FHND1002 for ALS Treatment: Phase 2

NCT07138014 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: FHND1002-II-01
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase II clinical trial evaluating the effectiveness and safety of an investigational drug, FHND1002 granules, in adults with Amyotrophic Lateral Sclerosis (ALS). The main goals are: To determine if FHND1002 can slow the progression of ALS compared to a placebo. To assess the safety and tolerability of two different doses of FHND1002 (100mg and 200mg) in ALS patients. Approximately 180 participants will be randomly assigned (like flipping a coin) to one of three groups: FHND1002 100mg once daily FHND1002 200mg once daily Placebo (an inactive substance) once daily Assignment will consider disease severity (ALSFRS-R score) and where symptoms started (Limb vs. Bulbar). Participants can continue taking stable doses of approved ALS medications (like riluzole or edaravone) or be on no medication. The study consists of: A Screening Period (up to 4 weeks). A Double-Blind Treatment Period (48 weeks). During the 48-week treatment period: Participants will take their assigned granules orally once daily (with or without food). They will attend clinic visits at Weeks 2, 4, 12, 24, 36, and 48 for safety checks. Effectiveness will be measured at Weeks 12, 24, 36, and 48 using standard ALS assessments, including the ALS Functional Rating Scale-Revised (ALSFRS-R), breathing tests (FVC%), and quality of life/questionnaires (ROADS, ALSAQ-5).

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Amyotrophic Lateral Sclerosis (ALS); Phase II; FHND1002

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at Week 48

  The difference in least-squares mean (LSMean) change from baseline to Week 48 in ALSFRS-R total score between FHND1002 treatment groups (combined or individual doses) and placebo. Missing data due to early discontinuation will be handled using multiple imputation based on observed data from the same treatment group. Analysis will use a repeated measures mixed-effects model (MMRM) adjusted for baseline ALSFRS-R score, site of onset (limb vs. bulbar), treatment group, visit, and treatment-by-visit interaction, with subject as a random effect.

  Baseline to Week 48

Study Arms (3)

FHND1002 100mg

EXPERIMENTAL

Participants receive FHND1002 granules 100mg orally once daily for 48 weeks. Administration may occur fasting or with food. Concurrent stable ALS medications (e.g., edaravone/riluzole) are permitted if maintained ≥4 weeks prior to enrollment and unchanged during the study. Standard ALS care continues throughout.

Drug: FHND1002 100mg

FHND1002 200mg

EXPERIMENTAL

Participants receive FHND1002 granules 200mg orally once daily for 48 weeks. Administration may occur fasting or with food. Pre-existing stable ALS therapies (edaravone/riluzole) are allowed if dose-stable for ≥4 weeks pre-randomization and maintained during the trial. Standard supportive care is provided.

Drug: FHND1002 200mg

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo granules orally once daily for 48 weeks. Administration conditions (fasting/with food) mirror active arms. Background ALS medications (edaravone/riluzole) are permitted if stabilized ≥4 weeks before enrollment and unchanged throughout the study. Standard ALS management continues.

Drug: Placebo

Interventions

FHND1002 100mg DRUG

Investigational oral granules containing 100mg FHND1002 (chemical entity: 3-n-butylphthalide derivative). Administered once daily for 48 weeks. Granules are packaged in unit-dose sachets with identical appearance across all study arms. Participants dissolve contents in water prior to ingestion. Stability testing confirms compatibility with fasting or fed conditions.

FHND1002 100mg

FHND1002 200mg DRUG

Investigational oral granules containing 200mg FHND1002 (3-n-butylphthalide derivative). Delivered as two 100mg sachets or one 200mg sachet to maintain blinding. Daily dosing regimen for 48 weeks. Granule composition matches 100mg formulation in excipients and organoleptic properties.

FHND1002 200mg

Placebo DRUG

Placebo granules identical to active intervention in appearance, taste, packaging, and administration method. Contains inert excipients (microcrystalline cellulose, lactose monohydrate) without active

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be ≥18 years of age at the time of signing the informed consent form.
• Subjects must have a diagnosis of Amyotrophic Lateral Sclerosis (ALS) meeting the revised El Escorial World Federation of Neurology criteria categories including Clinically Definite ALS, Clinically Probable ALS, Laboratory-supported Probable ALS, or Clinically Possible ALS.
• Subjects must demonstrate a documented mean monthly decline of ≥0.5 points in the ALS Functional Rating Scale-Revised (ALSFRS-R) score since initial diagnosis.
• Disease duration must be ≤2 years calculated from the onset of the first ALS-related symptom.
• At screening, subjects must have an ALSFRS-R total score ≥30 with a swallowing function subscore ≥2 and all respiratory-related subscores at 4 points.
• Subjects must have a Body Mass Index (BMI) ≥18.5 kg/m².
• Subjects may or may not be receiving stable therapeutic doses of approved ALS medications (e.g., edaravone, riluzole) prior to enrollment, provided any existing regimen remains unchanged throughout the study.
• Subjects must demonstrate ability to understand study procedures, willingness to comply, voluntary participation, and provide signed informed consent.

You may not qualify if:

• Subjects with coexisting neurological disorders that may mimic ALS symptoms or interfere with efficacy assessment (e.g., cervical/lumbar spondylosis, dementia, history of seizures except childhood febrile seizures) will be excluded.
• Subjects exhibiting motor conduction block or sensory nerve conduction abnormalities on electromyography (EMG) testing will be excluded.
• Subjects with any history of spinal surgery within 3 months prior to screening will be excluded.
• Subjects showing clinically significant laboratory abnormalities at screening including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 × upper limit of normal (ULN), or serum creatinine (Scr) \> ULN will be excluded.
• Subjects with severe/uncontrolled cardiac, hepatic, renal, hematologic, or neoplastic diseases, or active severe psychiatric disorders will be excluded.
• Subjects with known or suspected hypersensitivity to FHND1002 or its excipients will be excluded.
• Subjects who have participated in another investigational drug/device trial within 1 month prior to screening will be excluded.
• Subjects deemed by the Investigator to have any condition compromising safety, data integrity, or study compliance will be excluded.

Sponsors & Collaborators

• Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd.: lead

Related Publications (8)

• Todd TW, Petrucelli L. Modelling amyotrophic lateral sclerosis in rodents. Nat Rev Neurosci. 2022 Apr;23(4):231-251. doi: 10.1038/s41583-022-00564-x. Epub 2022 Mar 8.

  PMID: 35260846 BACKGROUND

• Fang MY, Markmiller S, Vu AQ, Javaherian A, Dowdle WE, Jolivet P, Bushway PJ, Castello NA, Baral A, Chan MY, Linsley JW, Linsley D, Mercola M, Finkbeiner S, Lecuyer E, Lewcock JW, Yeo GW. Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD. Neuron. 2019 Sep 4;103(5):802-819.e11. doi: 10.1016/j.neuron.2019.05.048. Epub 2019 Jul 1.

  PMID: 31272829 BACKGROUND

• Piol D, Robberechts T, Da Cruz S. Lost in local translation: TDP-43 and FUS in axonal/neuromuscular junction maintenance and dysregulation in amyotrophic lateral sclerosis. Neuron. 2023 May 3;111(9):1355-1380. doi: 10.1016/j.neuron.2023.02.028. Epub 2023 Mar 23.

  PMID: 36963381 BACKGROUND

• Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, Balka KR, Calleja DJ, Moghaddas F, Ni E, McLean CA, Samson AL, Tyebji S, Tonkin CJ, Bye CR, Turner BJ, Pepin G, Gantier MP, Rogers KL, McArthur K, Crouch PJ, Masters SL. TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell. 2020 Oct 29;183(3):636-649.e18. doi: 10.1016/j.cell.2020.09.020. Epub 2020 Oct 7.

  PMID: 33031745 BACKGROUND

• Baughn MW, Melamed Z, Lopez-Erauskin J, Beccari MS, Ling K, Zuberi A, Presa M, Gonzalo-Gil E, Maimon R, Vazquez-Sanchez S, Chaturvedi S, Bravo-Hernandez M, Taupin V, Moore S, Artates JW, Acks E, Ndayambaje IS, Agra de Almeida Quadros AR, Jafar-Nejad P, Rigo F, Bennett CF, Lutz C, Lagier-Tourenne C, Cleveland DW. Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science. 2023 Mar 17;379(6637):1140-1149. doi: 10.1126/science.abq5622. Epub 2023 Mar 16.

  PMID: 36927019 BACKGROUND

• Mead RJ, Shan N, Reiser HJ, Marshall F, Shaw PJ. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nat Rev Drug Discov. 2023 Mar;22(3):185-212. doi: 10.1038/s41573-022-00612-2. Epub 2022 Dec 21.

  PMID: 36543887 BACKGROUND

• Watanabe H, Atsuta N, Hirakawa A, Nakamura R, Nakatochi M, Ishigaki S, Iida A, Ikegawa S, Kubo M, Yokoi D, Watanabe H, Ito M, Katsuno M, Izumi Y, Morita M, Kanai K, Taniguchi A, Aiba I, Abe K, Mizoguchi K, Oda M, Kano O, Okamoto K, Kuwabara S, Hasegawa K, Imai T, Kawata A, Aoki M, Tsuji S, Nakashima K, Kaji R, Sobue G. A rapid functional decline type of amyotrophic lateral sclerosis is linked to low expression of TTN. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):851-8. doi: 10.1136/jnnp-2015-311541. Epub 2016 Jan 8.

  PMID: 26746183 BACKGROUND

• Xu L, Liu T, Liu L, Yao X, Chen L, Fan D, Zhan S, Wang S. Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol. 2020 Apr;267(4):944-953. doi: 10.1007/s00415-019-09652-y. Epub 2019 Dec 3.

  PMID: 31797084 BACKGROUND

Related Links

• Description the protocol of the study

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Dongsheng Fan, MD, PhD, Professor

CONTACT

010-82265159; dsfan@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomized in a 1:1:1 ratio to three parallel arms: * Arm 1: FHND1002 100mg granules + standard ALS care * Arm 2: FHND1002 200mg granules + standard ALS care * Arm 3: Matching placebo granules + standard ALS care Stratification factors: 1) Baseline ALSFRS-R (≥40 vs \<40); 2) Site of onset (limb vs bulbar). Double-blind treatment period: 48 weeks.

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 22, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share