Evaluation of Safety, Tolerability and Preliminary Efficacy of EHP-101 in Diffuse Cutaneous Systemic Sclerosis

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

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).

Study Overview

• Status: Suspended
• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Drug: Patients will be randomized to receive EHP-101 or Placebo; Drug: Patients will be randomized to receive EHP-101 or Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital
  • Footscray, Australia, 3011
    • Footscray Hospital
  • Gold Coast, Australia, 9726
    • Griffith University
  • Murdoch, Australia, 6150
    • Fiona Stanley Hospital
  • Sydney, Australia, 2145
    • Westmead Hospital
• New Zealand
  • Wellington, New Zealand, 6021
    • Wellington Hospital
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Centro Reumatologico
  • San Juan, Puerto Rico, 00918
    • Mindful Medical Research
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico, Medical Sciences Campus
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Arizona Arthritis & Rheumatology Associates, P.C.
  • California
    • Huntington Beach, California, United States, 92648
      • Care Access Research - Huntington
    • Los Angeles, California, United States, 90095
      • UCLA Division of Rheumatology
    • Los Angeles, California, United States, 90045
      • Pacific Arthritis Care Center
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Central Florida Pulmonary Group
    • Margate, Florida, United States, 33063
      • LIFE Clinical Trials
    • Miami, Florida, United States, 33186
      • Novel Clinical Research Center
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers, The State University of New Jersey
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EHP-101 low dose once a day	Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken once a day; Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken twice a day
Experimental: EHP-101 low dose twice a day	Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken once a day; Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken twice a day
Experimental: EHP-101 high dose once a day	Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken once a day; Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken twice a day
Experimental: EHP-101 high dose twice a day	Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken once a day; Drug: Patients will be randomized to receive EHP-101 or Placebo; EHP-101 or placebo will be taken twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 85 and Day 113
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.	Day 85 and Day 113
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%	Day 85 and Day 113
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.	Day 85 and Day 113
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.	Day 85 and Day 113
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.	Day 85 and Day 113

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of EHP-101 compared to placebo in Patient-Reported Outcomes Measurement Information system-29 Short	(PROMIS)-29 Short measures self-reported physical, mental wellbeing. It consists of 29 questions. The questions are ranked on a 5-point Likert Scale.	Day 85
Change from baseline of EHP-101 compared to placebo in 5 dimensions Itch Score	5-D Itch Score comprises the following 5 dimensions: degree, duration, direction, disability and distribution. The recall period is two weeks.	Day 85
Change from baseline of EHP-101 compared to placebo in University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Questionnaire	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.	Day 85
Change from baseline of EHP-101 compared to placebo in Functional Assessment of Chronic Illness Therapy: Fatigue	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.	Day 85
Change from baseline of EHP-101 compared to placebo in the European Quality of Life 5 Domain Questionnaire	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).	Day 85
Quantitation of drug plasma levels at different timepoints to determine trough	To determine trough level plasma concentrations of drug substance of EHP 101	Day 113

Collaborators and Investigators

• Sponsor: Emerald Health Pharmaceuticals

Publications and helpful links

Helpful Links

• sponsor webpage

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 16, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: skin disease; Scleroderma; connective tissue disease; Systemic sclerosis; diffuse; EHP-101 Oral Solution; dcSSc; pathological processes
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: EHP-101-SS01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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