Study of ARO-DUX4 in Adult Patients With Facioscapulohumeral Muscular Dystrophy Type 1

March 12, 2024 updated by: Arrowhead Pharmaceuticals

A Phase1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DUX4 in Adult Patients With Facioscapulohumeral Muscular Dystrophy Type 1

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-DUX4 in participants with facioscapulohumeral muscular dystrophy Type 1 (FSHD1). In Part 1 of the study, participants will receive a single dose of ARO-DUX4 or placebo. In Part 2 of the study, participants will receive 2 or 4 doses of ARO-DUX4 or placebo. Participants who complete Part 1 will have the option to re-screen and re-randomize into Part 2. All participants will undergo pre- and post-dose MRI-guided muscle biopsies (a total of 2 biopsies). Participants who complete Part 1 and enroll in Part 2 will be required to undergo an additional screening biopsy. Participants completing Part 1 or Part 2 may have the option to continue to receive drug in an open-label extension study or may be eligible to participate in later-stage clinical studies.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

52

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • New Zealand
      • Auckland, New Zealand, 1010
        • Recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Genetically confirmed FSHD1 based on Screening evaluation or source verifiable medical record
  • Clinical severity score between 3 and 8 (scale, 0 to 10)
  • Must have eligible lower extremity muscle for biopsy as determined from MRI by a central reader
  • A 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety in the study
  • Participants of childbearing potential and their partners must use highly effective contraception during the study and for at least 12 weeks following the end of study or last dose of study medication, whichever is later. Males must not donate sperm during the study from Day 1 until at least 12weeks following the end of study or last dose of study medication, whichever is later.

Exclusion Criteria:

  • Human Immunodeficiency Virus (HIV) infection as shown by presence of anti-HIV antibody (seropositive) at Screening
  • Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening
  • Uncontrolled hypertension
  • Severe cardiovascular disease
  • History of thrombolic eve4nts
  • Platelet count less that the lower limit of normal at Screening
  • History or presence of: a hypercoagulable state, nephrotic range proteinuria, antiphospholipid antibody syndrome, myeloproliferative disease, inability to ambulate, use of hormone-based contraceptives.
  • Any contraindication to muscle biopsy or MRI

Note: additional inclusion/exclusion criteria may apply per protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ARO-DUX4
ARO-DUX4 for Injection
Drug: ARO-DUX4 for Injection
single or multiple doses of ARO-DUX4 by intravenous (IV) infusion
Placebo Comparator: Placebo
(0.9%NaCl)
Drug: Placebo
calculated volume to match active treatment by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
Time Frame: Single dose phase: Up to Day 90; multiple dose phase: Up to Day 360
Single dose phase: Up to Day 90; multiple dose phase: Up to Day 360

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time from Zero to Infinity (
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
AUCinf)
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Terminal Elimination Half-Life (t1/2)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Systemic Clearance (CL)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Volume of Distribution (Vss)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Fraction of Drug Excreted in Urine as Percent of Intravenous (IV) Dose (Fe)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
PK of ARO-DUX4: Renal Clearance (CLr)
Time Frame: Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose
Single dose phase: through 48 hours post-dose, Multiple dose phase: through 24 hours post first and second dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arrowhead Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2024

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

November 8, 2023

First Submitted That Met QC Criteria

November 13, 2023

First Posted (Actual)

November 15, 2023

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARODUX4-1001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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