ARISE-HF
Research type
Research Study
Full title
Aldose Reductase Inhibition for Stabilization of Exercise capacity in Heart Failure (ARISE-HF: A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients with Diabetic Cardiomyopathy / Stage B Heart Failure at High Risk of Progression to Overt Heart Failure (Stage C Heart Failure)
IRAS ID
270378
Contact name
Minal Kara
Contact email
Sponsor organisation
Applied Therapeutics Inc
Eudract number
2019-002558-21
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
136043, IND
Duration of Study in the UK
3 years, 8 months, 3 days
Research summary
Summary of Research
Diabetic cardiomyopathy (DbCM) is a type of heart disease that may progress to heart failure, a serious medical condition that can be debilitating and fatal if left untreated.The purpose of this study is to learn about the effects of the research medicine AT-001, to find the best dose, and to see how safe AT-001 is, compared to a placebo. A placebo looks like the research medicine but does not contain any medication (active ingredient).
The study consists of 2 parts. Part A (screening through to month 27)and Part B (extension of at least 12 months after completion of Part A). Participants will begin the study in Part A and then enter Part B.
Part A: will evaluate the safety and efficacy of two doses of AT-001 twice a day compared to placebo.
Part B: will continue to evaluate the safety and efficacy of AT-001 compared to placebo for a minimum of 12 months after completion of part A.This is a randomised, placebo-controlled, double blind study meaning neither the participant nor the study doctor will know which medication is being given.
Applied Therapeutics Inc is sponsoring this multicentre study and it is anticipated that approximately 675 participants will be randomised to AT-001 or placebo in a 1:1:1 ratio across the world.
Summary of Results
Name of Sponsor: Applied Therapeutics, Inc.
Name of Finished Product: AT-001
Name of Active Ingredient: AT-001
Title of Study: Aldose Reductase Inhibition for Stabilization of Exercise capacity in Heart Failure (ARISE-HF): A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients with Diabetic Cardiomyopathy / Stage B Heart Failure at High Risk of Progression to Overt Heart Failure (Stage C Heart Failure) Study Centers: 79 centers in the United States, Canada, France, Germany, Spain, United Kingdom, Australia, Hong Kong, Czech Republic, and Poland. Sixty-four of those sites randomized patients.
Publication (reference): None
Study Period: Approximately 4 years, 19 weeks (approximately 227 weeks) Initiation Date: 18 September 2019 Completion Date: 26 January 2024 Phase of Development: 2/3
Indication: Diabetic cardiomyopathy (DbCM) Study Objectives:
Primary: The primary objective of this pivotal Phase 2/3 study was the following:
• To demonstrate that AT-001 compared with placebo decreases the worsening of performance on a cardiopulmonary exercise test (CPET) in patients with DbCM/Stage B heart failure (SBHF).
Secondary: The secondary objectives were the following:
• To evaluate the efficacy of AT-001 compared with placebo in preventing progression from SBHF to Stage C heart failure (SCHF), defined as the occurrence of 1 of the following events:
o Cardiovascular (CV) death.
o Hospitalization for heart failure (HF).
o Urgent HF visit; or
o New diagnosis of HF.
• To evaluate the effect of AT-001 compared with placebo in patients with DbCM/SBHF in decreasing the levels of the biomarker N-terminal pro-B-type natriuretic protein (NT-proBNP).
• To evaluate the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the score of the modified Kansas City Cardiomyopathy Questionnaire (mKCCQ).
• To evaluate the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the percentage of patients with any changes and clinically significant changes (>6%) in peak volume of oxygen uptake (VO2).
• To evaluate the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the significant worsening of DbCM from baseline.
• To evaluate the effect of AT-001 compared with placebo in patients with DbCM/SBHF on the changes in systolic function assessed by global longitudinal strain (GLS), left ventricular (LV) hypertrophy (LVH), left atrial enlargement (LAE), diastolic dysfunction assessed by E/E’ (ratio of mitral peak velocity of early filling [E] to early diastolic mitral annular velocity [E’]), right ventricular systolic pressure (RVSP) by echocardiography; and • To evaluate the safety of chronic administration of AT-001 to patients with DbCM/SBHF. Exploratory: The exploratory objectives were the following:
• To evaluate the effect of AT-001 compared with placebo on various biomarkers, estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR) and cardiac autonomic neuropathy (CAN) parameters, and Physical Activity Scale for the Elderly (PASE) total score; and • To evaluate the efficacy of AT-001 compared with placebo in preventing hospitalization or death due to cardiac events.
Methodology:
This was a Phase 2/3, randomized, placebo-controlled study in adult patients with DbCM/SBHF.
The study was designed to assess the efficacy of AT-001 compared with placebo in these patients and to assess the safety and tolerability of chronic administration of AT-001.
This study consisted of 2 sequential placebo-controlled parts with the same patients continuing from Part A to Part B:
• Part A: From screening through Month 27; and • Part B: Extension of at least 12 months after completion of Part A through the Study Closeout Visit or Post-Treatment Follow-up Visit, whichever occurred later. Note that Part B was not implemented in the Czech Republic nor the United Kingdom. In these countries, the last of dosing was at the time patients reached Month 27. Data collection for Month 15 represents calendar dates 15 months and 18 months after randomization Data collection for Month 27 represents calendar dates 27 months and 30 months after randomization Part A:
Part A evaluated, under double-blinded conditions, the safety and efficacy of 2 doses (1500 mg twice daily [BID] and 1000 mg BID) of AT-001 versus placebo administered for approximately 27 to 30 months to patients with DbCM/SBHF. Eligible patients were randomized 1:1:1 to AT-001 1500 mg BID, AT-001 1000 mg BID, or placebo. Randomization was stratified by geographical region (North America versus Rest of the World), by use of a sodium-glucose linked transporter-2 inhibitor (SGLT2-i) at baseline (use versus no use), by use of a glucagon-like peptide 1 receptor agonist (GLP-1RA) at baseline (use versus no use), and by the baseline respiratory exchange rate at the baseline CPET (respiratory exchange ratio [RER] 1.15 versus <1.15).
Patients recorded any adverse events (AEs), associated concomitant medications, and any missing
dose(s) of study drug and reason(s) for not taking the dose(s) in a study diary. During Part A, patients had Full On-Site Visits every 3 months for complete safety assessment (including physical exam and laboratory tests) and drug accountability/dispensation. Patients returned to the center at Months 1 and 2 for drug accountability/dispensation, as well as safety monitoring with emphasis on renal function. After the Month 3 Full On-Site Visit, if no safety issues were identified, patients received monthly phone contacts (or video-teleconference, if possible) between the Full On-Site Visits for the duration of Part A. At all visits and monthly phone contacts, the study diary was reviewed.
Patients underwent CPET during screening (baseline test, up to 6 months before randomization) and at Month 15 -. Another post-randomization CPET may have been performed at Month 27 - Patients who reached Month 27 after the Data Monitoring Committee had communicated to the Sponsor that the Month 15 CPET analysis showed a statistically significant difference in favor of at least 1 dose of AT-001 compared with placebo, did not perform the second post-baseline CPET at Month 27. A blood sample for analysis of NT-proBNP was taken at randomization (baseline) and at Months 6, 15, and 27. Blood samples for analyses of all other biomarkers were taken at randomization (baseline) and at Months 15 and 27. The mKCCQ and PASE questionnaires were administered at randomization (baseline) and at Months 15 and 27. A modified version of the Kansas City Cardiomyopathy Questionnaire, the mKCCQ, was used to take into account that the study patients did not have overt HF at baseline. An echocardiogram was conducted at screening (baseline, up to 6 months before randomization) and at Month 27. Clinical safety laboratory tests were evaluated at screening, randomization (baseline), and every Full On-Site Visit (every 3 months). Part A completed after the Month 27 visit. Upon completion of Part A, patients continued into Part B.
As previously noted, for patients in the Czech Republic and United Kingdom, the last day of dosing was at the Month 27 visit. - Patients who were still taking study drug at the time of the Month 27 visit had a Post-Treatment Follow-Up Visit approximately 30 3 days after the last dose of study drug (i.e., at the time of the Month 27 Visit).
Part B:
Part B evaluated the safety of chronic administration of AT-001 versus placebo in the same patients with DbCM/SBHF who had previously been evaluated in Part A. Both the Investigators and the study patients remained blinded to the treatment allocation. In Part B, patients continued to receive the same double-blinded treatment that they had received in Part A. Patients did not keep a study diary during Part B. If no safety issues were identified during Part A, then only serious AEs (SAEs), and AEs leading to treatment discontinuation were to be recorded during Part B. Also, only concomitant medications associated with these events were recorded. During Part B, patients had Full On-Site Visits every 6 months for complete safety assessment (including physical exam and laboratory tests) and drug accountability/dispensation. On a monthly basis in between the Full On-Site Visits, patients were contacted by phone (or video teleconferences, if possible). The study was planned to be terminated 39 months after the last patient in, i.e., last patient randomized in the study. At this time point, all randomized patients (regardless of compliance with study drug or study procedures), attended the Study Closeout Visit, with the exception of patients lost to follow-up or who had prematurely discontinued study participation and had stated that they did not want to be contacted in the future at any time during the study up to and including the timing of the Study Closeout Visit. The Study Closeout Visit included a complete safety assessment (including physical exam and laboratory tests) and drug accountability (when appropriate). Patients who were taking study drug at the time of the Study Closeout Visit had a Post-Treatment Follow-up Visit approximately 30 (±3) days after the last dose of study drug (i.e., at the time of the Study Closeout Visit).
Substudies:
The study also included 2 substudies requiring additional study procedures. Each sub study was conducted only in the subset of patients who specifically consented to the sub study in writing. In the neuropathy sub study, patients had the following assessments done at randomization (baseline), Month 27, and at Month 39:
1. The Neuropathy Total Symptom Score-6 (NTSS-6); and 2. The modified Toronto Clinical Neuropathy Scale (mTCNS).
In the retinopathy sub study, patients had the following assessments done at screening, Month 27, and at Month 39:
1. Color Fundus Photography; and
2. Optical Coherence Tomography, if available.
Duration of Treatment: Approximately 39 months after the last patient in (including Parts A and B) Number of Patients:
Planned: 675 patients
Screened: 2107 patients
Randomized: 691 patients
Completed: 443 patients
Discontinued: 248 patients
Diagnosis and Main Criteria for Inclusion: All patients enrolled in this study had a diagnosis of type 2 diabetes mellitus. Patients were either aged 60 years or aged 40 to <60 years with at least 1 of the following risk factors: duration of diabetes 10 years or eGFR <60 mL/minute/1.73 m2.
Investigational Product and Comparator Information:
Patients were randomly assigned in a 1:1:1 ratio to AT-001 (1500 mg BID), AT-001 (1000 mg BID), or matching placebo. AT-001 drug product was provided as AT-001 powder in a 500 mg strength capsule, packaged in blister cards.
At the conclusion of the study, any unused study drug was returned to the Sponsor or destroyed by the study center pursuant to written authorization by the Sponsor and applicable regional/local regulations.
Criteria for Evaluation:
Efficacy:
The primary efficacy endpoint of this study was the following:
• Changes in CPET performance (peak VO2) from baseline to Month 15 The secondary efficacy endpoints of this study were the following:
• Changes in CPET performance (peak VO2) from baseline to last observation at the time of primary endpoint analysis. Last observed CPET was 15 months for most patients or was 27 months for patients who completed a Month 27 CPET test.
• Change in the total score for the PASE from baseline to Month 15.
• Change in the mKCCQ score from baseline to Month 15.
• Change in the levels of NT-proBNP from baseline to Month 15; and • Percentage of patients with significant worsening of DbCM from baseline to Month 15 and Month 27, defined as either: 1) a 40% increase in NT-proBNP or 2) a 40% increase in high-sensitivity troponin T (HsTnT) or 3) a 5-point decrease in the mKCCQ score or 4) a 20-point decrease in the PASE score. The other secondary efficacy endpoints of this study were the following:
• Change in CPET performance (peak VO2) from baseline to Month 15 in patients with a peak VO2 >15 mL/kg/minute at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 in patients with a peak VO2 15 mL/kg/minute at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 in patients with a RER 1.15 at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 in patients with RER <1.15 at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 with an NT-proBNP of >125 ng/mL at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 with an NT-proBNP of 125 ng/mL at baseline; Change in CPET performance (peak VO2) from baseline to Month 15 with an HsTnT of >14 ng/L at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 with an HsTnT of 14 ng/L at baseline; • Change in CPET performance (peak VO2) from baseline to Month 15 in patients not treated with SGLT2-i or GLP-1RA; • Change in CPET performance (peak VO2) from baseline to Month 15 in patients treated with SGLT2-i or GLP-1RA; • Change in the score of the mKCCQ from baseline to Month 15, in patients with a peak VO2 of >15 mL/kg/minute at baseline; • Change in the score of the mKCCQ from baseline to Month 15, in patients with a peak VO2 of 15 mL/kg/minute at baseline; • Change in the score of the mKCCQ from baseline to Month 15, in patients with an NT-proBNP of >125 ng/mL at baseline; • Change in the score of mKCCQ from baseline to Month 15 in patients with an NT-proBNP of 125 ng/mL at baseline; • Clinically significant decrease in peak VO2 (i.e., >6%) from baseline to Month 15; • Percentage of patients with the following changes in peak VO2 from baseline to Month 15:
o Any decrease (overall population);
o Any decrease (excluding patients with a peak VO2 15 mL/kg/minute at baseline); o Any decrease (excluding patients with a peak VO2 >15 mL/kg/minute at baseline); o Any decrease (excluding SGLT2-i and GLP-1RA users at any time); o Any decrease (excluding patients with an NT-proBNP 125 ng/mL at baseline); o Any decrease (excluding patients with an NT-proBNP >125 ng/mL at baseline); o Any increase (overall population); o Any increase (excluding patients with a peak VO2 15 mL/kg/minute at baseline); o Any increase (excluding patients with a peak VO2 >15 mL/kg/minute at baseline); o Any increase (excluding SGLT2-i and GLP-1RA users at any time); o Any increase (excluding patients with an NT-proBNP at baseline 125 ng/mL at baseline); o Any increase (excluding patients with an NT-proBNP at baseline >125 ng/mL at baseline); o Clinically significant increase (i.e., >6%) (overall population); o Clinically significant increase (i.e., >6%) (excluding patients with a peak VO2 15 mL/kg/minute at baseline); o Clinically significant increase (i.e., >6%) (excluding patients with a peak VO2 >15 mL/kg/minute at baseline); o Clinically significant increase (i.e., >6%) (excluding SGLT2-i and GLP-1RA users at any time); o Clinically significant increase (i.e., >6%) (excluding patients with an NT-proBNP at baseline 125 ng/mL at baseline); and o Clinically significant increase (i.e., >6%) (excluding patients with an NT-proBNP at baseline >125 ng/mL at baseline).
• Rate of progression of SBHF to SCHF defined by the occurrence of 1 of the following events:
o CV death;
o Hospitalization for HF;
o Urgent HF visit;
o New diagnosis of HF.
The exploratory endpoints of this study were the following:
• Changes in eGFR from baseline to last observed visit; • Changes in UACR from baseline to last observed visit; • Changes in CAN parameters (resting heart rate and blood pressure response to standing) from baseline to Post-Treatment Follow-up Visit; • Changes from baseline for biomarkers potentially involved in the pathophysiology of CV, renal, and metabolic diseases. These include sorbitol, HsTnT, soluble suppression of tumorigenicity-2, reactive oxygen species, growth differentiation factor 15, nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin (IL)-1, IL-6, high-sensitivity C-reactive protein, intercellular adhesion molecule-1, E-selectin, TRAIL receptor 2, and markers of fibrosis, including but not limited to propeptide of type VI collagen (PRO-C6) and titin degradation molecule (TIM). Other biomarkers may have been decided subsequently, depending on the state of knowledge at the time of the analysis. Blood samples were collected and archived for future analysis after study termination; • To evaluate the effect of AT-001 compared with placebo in patients with DbCM on the changes in GLS, LVH, LAE, diastolic dysfunction, and RVSP by echocardiography from baseline to Month 27; and • Percentage of patients with death or hospitalization due to a cardiac event through the last observed visit.
All deaths and hospitalizations were independently adjudicated by the Cardiovascular Endpoint Committee (CEC). Therefore, the exploratory analysis of the percentage of patients with hospitalization or death due to a cardiac event through the Study Closeout Visit included the following events by treatment group:
o Deaths adjudicated as CV death by the CEC. These included sudden deaths and deaths of undetermined cause; and o Hospitalizations adjudicated as hospitalizations due to a cardiac event by the CEC.The study also included a Neuropathy Sub study and a Retinopathy Sub study. The substudies were only conducted in the subset of patients who provided specific written consent for the sub study. Endpoints in the substudies were the following:
• Diabetic Neuropathy Sub study:
o Change in the mTCNS score from baseline to last observation (Month 15 or 27) for patients with a score 5, at baseline; o Change in the mTCNS score from baseline to last observation (Month 15 or 27) for all patients who were evaluated at baseline; o Change in the NTSS-6 from baseline to last observation (Month 15 or 27) for patients with >2 symptoms reported at baseline; and o Change in the NTSS-6 from baseline to last observation (Month 15 or 27) for all patients who were evaluated at baseline.
• Diabetic Retinopathy Sub study:
o Proportion of patients with a change in diabetic retinopathy stage (mild non-proliferative diabetic retinopathy [NPDR], to moderate NPDR, to severe NPDR, to proliferative diabetic retinopathy) at Month 27.
Safety:
Safety was assessed by the following:
• All treatment-emergent AEs (TEAEs);
• SAEs and AEs leading to study drug discontinuation; • Safety laboratory tests (clinical chemistry, hematology, and urinalysis):
o Increase in alanine aminotransferase or aspartate aminotransferase >3 upper limit of normal must have been monitored as described in Appendix D of the Clinical Study Protocol; o Changes in eGFR (<30 mL/minute/1.73 m2 or decrease of >30% of baseline) must have been monitored as described in Appendix E of the Clinical Study Protocol; and o Significant changes in the kidney stone risk panel evaluated in the 24-hour urine collections must have been monitored as described in Appendix E of the Clinical Study Protocol.
• Vital signs;
• Physical examinations; and
• 12-lead electrocardiograms
Statistical Methods:
The analysis was performed according to the following population definitions:
Efficacy Analysis Sets: Following the Intent-To-Treat (ITT) principle, all efficacy analyses were based on the treatment group allocated according to the randomization schedule, irrespective of the treatment actually received.
Full Analysis Set (FAS) The primary efficacy population was the Full Analysis set (FAS) that included all randomized patients regardless of compliance with the study procedures or Investigational Study Treatment.
Per-Protocol Set (PPS) The Per-Protocol set (PPS) included all randomized patients without major protocol deviations. A list of major protocol deviations was pre-specified and finalized before database lock in an appropriate study document. Major protocol deviations included, but not limited to, the Patients who have not received at least one dose of the Investigational Study Treatment allocated in accordance with the randomization schedule Safety Set (SS): The Safety set (SS) consisted of all patients who have been randomized and have received at least one dose of study drug. Patients were reported under the actual treatment group received during the study
Efficacy:
The primary endpoint of change from baseline in peak VO2 in patients with DbCM/SBHF was analyzed at Month 15. The change in peak VO2 from baseline to Month 15 was analyzed using an ANCOVA model with treatment group (only high-dose and placebo group levels were included in the primary efficacy analysis) as a factor, and randomization stratification factors (i.e., region, use of SGLT2-i at baseline, use of GLP-1RA at baseline, and baseline RER) and baseline peak VO2 as covariates. In order not to exclude patients with missing baseline stratification factor data in the statistical model, if there were missing data for the randomization stratification factors, then the patient’s value was set to the most common category (i.e., single value imputation). The primary analysis was on the Full Analysis Set, using only the data from high-dose and placebo groups. In addition, the analysis for this endpoint was repeated on the Per-Protocol Set as a supplemental analysis.
Subgroup analyses for the primary efficacy outcome were performed by assessing the significance of the 2-way interaction term between subgroup and treatment. A covariate representing the subgroup was included in the statistical model. The main objective of subgroup analysis was to evaluate treatment effect within levels of the subgroup.
The analysis of secondary endpoints was performed without any adjustment for multiple testing. So, all treatment group comparisons for the secondary endpoints were reported and interpreted using a 2-sided α=5%. The main analysis of the secondary endpoints was based on the Full Analysis Set, including only high-dose and placebo group levels in the analysis model. In addition, all analyses for secondary endpoints were also repeated on the Per-Protocol Set as supplemental analyses. For all secondary efficacy endpoint analyses, except for the additional analysis of the primary endpoint (as described below), the main analysis was performed only including the high-dose and placebo group data (i.e., excluding the low-dose group data). An additional analysis similar to the main analysis was performed including the low-dose group data, with the comparisons of combined active doses versus placebo, and low-dose versus placebo assessed. The primary analysis model was repeated with the last available observed change from baseline in peak VO2. Each patient had 1 observation for the change from baseline to the latest available result at Month 15 or Month 27. The CPET evaluation that occurred for patients who were off treatment for 30 days or more prior to Month 27 was excluded from the analysis. All aspects of the model and analysis remained the same as the primary analysis model described above.
Safety:
Safety summary findings are presented with descriptive statistics for each treatment group. Continuous variables are generally summarized using descriptive statistics that include number of available observations, mean, median, lower quartile, upper quartile, minimum, maximum, and standard deviation. Categorical or qualitative variables are summarized using descriptive statistics that include frequency counts and percentages. All safety analyses were performed on the Safety Set.
Summary of Results:
Efficacy: For the primary efficacy endpoint of stabilization or improvement in cardiac functional capacity as measured by Peak VO2, the placebo-treated group declined by a mean (LS mean) of 0.31 ml/kg/min over 15 months of treatment, while the AT-001 1500 mg BID remained stable over time, with a mean change (LS mean) of -0.01 ml/kg/min over 15 months. While a trend favored active treatment, (AT-001 1500 mg BID) the difference between the active and placebo-treated group (0.30 ml/kg/min) was not statistically significant (p=0.210). Changes in peak VO2 in the placebo group demonstrated a statistically significant decline (M15 vs baseline: p=0.005), while there was no decline in peak VO2 in the active group (AT-001 1500 mg BID).
The pre-specified subgroup analysis excluding patients treated with an SGLT2-I or a GLP-1RA demonstrated a statistically significant difference favoring the high-dose AT-001 treated cohort vs placebo (p=0.04). The population of non-users of an SGLT-2 or a GLP-1RA accounted for 61.9 of the patients enrolled in the study. In this pre-specified subgroup, the placebo group experienced a significant decline in peak VO2 (-0.54 +0.21; month 15 vs. baseline) while the high dose remained stable over time (+0.08+0.22; month 15 vs. baseline).
Evaluation of clinically meaningful changes in cardiopulmonary functional capacity were consider as equivalent to changes in peak VO2 ≥6%2 A ≥6% decline in peak VO2 was observed in 41.8% of placebo-treated patients and 36.2% of those treated with high dose AT-001 (OR=0.80, 95% CI=0.52, 1.21; P =.29). Among non-users of SGLT2 inhibitors or GLP-1RA: 46.0% versus 32.7% (OR=0.56; 95% CI=0.33, 0.96; P =.035)
Safety: Adverse events (AEs) occurred with a similar incidence between treatment group, with proximately ~80% of patients in each treatment cohort experiencing at least 1 AE.
There was no difference in the severity of AEs between treatment groups.
In the overall study population, patients with any treatment-emergent adverse event (TEAE) related to the study drug accounted for 28.6% of the population; There were 20.4 % of patients in the placebo group vs 34.6 % in the AT-001 1500 mg group who experienced TEAE The most frequent TEAE were gastrointestinal disorders.
No individual AE was considered to be related to the active drug.
Conclusions:
Treatment with AT-001 was generally safe and well tolerated. Patients exposed to high dose AT-001 experienced a stabilization of functional capacity as measure by changes in peak VO2. Conversely, patients exposed to placebo experienced a significant decline of their functional capacity at the time of the month 15 assessment. The pre-specified primary analysis comparing AT-001 to placebo did not reach a statistically significant difference in change of function capacity by month 15, despite the strong trend favoring AT-001.
For the pre- specified subgroup of patients with no history of use of SGLT2s or GLP-1RA (accounting for most of the study population) there was a statistically significant difference in peak VO2 favoring AT-001 high dose.
Date of the Report: 04 October 2024REC name
West of Scotland REC 1
REC reference
19/WS/0188
Date of REC Opinion
15 Jan 2020
REC opinion
Further Information Favourable Opinion