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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05942911




Registration number
NCT05942911
Ethics application status
Date submitted
15/05/2023
Date registered
12/07/2023
Date last updated
27/11/2023

Titles & IDs
Public title
Safety and Effect on Pain and Function According to RAPID-3 of IHL-675A in Patients With Rheumatoid Arthritis
Scientific title
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
Secondary ID [1] 0 0
IHL675ARAPhII
Universal Trial Number (UTN)
Trial acronym
CHAPPII
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IHL-675A
Treatment: Drugs - Cannabidiol
Treatment: Drugs - Hydroxychloroquine
Treatment: Drugs - Placebo

Experimental: 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

Active comparator: Cannabidiol - 150 mg: two capsules each containing 75 mg CBD twice per day for a total daily dose of 300 mg CBD

Active comparator: Hydroxychloroquine - 200 mg: two capsules each containing 100 mg HCQ twice per day for a total daily dose of 400 mg HCQ

Placebo comparator: Placebo - Two capsules twice per day


Treatment: Drugs: IHL-675A
Combination product containing CBD and HCQ UniGel™ technology by ProCaps®. IHL-675A consists of a solid, film coated HCQ tablet that is contained within a CBD oil solution gel cap. Each IHL-675A gel cap contains 75 mg of CBD and 100 mg HCQ.

Treatment: Drugs: Cannabidiol
Formulated using UniGel™ technology by ProCaps®. The CBD soft gel capsules contain 75 mg CBD oil solution. These capsules look identical to the IHL-675A UniGel™ capsules, to aid double-blinding

Treatment: Drugs: Hydroxychloroquine
Formulated using UniGel™ technology by ProCaps®. The soft gel capsules each contain a 100 mg HCQ tablet. These capsules look identical to the IHL-675A UniGel™ capsules to aid double-blinding.

Treatment: Drugs: Placebo
Formulated using UniGel™ technology by ProCaps®. The soft gel capsules contain the inactive ingredients of the IHL-675A capsules and no active ingredients. These capsules look identical to the IHL-675A UniGel™ capsules to aid double-blinding.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in pain and function
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Safety and tolerability - Incidence of the use of concomitant medications for pain management
Timepoint [1] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [2] 0 0
Safety and tolerability - Vital signs - Temperature
Timepoint [2] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [3] 0 0
Safety and tolerability - Vital signs - Pulse Rate
Timepoint [3] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [4] 0 0
Safety and tolerability - Vital signs - Respiratory Rate
Timepoint [4] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [5] 0 0
Safety and tolerability - Vital signs - Blood Pressure
Timepoint [5] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [6] 0 0
Safety and tolerability - 12-lead ECG
Timepoint [6] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [7] 0 0
Safety and tolerability - Adverse Events
Timepoint [7] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [8] 0 0
Safety and tolerability - OCT Eye Exam
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
Safety and tolerability - The Columbia Suicide Severity Rating Scale (C-SSRS)
Timepoint [9] 0 0
24 weeks
Secondary outcome [10] 0 0
Change in pain - Routine Assessment of Patient Index Data 3 (RAPID-3)
Timepoint [10] 0 0
4, 8, 12, 16 and 20 weeks
Secondary outcome [11] 0 0
Change in fatigue - Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Timepoint [11] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [12] 0 0
Change in quality of life - Health Assessment Questionnaire - Disability Index (HAQ-DI)
Timepoint [12] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [13] 0 0
Change in disease activity - ACR20
Timepoint [13] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [14] 0 0
Change in disease activity - JC66/68
Timepoint [14] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [15] 0 0
Change in disease activity - CDAI-RA
Timepoint [15] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [16] 0 0
Change in inflammatory serology - C-Reactive Protein (CRP)
Timepoint [16] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [17] 0 0
Change in inflammatory serology - Erythrocyte sedimentation rate (ESR)
Timepoint [17] 0 0
4, 8, 12, 16, 20 and 24 weeks
Secondary outcome [18] 0 0
Change in tiredness
Timepoint [18] 0 0
24 weeks
Secondary outcome [19] 0 0
Change in pain (daily)
Timepoint [19] 0 0
24 weeks
Secondary outcome [20] 0 0
Change in joint stiffness duration
Timepoint [20] 0 0
24 weeks
Secondary outcome [21] 0 0
Change in joint stiffness severity
Timepoint [21] 0 0
24 weeks
Secondary outcome [22] 0 0
Effect of IHL-675A on cytokines
Timepoint [22] 0 0
12 and 24 weeks

Eligibility
Key inclusion criteria
Subjects will be included in the study if they satisfy all the following criteria:

1. 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
2. Has been diagnosed with RA and on stable treatment for RA for at least 3 months prior to the screening visit
3. Subject has a RAPID-3 score of >4.5 at screening
4. Male or female, aged 18 or older inclusive at the screening visit
5. Body mass index (BMI) of 18 to 32 kg/m2, inclusive, at screening
6. Has at least two swollen or tender joints on the JC 66/68 at screening
7. Subject is otherwise medically healthy (in the opinion of the investigator), as determined by pre-study medical history and without clinically significant abnormalities including:

1. Physical examination at screening without any additional clinically relevant findings apart from those consistent with RA in the opinion of the investigator.
2. 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.
3. Pulse rate at screening in the range of 45 to 100 beats/minute after 5 minutes rest in supine or semi-supine position.
4. Body temperature (tympanic) at screening between 35.5°C and 37.5°C.
5. Electrocardiogram (ECG) at screening without clinically significant abnormal findings including QT interval corrected for Fredericia (QTcF) =470msec for females and =450msec for males.
8. Physically well, in the opinion of the investigator, with no severe psychiatric, cardiac, renal, endocrine, gastrointestinal, bleeding, thyroid, cholesterol, or hypertension disorders
9. Male subjects must:

1. Agree not to donate sperm from the time of signing consent until at least 340 days (t1/2 *5 +90 days) after the last dose of study drug
2. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception (Appendix 10) from the time of signing consent until at least 340 days after the last dose of study drug).
3. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom from the time of signing consent until at least 340 days after the last dose of study drug.
10. Female subjects must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or, if of childbearing potential (Women who have been surgically sterilised through tubal ligation are permitted to participate, if they agree to use an additional barrier method of contraception from one month prior to the first dose of study drug, until at least 280 days (t1/2 * 5 +30 days) after the last dose of study drug.):

1. Must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to administration of the first dose of study drug. Note: subjects must also have a negative urine pregnancy test at each clinic visit.
2. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 280 days after the last dose of study drug.
3. If not exclusively in a same-sex relationship, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception (Appendix 10) from one month prior the first dose of study drug until at least 280 days after the last dose of study drug).
11. Able to avoid strenuous exercise from 72 hours prior to each visit to the clinical unit
12. Fluent in written and spoken English
13. Willing and able to comply with all study required tasks, including the completion of questionnaires, and to adhere to the study schedule and restrictions, as instructed by the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

1. Known hypersensitivity to any of the study drug ingredients (cannabis products, sesame oil, hydroxychloroquine or chloroquine)
2. 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
3. Family history of QT issues
4. Currently taking or have taken hydroxychloroquine, chloroquine or any drugs containing HCQ or chloroquine within 3 months of screening
5. Taking more than 10 mg prednisone per day
6. Pregnant, lactating, planning to become pregnant
7. 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
8. 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])
9. Positive urine illicit drug test at screening
10. C-SSRS score =4 OR reported suicidal behaviour within the past 3 months
11. Hepatic or renal impairment or disease defined as aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN), estimated glomerular filtration rate (eGFR) <60 at screening
12. Subject has retinopathy or history thereof (as determined by the OCT eye examination at screening)
13. A positive test result for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
14. History of gastrointestinal disorders which may impact absorption, distribution, metabolism and/or excretion of the IP (such as cholecystitis, cholecystectomy, Gilbert's syndrome)
15. Participation in another clinical trial of an investigational drug within 30 Days or 5 half-lives of the investigational drug (whichever is longer) prior to screening
16. Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the subject unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

MRI Sub-Study Inclusion Criteria:

Subjects may also participate in the MRI Sub-Study based on the below inclusion criteria.

1. Must have given written informed consent to participate in the MRI sub-study
2. Able and willing to undergo an MRI
3. Have at least 1 swollen and/or tender joint in left or right wrist or hand
4. Have a RAMRIS synovitis score of at least 1

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
128
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Paratus Clinical (Woden Dermatology) - Phillip
Recruitment hospital [2] 0 0
Genesis Research Services - Broadmeadow
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
Novatrials - Kotara
Recruitment hospital [5] 0 0
Emeritus Research - Sydney
Recruitment hospital [6] 0 0
Coast Joint Care - Maroochydore
Recruitment hospital [7] 0 0
AusTrials Westside (Taringa) - Taringa
Recruitment hospital [8] 0 0
AusTrials Wellers Hill - Wellers Hill
Recruitment hospital [9] 0 0
Emeritus Research Melbourne - Camberwell
Recruitment hospital [10] 0 0
Captain Sterling Medical Centre - Nedlands
Recruitment postcode(s) [1] 0 0
2606 - Phillip
Recruitment postcode(s) [2] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
2289 - Kotara
Recruitment postcode(s) [5] 0 0
2019 - Sydney
Recruitment postcode(s) [6] 0 0
4558 - Maroochydore
Recruitment postcode(s) [7] 0 0
4068 - Taringa
Recruitment postcode(s) [8] 0 0
4121 - Wellers Hill
Recruitment postcode(s) [9] 0 0
3124 - Camberwell
Recruitment postcode(s) [10] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Incannex Healthcare Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT05942911
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stephen Hall, Prof.
Address 0 0
Emeritus Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Mark Bleackley, PhD
Address 0 0
Country 0 0
Phone 0 0
-61 (0) 400 423 364
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05942911