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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04166552
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : June 28, 2022
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Diffuse Cutaneous Systemic Sclerosis Drug: Patients will be randomized to receive EHP-101 or Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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: Double (Participant, Investigator)
Masking Description: Double (intracohort)
Primary Purpose: Treatment
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
Actual Study Start Date : June 11, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : September 2022


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

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 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

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 twice a day




Primary Outcome Measures :
  1. Incidence and severity of Treatment Emergent Adverse Events [ Time Frame: 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 :
  1. Treatment effect of EHP-101 compared to placebo as measured by the American College of Rheumatology composite response index in diffuse cutaneous Systemic Sclerosis [ Time Frame: 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.

  2. Treatment effect of EHP-101 compared to placebo in modified Rodnan Skin Score [ Time Frame: 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.

  3. Treatment effect of EHP-101 compared to placebo in forced vital capacity percent predicted [ Time Frame: 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%

  4. Treatment effect of EHP-101 compared to placebo in physician global assessment score [ Time Frame: 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.

  5. Treatment effect of EHP-101 compared to placebo in patient global assessments score [ Time Frame: 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.

  6. Treatment effect of EHP-101 compared to placebo in Scleroderma Health Assessment Questionnaire - Disability Index [ Time Frame: 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.


Other Outcome Measures:
  1. Change from baseline of EHP-101 compared to placebo in Patient-Reported Outcomes Measurement Information system-29 Short [ Time Frame: Day 85 ]
    (PROMIS)-29 Short measures self-reported physical, mental wellbeing. It consists of 29 questions. The questions are ranked on a 5-point Likert Scale.

  2. Change from baseline of EHP-101 compared to placebo in 5 dimensions Itch Score [ Time Frame: Day 85 ]
    5-D Itch Score comprises the following 5 dimensions: degree, duration, direction, disability and distribution. The recall period is two weeks.

  3. Change from baseline of EHP-101 compared to placebo in University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Questionnaire [ Time Frame: Day 85 ]
    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.

  4. Change from baseline of EHP-101 compared to placebo in Functional Assessment of Chronic Illness Therapy: Fatigue [ Time Frame: Day 85 ]
    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.

  5. Change from baseline of EHP-101 compared to placebo in the European Quality of Life 5 Domain Questionnaire [ Time Frame: Day 85 ]
    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).

  6. Quantitation of drug plasma levels at different timepoints to determine trough [ Time Frame: Day 113 ]
    To determine trough level plasma concentrations of drug substance of EHP 101



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04166552


Contacts
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Contact: Amanda Hughes +1 858-832-4887 ahughes@emeraldpharma.com

Locations
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Sponsors and Collaborators
Emerald Health Pharmaceuticals
Additional Information:
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Responsible Party: Emerald Health Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04166552    
Other Study ID Numbers: EHP-101-SS01
First Posted: November 18, 2019    Key Record Dates
Last Update Posted: June 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Emerald Health Pharmaceuticals:
Scleroderma
Systemic sclerosis
EHP-101 Oral Solution
dcSSc
diffuse
pathological processes
connective tissue disease
skin disease
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases