Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia (CYGNET)

• ClinicalTrials.gov Identifier: NCT05008874
• Recruitment Status: Active, not recruiting
• First Posted: August 17, 2021
• Last Update Posted: December 13, 2022
• Sponsor: SwanBio Therapeutics, Inc.
• Information provided by (Responsible Party): SwanBio Therapeutics, Inc.

Study Description

Brief Summary:

The course of AMN-related disabilities over time is poorly or incompletely understood due to a limited number of patients and lack of treatments. This study will help obtain a better understanding of the progression of disease with AMN and facilitate efficient clinical development of future interventional medications.

Condition or disease	Intervention/treatment
AMN; AMN Gene Mutation; X-ALD	Other: Natural History Observation

Detailed Description:

Progressive weakness and spasticity of the legs are characteristics of numerous disorders and conditions, including those that are inherited neurological disorders.

Adrenomyeloneuropathy (AMN) is an example of an inherited form of spastic paraplegia.

Adrenoleukodystrophy (ALD) is a progressive neurodegenerative disorder caused by a mutation in the ABCD1 gene localized to the X-chromosome (Xq28). The ABCD1 gene encodes a peroxisomal adenosine triphosphate (ATP) binding cassette transporter responsible for transport of very long chain fatty acids (VLCFA) from the cytosol into the peroxisome for degradation. A mutation in ABCD1 results in reduction in the degradation of the VLCFA by peroxisomal β-oxidation, and saturated VLCFA, in particular C26:0, accumulate in tissues and body fluids (i.e., brain, nervous system, adrenal glands). One of the key clinical symptoms during aging of ALD patients is a slowly progressive axonopathy affecting sensory ascending and motor descending spinal cord tracts with 100% penetrance in men, an ALD phenotype known as AMN. There are no treatment options available, which leaves AMN patients with a progressive disorder that leads to lifelong physical disability. The progressive dying-back axonopathy represents the core clinical feature of AMN, with onset usually between 20 and 30 years of age in male participants. The initial symptoms include progressive stiffness and weakness of the legs, impaired vibration and position senses in the lower limbs, falls, sphincter disturbances and impotence, as well as scarce scalp hair (alopecia). About 66% of male AMN patients have adrenocortical insufficiency (Addison disease).

The course of AMN-related disabilities over time is poorly or incompletely understood due to a limited number of patients and lack of treatments. This study will help obtain a better understanding of the progression of disease with AMN and facilitate efficient clinical development of future SwanBio interventional medications.

Study Design

• Study Type: Observational
• Actual Enrollment: 65 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Prospective, Retrospective, Multicenter, Observational Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia
• Actual Study Start Date: June 21, 2021
• Estimated Primary Completion Date: April 30, 2023
• Estimated Study Completion Date: May 1, 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
Males with AMN; Adult males with confirmed diagnosis of ALD and symptoms of AMN.	Other: Natural History Observation; Data collection on progression of disease

Outcome Measures

Primary Outcome Measures :

1. Disease progression [ Time Frame: 2 years ]
   Characterize disease progression in adults diagnosed with AMN in serial clinical evaluations of walking

Secondary Outcome Measures :

1. Change in Quality of Life [ Time Frame: 2 years ]
   Characterize the Change in multiple Quality of Life (QoL) parameters over time

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Adult males diagnosed with ALD (without cerebral disease) and symptoms of AMN who have no other major confounding comorbidities.

Criteria

Inclusion Criteria:

1. Male adults aged ≥18 years
2. Diagnosed with ALD based on elevated VLCFA assay and pedigree analysis
3. Clinical evidence of spinal cord involvement with EDSS score between 1 and 6.5

Exclusion Criteria:

1. Diagnosed with cerebral inflammatory disease or has a history of diagnosis with cerebral inflammatory disease
2. Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease (other than adrenal insufficiency) or other abnormality, which may impact the ability to participate in the study or that may potentially confound the study results
3. Participant who, in the opinion of the Investigator, has any other medical or psychological condition or social circumstances which would impair their ability to participate reliably in the assessments, or who may increase the risk to themselves or others by participating

Contacts and Locations

Locations

United States, California

Stanford Neuroscience Health Center

Stanford, California, United States, 94304

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, New York

Weill Medical College of Cornell University

New York, New York, United States, 10065

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

Germany

University of Leipzig Medical Center

Leipzig, Germany

Netherlands

Amsterdam UMC

Amsterdam, Netherlands

Sponsors and Collaborators

SwanBio Therapeutics, Inc.

More Information

• Responsible Party: SwanBio Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05008874
• Other Study ID Numbers: SBTNHX-CT901
• First Posted: August 17, 2021
• Last Update Posted: December 13, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by SwanBio Therapeutics, Inc.:

AMN; X-ALD; Natural History; Adrenoleukodystrophy; X-linked Adrenoleukodystrophy; Adrenomyeloneuropathy; Myeloneuropathy; Spastic paraplegia; Hereditary Spastic Paraplegia; HSP; ALD; ABCD1; ALDP; CALD; CCALD; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Adrenal Insufficiency

Additional relevant MeSH terms:

Muscle Spasticity; Paraplegia; Disease Progression; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Disease Attributes; Pathologic Processes; Paralysis