Safety and Effect on Pain and Function According to RAPID-3 of IHL-675A in Patients With Rheumatoid Arthritis

NCT05942911 | Terminated Phase 2

• 1 other identifier: IHL675ARAPhII
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

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

Conditions

Rheumatoid Arthritis

Keywords

Arthritis; MRI; RA; Rheumatoid Arthritis; Pain; Fatigue; RAMRIS; RAPID-3; Cannabidiol; CBD; Hydroxychloroquine; HCQ; Placebo; IHL-67A; Incannex; Joint pain; Stiffness

Outcome Measures

Primary Outcomes (1)

• Change in pain and function

  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

  24 weeks

Secondary Outcomes (22)

• 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

• Safety and tolerability - Vital signs - Pulse Rate

  4, 8, 12, 16, 20 and 24 weeks

• Safety and tolerability - Vital signs - Respiratory Rate

  4, 8, 12, 16, 20 and 24 weeks

• Safety and tolerability - Vital signs - Blood Pressure

  4, 8, 12, 16, 20 and 24 weeks

Other Outcomes (1)

• Structural effects of IHL-675A

  24 weeks

Study Arms (4)

IHL-675A

EXPERIMENTAL

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

Drug: IHL-675A

Cannabidiol

ACTIVE COMPARATOR

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

Drug: Cannabidiol

Hydroxychloroquine

ACTIVE COMPARATOR

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

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

Two capsules twice per day

Drug: Placebo

Interventions

Placebo DRUG

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.

Placebo

IHL-675A DRUG

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.

IHL-675A

Cannabidiol DRUG

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

Also known as: CBD, Epidiolex, Epydiolex

Cannabidiol

Hydroxychloroquine DRUG

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.

Also known as: HCQ, Plaquenil

Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• 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
• 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 \[40% Alc/Vol\])
• Positive urine illicit drug test at screening
• C-SSRS score ≥4 OR reported suicidal behaviour within the past 3 months
• 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
• Subject has retinopathy or history thereof (as determined by the OCT eye examination at screening)
• 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.
• History of gastrointestinal disorders which may impact absorption, distribution, metabolism and/or excretion of the IP (such as cholecystitis, cholecystectomy, Gilbert's syndrome)
• 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

Sponsors & Collaborators

• Incannex Healthcare Ltd: lead

Study Sites (10)

Paratus Clinical (Woden Dermatology)

Phillip, Australian Capital Territory, 2606, Australia

Location

Genesis Research Services

Broadmeadow, New South Wales, 2292, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Novatrials

Kotara, New South Wales, 2289, Australia

Location

Emeritus Research

Sydney, New South Wales, 2019, Australia

Location

Coast Joint Care

Maroochydore, Queensland, 4558, Australia

Location

AusTrials Westside (Taringa)

Taringa, Queensland, 4068, Australia

Location

AusTrials Wellers Hill

Wellers Hill, Queensland, 4121, Australia

Location

Emeritus Research Melbourne

Camberwell, Victoria, 3124, Australia

Location

Captain Sterling Medical Centre

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis; Pain; Fatigue; Arthralgia

Interventions

Cannabidiol; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephen Hall, Prof.

  Emeritus Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2023
• First Posted: July 12, 2023
• Study Start: November 22, 2023
• Primary Completion: October 28, 2024
• Study Completion: October 28, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

AU (10)