meter (kg/m\^2), inclusive.
• All men must practice highly effective contraception during the study and for 5 months after their last dose of study treatment.
• All female participants must be of non-childbearing potential and must meet 1 of the following criteria to participate in the study: a. Postmenopausal, b. History of bilateral oophorectomy (performed at least 6 weeks prior to Screening), c. History of hysterectomy (performed at least 6 weeks prior to Screening), or d. History of female surgical sterilization (e.g., bilateral tubal ligation; performed at least 6 weeks prior to Screening).

You may not qualify if:

• History of or ongoing clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator.
• Clinically significant abnormal laboratory test values, as determined by the Investigator, at Screening or Check-in.
• Use of any prescription medication, over-the-counter medication (e.g., aspirin and nonsteroidal anti-inflammatory drugs \[excluding acetaminophen\]), or dietary and herbal supplements (e.g., St. John's wort) within 28 days of Check-in and an unwillingness to refrain from use through end of study (i.e., through the Day 91 visit), unless specifically permitted elsewhere within the protocol.
• Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 30 days (6 months for biologics) or 5 half-lives, whichever is longer, prior to Check-in.
• History or physical examination that could be suggestive of a medical or mechanical condition, disorder, or disease that could represent a relative contraindication to lumbar puncture (LP), including but not limited to: (a) medication use that prolongs coagulation times, including aspirin; (b) known disorders of the coagulation cascade, platelet function, or platelet count; (c) low white blood cell counts; (d) chronic low back pain; (e) prior lumbar spine surgery; (f) anatomical factors at or near the LP site; (g) clinical signs of raised intracranial pressure (e.g., headache, papilledema, or focal neurologic signs).
• Contraindications to radiation exposure for research purposes.
• Exposure to ionizing radiation within the last 12 months that would result in approaching the exposure limits for healthy volunteers.

Sponsors & Collaborators

• Biogen: lead

Study Sites (2)

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

tofersen

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 5, 2018
• Study Start: December 20, 2018
• Primary Completion: June 10, 2021
• Study Completion: July 10, 2021
• Last Updated: June 22, 2023

Record last verified: 2023-06

Locations

US (2)