A Phase II, Blinded, Randomised, Placebo Controlled Clinical Trial to Determine the Safety and Effect on Pain and Function According to RAPID-3 of IHL-675A in Patients With Rheumatoid Arthritis
Overview
- Phase
- Phase 2
- Intervention
- IHL-675A
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Incannex Healthcare Ltd
- Enrollment
- 20
- Locations
- 10
- Primary Endpoint
- Change in pain and function
- Status
- Suspended
- Last Updated
- last year
Overview
Brief Summary
The goal of this randomised, double-blind, placebo-controlled Phase II clinical trial is to assess the safety and effect of of IHL-675A in rheumatoid arthritis patients on pain, and function according to RAPID-3.
128 volunteers will be enrolled and randomised to one of four treatments (32 subjects per treatment). Each treatment will be self-administered twice daily for 24 weeks.
The four treatments are:
- Treatment 1 - IHL-675A
- Treatment 2 - CBD
- Treatment 3 - HCQ
- Treatment 4 - Placebo
Detailed Description
This is a Phase II, double-blind, randomised, placebo-controlled clinical trial to assess the safety and effect of IHL-675A (a combination of cannabidiol (CBD) and hydroxychloroquine (HCQ)) on pain and function using the RAPID-3 patient reported outcome (PRO) in patients with Rheumatoid Arthritis. This study will compare IHL-675A to the component drugs, CBD and HCQ, as well as a placebo. The study will aim to enrol a total of 128 subjects across the 4 treatment groups (32 per group). The study will also assess structural changes in joint damage in an MRI sub-study using the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS). During the 28-day screening period, subjects will provide information on their demographics, medical history, history of inflammatory conditions and weight/body mass index (BMI). A physical exam, vital signs, and 12-lead ECG will be conducted. Urine and blood samples will be collected for urinalysis, to assess for pregnancy, the presence of illicit drugs and to detect any clinically significant outcomes that would exclude subjects from being eligible for the clinical trial and to measure erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. A series of questionnaires will be conducted to assess eligibility and mental health status. These questionnaires will be: * RAPID-3 * JC 66/68 * Health Assessment Questionnaire-Disability Index (HAQ-DI) * Columbia-Suicide Severity Rating Scale (C-SSRS) Subjects will also undergo an optical coherence tomography (OCT) eye examination to rule out retinopathy. Subjects who have consented to the MRI sub-study will also undergo an MRI during screening. Once the participant is deemed eligible to be enrolled in the study, the baseline visit will be performed and the participant will be randomised into one of the four treatment groups: * Treatment 1 - IHL-675A (150 mg CBD, 200 mg HCQ: two soft gel capsules each containing 75 mg CBD and 100 mg HCQ twice per day for a total daily dose of 300 mg CBD and 400 mg HCQ) * Treatment 2 - CBD (150 mg: two capsules each containing 75 mg CBD twice per day for a total daily dose of 300 mg CBD) * Treatment 3 - HCQ (200 mg: two capsules each containing 100 mg HCQ twice per day for a total daily dose of 400 mg HCQ) * Treatment 4 - Placebo (two capsules twice per day). Subjects will visit the clinic on Day 1 and undergo baseline assessments, including: * RAPID-3 * JC 66/68 * ACR20 * CDAI-RA * FACIT-F * HAQ-DI * AE * Concomitant medication review * Weight/BMI * Physical exam * Vitals * ECG * Safety blood collection Subjects will then be supplied with their first 28-day supply of their allocated treatment and will be set up with and instructed on the use of an electronic patient reported outcome (ePRO) either web based or using an app on the subject's personal device. The ePRO will be used daily by the subject to record pain, joint stiffness, tiredness, and use of other pain medication for the control of pain associated with arthritis. Every 4 weeks, subjects will return to the clinical to undergo the same assessments and to receive the next 28-day supply of their allocated treatment. At 24 weeks, subjects will take their final dose prior to their return to the clinical for the final time (and will not receive another supply of the treatment) where they will undergo the same assessments as well as a final OCT eye exam, and subjects in the MRI sub-study will undergo a final MRI.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects will be included in the study if they satisfy all the following criteria:
- •Must have given written informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects
- •Has been diagnosed with RA and on stable treatment for RA for at least 3 months prior to the screening visit
- •Subject has a RAPID-3 score of \>4.5 at screening
- •Male or female, aged 18 or older inclusive at the screening visit
- •Body mass index (BMI) of 18 to 32 kg/m2, inclusive, at screening
- •Has at least two swollen or tender joints on the JC 66/68 at screening
- •Subject is otherwise medically healthy (in the opinion of the investigator), as determined by pre-study medical history and without clinically significant abnormalities including:
- •Physical examination at screening without any additional clinically relevant findings apart from those consistent with RA in the opinion of the investigator.
- •Systolic blood pressure at screening in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine or semi-supine position.
Exclusion Criteria
- •Subjects will be excluded from the study if there is evidence of any of the following at screening.
- •Subjects will be excluded from the study if there is evidence of any of the following at screening.
- •Known hypersensitivity to any of the study drug ingredients (cannabis products, sesame oil, hydroxychloroquine or chloroquine)
- •History of any clinically significant (in the opinion of the investigator) disorder within the last 3 months including cardiovascular (cardiac disease or arrythmias), haematologic, pulmonary, hepatic, renal, or gastrointestinal (such as cholecystitis, Gilbert's syndrome) disorders, or connective tissue, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic, or any disorder within the last 3 months that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion or action of the study drug (in the opinion of the investigator). Note: a history of fully resolved childhood asthma is not exclusionary; a history of cholecystectomy is not exclusionary
- •Family history of QT issues
- •Currently taking or have taken hydroxychloroquine, chloroquine or any drugs containing HCQ or chloroquine within 3 months of screening
- •Taking more than 10 mg prednisone per day
- •Pregnant, lactating, planning to become pregnant
- •Known substance abuse or medical, psychological, or social conditions or significant psychiatric illness (defined as hospitalisation), suicidal ideation, or suicidal attempts that, in the opinion of the investigator, may interfere with the subjects inclusion in the clinical study or evaluation of the clinical study results
- •Regular consumption of \>10 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer \[4.9% Alc/Vol\], 100 mL wine \[12% Alc/Vol\], 30 mL spirit \[40% Alc/Vol\])
Arms & Interventions
IHL-675A
150 mg CBD, 200 mg HCQ: two soft gel capsules each containing 75 mg CBD and 100 mg HCQ twice per day for a total daily dose of 300 mg CBD and 400 mg HCQ
Intervention: IHL-675A
Cannabidiol
150 mg: two capsules each containing 75 mg CBD twice per day for a total daily dose of 300 mg CBD
Intervention: Cannabidiol
Hydroxychloroquine
200 mg: two capsules each containing 100 mg HCQ twice per day for a total daily dose of 400 mg HCQ
Intervention: Hydroxychloroquine
Placebo
Two capsules twice per day
Intervention: Placebo
Outcomes
Primary Outcomes
Change in pain and function
Time Frame: 24 weeks
Routine Assessment of Patient Index Data 3 (RAPID-3) questionnaire to assess pain and function in arthritis patients. RAPID-3 is a pooled index of the 3 patient-reported American College of Rheumatology RA Core Data Set measures: function, pain, and patient global estimate of status. Each of the 3 individual measures is scored 0 to 10, for a total of 30. Disease severity may be classified on the basis of RAPID3 scores: \>12 = high; 6.1-12 = moderate; 3.1-6 = low; \< or =3 = remission
Secondary Outcomes
- Safety and tolerability - Incidence of the use of concomitant medications for pain management(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - Vital signs - Temperature(4, 8, 12, 16, 20 and 24 weeks)
- Change in disease activity - ACR20(4, 8, 12, 16, 20 and 24 weeks)
- Change in disease activity - CDAI-RA(4, 8, 12, 16, 20 and 24 weeks)
- Change in inflammatory serology - Erythrocyte sedimentation rate (ESR)(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - 12-lead ECG(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - OCT Eye Exam(24 weeks)
- Safety and tolerability - Vital signs - Blood Pressure(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - Vital signs - Pulse Rate(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - Adverse Events(4, 8, 12, 16, 20 and 24 weeks)
- Change in fatigue - Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)(4, 8, 12, 16, 20 and 24 weeks)
- Change in inflammatory serology - C-Reactive Protein (CRP)(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - Vital signs - Respiratory Rate(4, 8, 12, 16, 20 and 24 weeks)
- Change in quality of life - Health Assessment Questionnaire - Disability Index (HAQ-DI)(4, 8, 12, 16, 20 and 24 weeks)
- Safety and tolerability - The Columbia Suicide Severity Rating Scale (C-SSRS)(24 weeks)
- Change in pain - Routine Assessment of Patient Index Data 3 (RAPID-3)(4, 8, 12, 16 and 20 weeks)
- Change in disease activity - JC66/68(4, 8, 12, 16, 20 and 24 weeks)
- Change in tiredness(24 weeks)
- Change in pain (daily)(24 weeks)
- Change in joint stiffness duration(24 weeks)
- Change in joint stiffness severity(24 weeks)
- Effect of IHL-675A on cytokines(12 and 24 weeks)