A Phase II, Open-label Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy in Males With Classic Fabry Disease Who Have Never Received Any Treatment

AceLink Therapeutics, Inc.6 sites in 1 country16 target enrollmentOctober 25, 2023

ConditionsFabry Disease

InterventionsAL01211

Overview

Phase: Phase 2
Intervention: AL01211
Conditions: Fabry Disease
Sponsor: AceLink Therapeutics, Inc.
Enrollment: 16
Locations: 6
Primary Endpoint: Treatment-emergent adverse events (TEAEs)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase II, open-label study designed to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of AL01211 in male subjects with classic Fabry disease who have never received any treatment (eg. ERT or chaperone therapy). Eligible subjects will receive 182 days (26 weeks) of study treatment as the primary study period followed by an extension period. The total study duration for a subject is up to at most 2 years including the primary period of 26 weeks.

Registry

clinicaltrials.gov

Start Date

October 25, 2023

End Date

June 2026

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

Male

Investigators

Sponsor

AceLink Therapeutics, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male subjects with classic Fabry mutations with between 18 and 60 years of age, inclusive, at screening.
•Have never received any Fabry disease-specific treatment (eg. ERT, chaperone therapy).
•Signed and dated informed consent prior to any study mandated procedure.
•Confirmed diagnosis of Fabry disease as documented by the presence of a Fabry genetic variant of known significance and documented (within 10 years prior to study entry) leukocyte αGAL activity of \<4 nmol/hr/mg or plasma αGAL activity of \<1.5 nmol/hr/mL. If the genetic variant is not known or available, genetic test will be done to document the genetic variation after obtaining the patient's informed consent. If documented leukocyte or plasma αGAL activity is unavailable, the subject must consent to plasma αGAL activity screening.
•eGFR ≥50 mL/min/1.73 m2 by CKD-EPI Creatinine-Cystatin Equation (2021) at the screening visit.
•Subject agrees to comply with all procedural requirements as presented in the protocol, including participation in observational period which extends beyond the planned 52-week treatment duration of the study and 1 month follow-up visit.
•For subjects receiving renin-angiotensin-aldosterone system (RAAS) inhibitors/blockers (ACEIs, ARBs, aldosterone receptor antagonists) or sodium-glucose cotransporter-2 (SGLT2) inhibitors, the dose should be stable (ie, prescribed dose and frequency) for at least the immediate 3 months prior to screening.
•Symptom or clinical finding of ≥1 of the characteristic features of Fabry disease, such as, but not limited to, neuropathic pain, symptoms of gastrointestinal, renal, or cardiac dysfunction.
•Willing to undergo opthalmological examination with photodocumentation at baseline and at specified times during the study.
•Plasma Lyso GL3 ≥25 ng/mL.

Exclusion Criteria

•Subject on regular dialysis for the treatment of chronic kidney disease or has undergone a kidney transplant.
•Clinically significant abnormal liver function judged by the investigator, including but not limited to serum total bilirubin \> 1.5 the upper limit of normal \[ULN\], serum alanine aminotransferase \> 2 times the ULN, or aspartate aminotransferase \>2 times the ULN).
•Scheduled in-patient hospitalization, including elective surgery, during the study.
•A positive result on any of the following tests: hepatitis B surface antigen (HBsAg) (If HBsAg is positive, hepatitis B virus DNA needs to be tested, and the copy number \>ULN), antihepatitis C virus antibodies, anti-human immunodeficiency virus 1 and 2 antibodies.
•A cortical cataract (COR) \>one quarter of the lens circumference (Grade COR-2) or a posterior subcapsular cataract (PSC) with about 30% opacity (Grade PSC-2), according to World Health Organization grading. Subjects with nuclear cataracts are not excluded.
•Currently receiving, or has received within the past month, potentially cataractogenic medications, including a chronic regimen (more frequently than once every 2 weeks) of any route of corticosteroids (limited to medium and high-potency topical steroids; intranasal steroids are acceptable) or any medication that may cause cataracts (such as phenothiazines and miotics, amiodarone, allopurinol and phenytoin) according to the Prescribing Information.
•Male subjects with partners of child-bearing potential who do not agree to use a medically accepted, highly eﬀective method of contraception during the study until 3 months after the last administration of study drug. Male subjects must be willing to withhold from any sperm donation during the study and up to 3 months after the last dose of study treatment.
•Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the investigator, would interfere with the subject's compliance with the requirements of the study or interpretation of the results.
•Prior participation in a study involving an investigational drug within 90 days since the end of the study or within 5 half lives since the last dose of investigational drug, whichever is longer.
•Unwilling to comply with the requirements of the protocol.

Arms & Interventions

AL01211 60 mg, once daily

After enrolling into 30 mg arm is completed and preliminary data show good safety, 9 subjects will be enrolled in this arm, receiving 60 mg AL01211 treatment, once daily

Intervention: AL01211

AL01211 30 mg, once daily

9 subjects will first be enrolled in this arm, receiving 30 mg AL01211 treatment, once daily

Intervention: AL01211

Outcomes

Primary Outcomes

Treatment-emergent adverse events (TEAEs)

Time Frame: 104 weeks

Number of subjects with TEAEs will be evaluated. AEs will be coded by using the current version of the Medical Dictionary for Regulatory Activities and summarized by system organ class, preferred term, and dose level for the number and percent of AEs reported, the number of subjects reporting each AE, and the number of subjects with any AE.

Secondary Outcomes

The pharmacodynamics of AL01211 by measuring plasma GL1 level(Baseline, weeks 2, 4, 8, 13, 26, 52, 104)
The pharmacodynamics of AL01211 by measuring plasma lyso globotriaosylceramide (Lyso GL3) level(Baseline, weeks 2, 4, 8, 13, 26, 52, 104)
The pharmacokinetics of AL01211 in plasma(Weeks 1, 2, 4, 8, 13, 26, 52, 104)
The effect of AL01211 on renal function: eGFR(104 weeks)
The effect of AL01211 on quality of life: EQ-5D-5L(104 weeks)
The effect of AL01211 on patient reported global impression of severity of disease(104 weeks)
The pharmacodynamics of AL01211 by measuring urine lyso globotriaosylceramide (Lyso GL3) level(Baseline, weeks 4, 13, 26, 52, 104)
The pharmacokinetics of AL01211 in urine(weeks 1 and 13)
The effect of AL01211 on symptoms of neuropathic pain: weekly frequency of use of pain medication(104 weeks)
The pharmacodynamics of AL01211 by measuring plasma GL3 level(Baseline, weeks 2, 4, 8, 13, 26, 52, 104)
The pharmacodynamics of AL01211 by measuring urine GL3 level(Baseline, weeks 4, 13, 26, 52, 104)
The effect of AL01211 on renal function: UACR(104 weeks)
The pharmacodynamics of AL01211 by measuring GL3 inclusion in kidney biopsies(Baseline, weeks 52, and 104)
The effect of AL01211 on renal function: UPCR(104 weeks)
The effect of AL01211 on cardiac function: MRI±gadolinium(104 weeks)
The effect of AL01211 on cardiac function: troponin T(104 weeks)
The effect of AL01211 on symptoms of neuropathic pain: average weekly pain severity during Fabry crises(104 weeks)
The effect of AL01211 on symptoms of neuropathic pain: weekly frequency of Fabry crises(104 weeks)
The effect of AL01211 on clinician reported global impression of change of disease(104 weeks)
The effect of AL01211 on symptoms of neuropathic pain: BPI-SF(104 weeks)
The effect of AL01211 on symptoms of gastrointestinal disturbance(104 weeks)
The effect of AL01211 on overall disease burden(104 weeks)
The effect of AL01211 on clinician reported global impression of severity of disease(104 weeks)
The effect of AL01211 on patient reported global impression of change of disease(104 weeks)