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

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 arecarried 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 monthsprior 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), asdetermined by pre-study medical history and without clinically significantabnormalities including:

8. Physical examination at screening without any additional clinically relevantfindings apart from those consistent with RA in the opinion of theinvestigator.

9. Systolic blood pressure at screening in the range of 90 to 160 mmHg anddiastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes insupine or semi-supine position.

10. Pulse rate at screening in the range of 45 to 100 beats/minute after 5 minutesrest in supine or semi-supine position.

11. Body temperature (tympanic) at screening between 35.5°C and 37.5°C.

12. Electrocardiogram (ECG) at screening without clinically significant abnormalfindings including QT interval corrected for Fredericia (QTcF) ≤470msec forfemales and ≤450msec for males.

13. Physically well, in the opinion of the investigator, with no severe psychiatric,cardiac, renal, endocrine, gastrointestinal, bleeding, thyroid, cholesterol, orhypertension disorders

14. Male subjects must:

15. Agree not to donate sperm from the time of signing consent until at least 340days (t1/2 *5 +90 days) after the last dose of study drug

16. If engaging in sexual intercourse with a female partner who could becomepregnant, must agree to use adequate contraception (defined as use of a condomplus a highly effective method of contraception (Appendix 10) from the time ofsigning consent until at least 340 days after the last dose of study drug).

17. If engaging in sexual intercourse with a female partner who is not ofchildbearing potential or a same-sex partner, must agree to use a condom fromthe time of signing consent until at least 340 days after the last dose ofstudy drug.

18. Female subjects must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeksbefore screening) or postmenopausal (where postmenopausal is defined as no mensesfor 12 months without an alternative medical cause and a follicle-stimulatinghormone (FSH) level consistent with postmenopausal status, per local laboratoryguidelines), or, if of childbearing potential (Women who have been surgicallysterilised through tubal ligation are permitted to participate, if they agree to usean additional barrier method of contraception from one month prior to the first doseof study drug, until at least 280 days (t1/2 * 5 +30 days) after the last dose ofstudy drug.):

19. Must have a negative serum pregnancy test at screening and a negative urinepregnancy 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.

20. Must agree not to donate ova or attempt to become pregnant from the time ofsigning consent until at least 280 days after the last dose of study drug.

21. If not exclusively in a same-sex relationship, must agree to use adequatecontraception (which is defined as use of a condom by the male partner combinedwith use of a highly effective method of contraception (Appendix 10) from onemonth prior the first dose of study drug until at least 280 days after the lastdose of study drug).

22. Able to avoid strenuous exercise from 72 hours prior to each visit to the clinicalunit

23. Fluent in written and spoken English

24. Willing and able to comply with all study required tasks, including the completionof questionnaires, and to adhere to the study schedule and restrictions, asinstructed by the protocol.

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) disorderwithin 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, uncontrolledendocrine/metabolic, oncologic (within the last 5 years), neurologic, or anydisorder within the last 3 months that may prevent the successful completion of thestudy or influence the absorption, distribution, metabolism, excretion or action ofthe study drug (in the opinion of the investigator). Note: a history of fullyresolved childhood asthma is not exclusionary; a history of cholecystectomy is notexclusionary

3. Family history of QT issues

4. Currently taking or have taken hydroxychloroquine, chloroquine or any drugscontaining 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 significantpsychiatric illness (defined as hospitalisation), suicidal ideation, or suicidalattempts that, in the opinion of the investigator, may interfere with the subjectsinclusion 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), estimatedglomerular filtration rate (eGFR) <60 at screening

12. Subject has retinopathy or history thereof (as determined by the OCT eye examinationat 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 screeningvisit.

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 (ordelegate) would make the subject unsuitable for this study, including inability tocooperate fully with the requirements of the study protocol or likelihood ofnoncompliance 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