Evaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Diffuse Cutaneous Systemic Sclerosis
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Interventions
- Drug: Patients will be randomized to receive EHP-101 or Placebo
- Registration Number
- NCT04166552
- Lead Sponsor
- Emerald Health Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 36
- 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.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EHP-101 low dose once a day Patients will be randomized to receive EHP-101 or Placebo - EHP-101 low dose twice a day Patients will be randomized to receive EHP-101 or Placebo - EHP-101 high dose once a day Patients will be randomized to receive EHP-101 or Placebo - EHP-101 high dose twice a day Patients will be randomized to receive EHP-101 or Placebo -
- Primary Outcome Measures
Name Time Method Incidence and severity of Treatment Emergent Adverse Events Day 113 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
Name Time Method Treatment effect of EHP-101 compared to placebo as measured by the American College of Rheumatology composite response index in diffuse cutaneous Systemic Sclerosis Day 85 and Day 113 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 Day 85 and Day 113 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 Scleroderma Health Assessment Questionnaire - Disability Index Day 85 and Day 113 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.
Treatment effect of EHP-101 compared to placebo in forced vital capacity percent predicted Day 85 and Day 113 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 Day 85 and Day 113 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 Day 85 and Day 113 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.
Trial Locations
- Locations (23)
UCLA Division of Rheumatology
🇺🇸Los Angeles, California, United States
Rutgers, The State University of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Inland Rheumatology Clinical Trials
🇺🇸Upland, California, United States
Pacific Arthritis Care Center
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Arizona Arthritis & Rheumatology Associates, P.C.
🇺🇸Phoenix, Arizona, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Mindful Medical Research
🇵🇷San Juan, Puerto Rico
Yale University
🇺🇸New Haven, Connecticut, United States
Care Access Research - Huntington
🇺🇸Huntington Beach, California, United States
Central Florida Pulmonary Group
🇺🇸Altamonte Springs, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Footscray Hospital
🇦🇺Footscray, Australia
Griffith University
🇦🇺Gold Coast, Australia
Westmead Hospital
🇦🇺Sydney, Australia
Wellington Hospital
🇳🇿Wellington, New Zealand
Novel Clinical Research Center
🇺🇸Miami, Florida, United States
Fiona Stanley Hospital
🇦🇺Murdoch, Australia
Life Clinical Trials
🇺🇸Margate, Florida, United States
Centro Reumatologico
🇵🇷Caguas, Puerto Rico
University of Puerto Rico, Medical Sciences Campus
🇵🇷San Juan, Puerto Rico