Back to resultsEvaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Diffuse Cutaneous Systemic Sclerosis
Primary Purpose
Diffuse Cutaneous Systemic Sclerosis
Status
Suspended
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Patients will be randomized to receive EHP-101 or Placebo
Patients will be randomized to receive EHP-101 or Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Cutaneous Systemic Sclerosis focused on measuring Scleroderma, Systemic sclerosis, EHP-101 Oral Solution, dcSSc, diffuse, pathological processes, connective tissue disease, skin disease
Eligibility Criteria
Inclusion Criteria:
- Patients male and female ≥18 years and ≤74 years at the time of consent;
- American College of Rheumatology/ European League Against Rheumatism 2013 Criteria for SSc; dcSSc (skin thickening on upper arms, upper legs, or trunk);
- Documented SSc for up to 6 years from the first non-Raynaud's phenomenon with a total mRSS of ≥15;
- No new or increased doses of immunosuppressants medications within 3 months prior to Screening;
- Effective method of contraception for participants and their partners.
Exclusion Criteria:
- Severe or unstable Systemic Sclerosis (SSc) or SSc with end-stage organ failure;
- Patient with FVC <60%;
- History of clinically significant medical condition or concurrent medical therapies that would exclude the patient, preclude participation in the clinical trial, influence response to study product, or interfere with study assessments;
- History of gastrointestinal dysmotility requiring total parenteral nutrition or hospitalization within 6 months before Visit 1;
Any one of the following values for laboratory tests at screening:
- Haemoglobin <9 g/dL;
- Neutrophils <1.0 x 10^9/L;
- Platelets <75 x 10^9/L;
- Estimated creatinine clearance <50 mL/min according to the Cockcroft-Gault equation;
- Serum transaminases >2.0 x upper normal limit;
- Total bilirubin ≥1.5 x upper limit of normal.
Sites / Locations
- Arizona Arthritis & Rheumatology Associates, P.C.
- Care Access Research - Huntington
- Pacific Arthritis Care Center
- UCLA Division of Rheumatology
- Inland Rheumatology Clinical Trials
- Yale University
- Central Florida Pulmonary Group
- Life Clinical Trials
- Novel Clinical Research Center
- Northwestern University
- University of Minnesota
- Rutgers, The State University of New Jersey
- Cleveland Clinic
- Royal Adelaide Hospital
- Royal Prince Alfred Hospital
- Footscray Hospital
- Griffith University
- Fiona Stanley Hospital
- Westmead Hospital
- Wellington Hospital
- Centro Reumatologico
- Mindful Medical Research
- University of Puerto Rico, Medical Sciences Campus
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
EHP-101 low dose once a day
EHP-101 low dose twice a day
EHP-101 high dose once a day
EHP-101 high dose twice a day
Arm Description
Outcomes
Primary Outcome Measures
Incidence and severity of Treatment Emergent Adverse Events
This safety outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatments.
Secondary Outcome Measures
Treatment effect of EHP-101 compared to placebo as measured by the American College of Rheumatology composite response index in diffuse cutaneous Systemic Sclerosis
The ACR CRISS exponential algorithm determines the predicted probability of improvement from baseline, incorporating change in modified Rodnan Skin Score (mRSS), Forced Vital Capacity (FVC) % predicted, physician and patient global assessments, and Scleroderma Health Assessment Questionnaire Disability Index (S-HAQ-DI). The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). Subjects are not considered improved (ACR CRISS score = 0) if they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction < 45%); or 4) new pulmonary artery hypertension on right heart catheterization requiring treatment.
Treatment effect of EHP-101 compared to placebo in modified Rodnan Skin Score
The mRSS consists of an evaluation of patient's skin thickness rated by clinical palpation using a 0-3 scale (0 = normal skin; 1 = mild thickness; 2 = moderate thickness; 3 = severe thickness with inability to pinch the skin into a fold for each of 17 surface anatomic areas of the body: face, anterior chest, abdomen, and, with right and left sides of the body separately evaluated, the fingers, forearms, upper arms, thighs, lower legs, dorsum of hands and feet. Individual values are summed and defined as the total skin score. Total score is 0 to 51.
Treatment effect of EHP-101 compared to placebo in forced vital capacity percent predicted
Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness . FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%
Treatment effect of EHP-101 compared to placebo in physician global assessment score
The Physician Global Assessment of disease activity will be performed using a segmented numerical version of the visual analogue scale in which the physician selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by 2 verbal descriptors, one of "no disease activity" (score of 0) and one of "worse imaginable disease activity" (score of 10), with numbers 1-9 spaced equidistance in between. The physician will select an integer to describe disease activity. The recall period is one week.
Treatment effect of EHP-101 compared to placebo in patient global assessments score
The Patient Global Assessment will be performed with a segmented numerical version of the visual analogue scale in which the subject selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by two verbal descriptors, one of "no disease activity" (score of 0) and one of "worse imaginable disease activity" (score of 10), with numbers 1-9 spaced equidistance in between. The subject will select an integer to describe disease activity. The recall period is one week.
Treatment effect of EHP-101 compared to placebo in Scleroderma Health Assessment Questionnaire - Disability Index
S-HAQ-DI includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are two or three questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The eight scores of the eight sections are summed and divided by 8. If one section is not completed by a subject, the summed score is divided by 7. As such, maximum scores can vary with a min of 0. The result is the DI, the disability index or functional disability index. The recall period is one week.
Full Information
NCT ID
NCT04166552
First Posted
November 6, 2019
Last Updated
September 16, 2023
Sponsor
Emerald Health Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04166552
Brief Title
Evaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Diffuse Cutaneous Systemic Sclerosis
Official Title
A Phase IIa, Double-Blind, Randomised, Intracohort Placebo-Controlled, Multicentre Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EHP-101 in Patients With Diffuse Cutaneous Systemic Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Suspended
Why Stopped
Sponsor ceasing all operations due to company's shut down
Study Start Date
June 11, 2020 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emerald Health Pharmaceuticals
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this trial is to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of EHP-101 in adult subjects with diffuse cutaneous Systemic Sclerosis (dcSSc).
Detailed Description
An interventional, double-blind, randomized, intracohort placebo-controlled design will be used to test safety, tolerability, pharmacokinetics, and preliminary efficacy of EHP-101 in 36 patients ≥ 18 and ≤ 74 years of age with documented dcSSc. There is a screening period of 28 days, 84 days treatment period, and 28 days follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Cutaneous Systemic Sclerosis
Keywords
Scleroderma, Systemic sclerosis, EHP-101 Oral Solution, dcSSc, diffuse, pathological processes, connective tissue disease, skin disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a dose escalation double-blind intracohort trial starting with Cohorts 1 and 2 commencing in parallel and then Cohorts 3 and 4 commencing in parallel
Masking
ParticipantInvestigator
Masking Description
Double (intracohort)
Allocation
Randomized
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
EHP-101 low dose once a day
Arm Type
Experimental
Arm Title
EHP-101 low dose twice a day
Arm Type
Experimental
Arm Title
EHP-101 high dose once a day
Arm Type
Experimental
Arm Title
EHP-101 high dose twice a day
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Patients will be randomized to receive EHP-101 or Placebo
Intervention Description
EHP-101 or placebo will be taken once a day
Intervention Type
Drug
Intervention Name(s)
Patients will be randomized to receive EHP-101 or Placebo
Intervention Description
EHP-101 or placebo will be taken twice a day
Primary Outcome Measure Information:
Title
Incidence and severity of Treatment Emergent Adverse Events
Description
This safety outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatments.
Time Frame
Day 113
Secondary Outcome Measure Information:
Title
Treatment effect of EHP-101 compared to placebo as measured by the American College of Rheumatology composite response index in diffuse cutaneous Systemic Sclerosis
Description
The ACR CRISS exponential algorithm determines the predicted probability of improvement from baseline, incorporating change in modified Rodnan Skin Score (mRSS), Forced Vital Capacity (FVC) % predicted, physician and patient global assessments, and Scleroderma Health Assessment Questionnaire Disability Index (S-HAQ-DI). The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). Subjects are not considered improved (ACR CRISS score = 0) if they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction < 45%); or 4) new pulmonary artery hypertension on right heart catheterization requiring treatment.
Time Frame
Day 85 and Day 113
Title
Treatment effect of EHP-101 compared to placebo in modified Rodnan Skin Score
Description
The mRSS consists of an evaluation of patient's skin thickness rated by clinical palpation using a 0-3 scale (0 = normal skin; 1 = mild thickness; 2 = moderate thickness; 3 = severe thickness with inability to pinch the skin into a fold for each of 17 surface anatomic areas of the body: face, anterior chest, abdomen, and, with right and left sides of the body separately evaluated, the fingers, forearms, upper arms, thighs, lower legs, dorsum of hands and feet. Individual values are summed and defined as the total skin score. Total score is 0 to 51.
Time Frame
Day 85 and Day 113
Title
Treatment effect of EHP-101 compared to placebo in forced vital capacity percent predicted
Description
Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness . FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%
Time Frame
Day 85 and Day 113
Title
Treatment effect of EHP-101 compared to placebo in physician global assessment score
Description
The Physician Global Assessment of disease activity will be performed using a segmented numerical version of the visual analogue scale in which the physician selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by 2 verbal descriptors, one of "no disease activity" (score of 0) and one of "worse imaginable disease activity" (score of 10), with numbers 1-9 spaced equidistance in between. The physician will select an integer to describe disease activity. The recall period is one week.
Time Frame
Day 85 and Day 113
Title
Treatment effect of EHP-101 compared to placebo in patient global assessments score
Description
The Patient Global Assessment will be performed with a segmented numerical version of the visual analogue scale in which the subject selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by two verbal descriptors, one of "no disease activity" (score of 0) and one of "worse imaginable disease activity" (score of 10), with numbers 1-9 spaced equidistance in between. The subject will select an integer to describe disease activity. The recall period is one week.
Time Frame
Day 85 and Day 113
Title
Treatment effect of EHP-101 compared to placebo in Scleroderma Health Assessment Questionnaire - Disability Index
Description
S-HAQ-DI includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are two or three questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The eight scores of the eight sections are summed and divided by 8. If one section is not completed by a subject, the summed score is divided by 7. As such, maximum scores can vary with a min of 0. The result is the DI, the disability index or functional disability index. The recall period is one week.
Time Frame
Day 85 and Day 113
Other Pre-specified Outcome Measures:
Title
Change from baseline of EHP-101 compared to placebo in Patient-Reported Outcomes Measurement Information system-29 Short
Description
(PROMIS)-29 Short measures self-reported physical, mental wellbeing. It consists of 29 questions. The questions are ranked on a 5-point Likert Scale.
Time Frame
Day 85
Title
Change from baseline of EHP-101 compared to placebo in 5 dimensions Itch Score
Description
5-D Itch Score comprises the following 5 dimensions: degree, duration, direction, disability and distribution. The recall period is two weeks.
Time Frame
Day 85
Title
Change from baseline of EHP-101 compared to placebo in University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Questionnaire
Description
The UCLA SCTC GIT 2.0 has 7 multi-item scales: Reflux, Distension/Bloating, Diarrhea, Fecal Soilage, Constipation, Emotional Well-being, and Social Functioning and a total GIT score. All scales are scored from 0 [better health-related quality of life (HRQOL)] to 3 (worse HRQOL) except the diarrhea and constipation scales (ranges 0-2 and 0-2.5, respectively). The Total GIT Score, is developed by averaging 6 of 7 scales (excluding constipation). The recall period is one week.
Time Frame
Day 85
Title
Change from baseline of EHP-101 compared to placebo in Functional Assessment of Chronic Illness Therapy: Fatigue
Description
The FACIT Fatigue Scale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The composite score of all item will be used. The total score ranges from 0 to 52. The recall period is one week.
Time Frame
Day 85
Title
Change from baseline of EHP-101 compared to placebo in the European Quality of Life 5 Domain Questionnaire
Description
The EQ-5D descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).
Time Frame
Day 85
Title
Quantitation of drug plasma levels at different timepoints to determine trough
Description
To determine trough level plasma concentrations of drug substance of EHP 101
Time Frame
Day 113
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients male and female ≥18 years and ≤74 years at the time of consent;
American College of Rheumatology/ European League Against Rheumatism 2013 Criteria for SSc; dcSSc (skin thickening on upper arms, upper legs, or trunk);
Documented SSc for up to 6 years from the first non-Raynaud's phenomenon with a total mRSS of ≥15;
No new or increased doses of immunosuppressants medications within 3 months prior to Screening;
Effective method of contraception for participants and their partners.
Exclusion Criteria:
Severe or unstable Systemic Sclerosis (SSc) or SSc with end-stage organ failure;
Patient with FVC <60%;
History of clinically significant medical condition or concurrent medical therapies that would exclude the patient, preclude participation in the clinical trial, influence response to study product, or interfere with study assessments;
History of gastrointestinal dysmotility requiring total parenteral nutrition or hospitalization within 6 months before Visit 1;
Any one of the following values for laboratory tests at screening:
Haemoglobin <9 g/dL;
Neutrophils <1.0 x 10^9/L;
Platelets <75 x 10^9/L;
Estimated creatinine clearance <50 mL/min according to the Cockcroft-Gault equation;
Serum transaminases >2.0 x upper normal limit;
Total bilirubin ≥1.5 x upper limit of normal.
Facility Information:
Facility Name
Arizona Arthritis & Rheumatology Associates, P.C.
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Facility Name
Care Access Research - Huntington
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92648
Country
United States
Facility Name
Pacific Arthritis Care Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90045
Country
United States
Facility Name
UCLA Division of Rheumatology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Inland Rheumatology Clinical Trials
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Central Florida Pulmonary Group
City
Altamonte Springs
State/Province
Florida
ZIP/Postal Code
32701
Country
United States
Facility Name
Life Clinical Trials
City
Margate
State/Province
Florida
ZIP/Postal Code
33063
Country
United States
Facility Name
Novel Clinical Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33186
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60208
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Rutgers, The State University of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
ZIP/Postal Code
2050
Country
Australia
Facility Name
Footscray Hospital
City
Footscray
ZIP/Postal Code
3011
Country
Australia
Facility Name
Griffith University
City
Gold Coast
ZIP/Postal Code
9726
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
ZIP/Postal Code
6150
Country
Australia
Facility Name
Westmead Hospital
City
Sydney
ZIP/Postal Code
2145
Country
Australia
Facility Name
Wellington Hospital
City
Wellington
ZIP/Postal Code
6021
Country
New Zealand
Facility Name
Centro Reumatologico
City
Caguas
ZIP/Postal Code
00725
Country
Puerto Rico
Facility Name
Mindful Medical Research
City
San Juan
ZIP/Postal Code
00918
Country
Puerto Rico
Facility Name
University of Puerto Rico, Medical Sciences Campus
City
San Juan
ZIP/Postal Code
00935
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Diffuse Cutaneous Systemic Sclerosis
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