MH004 Topical Cream in Healthy Adult Volunteers and Participants With Atopic Dermatitis or Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 April 2021
• Main ID: NCT04815148
• Date of registration: 19/03/2021
• Prospective Registration: Yes
• Primary sponsor: Minghui Pharmaceutical Pty Ltd
• Public title: MH004 Topical Cream in Healthy Adult Volunteers and Participants With Atopic Dermatitis or Rheumatoid Arthritis
• Scientific title: A Phase Ia/Ib Study to Evaluate the Safety, Tolerability and PK of MH004 Topical Cream in Healthy Adult Volunteers and to Investigate Its Efficacy and Safety Profile in Participants With Atopic Dermatitis or Rheumatoid Arthritis
• Date of first enrolment: April 1, 2021
• Target sample size: 72
• Recruitment status: Not yet recruiting
• URL: https://clinicaltrials.gov/show/NCT04815148
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Key inclusion & exclusion criteria

Inclusion Criteria:

Phase Ia and Ib:

1. Phase Ia: Adults, age 18 - 45 years old, inclusive, at time of screening. Phase Ib:
Adults, age 18 - 70 years old, inclusive, at time of screening.

2. Willing and able to understand and sign an informed consent form and to comply with
all aspects of the protocol.

3. Participants whose body mass index (BMI) at screening is within a range of = 18.5
kg/m2 and <35 kg/m2.

(BMI = Body Weight (kg) / [Height (m) × Height (m)])

4. Has abstained from smoking or use of tobacco products from 6 months prior to study
drug administration and for the entire duration of the study.

5. Participant's medical history shows no contraindication to JAK inhibitors.

6. Participants judged to be in good health by the Investigator based upon the results of
physical examinations (PEs), 12-lead electrocardiogram (ECG) test, and all items of
routine laboratory tests, including serum biochemistry, hematology and urinalysis, are
within normal range, or if outside normal range they are deemed not clinically
significant as judged by the Investigator. Assessment items of blood biochemistry
include albumin, total protein, total bilirubin, ALP, SGOT, SGPT, BUN, serum
creatinine, CK and fasting lipid profile (total cholesterol, LDL, HDL and
triglycerides). Assessment items of hematology tests include RBC count, WBC with
differential counts, hemoglobin, hematocrit and platelet count. Assessment items of
urinalysis include pH, colour, appearance, gravity, erythrocyte, leukocyte, glucose,
protein, ketones and nitrite.

For the ECG test, QTcF must be =450msec for females or males, and PR interval <120msec
and no evidence of bundle branch block.

7. Willingness of men and women of reproductive potential to observe conventional and
highly effective birth control from the beginning of the study screening until 6
months after receiving the last treatment of investigational product. A highly
effective method of contraception is defined as follows:

Highly Effective Methods That Have Low User Dependency

- Implantable progestogen-only hormone contraception associated with inhibition of
ovulation.

- Intrauterine device (IUD).

- Intrauterine hormone-releasing system (IUS).

- Bilateral tubal occlusion.

- Vasectomized partner (is a highly effective contraceptive method provided that
the partner is the sole sexual partner of the WOCBP and the absence of sperm has
been confirmed. If not, an additional highly effective method of contraception
should be used. The spermatogenesis cycle is approximately 90 days.

Highly Effective Methods That Are User Dependent (must be used in combination with a
male or female condom)

- Combined (estrogen- and progestogen-containing) hormonal contraception associated
with inhibition of ovulation: oral, intravaginal, transdermal, injectable.

- Progestogen-only hormone contraception associated with inhibition of ovulation:
oral, injectable.

8. WOCBP must have a negative pregnancy test at Screening and Day 1 and be willing to
have additional pregnancy tests as required throughout the study.

9. Males must not donate sperm for at least 90 days after the last dose of study drug.

10. Participants are a current non-smoker (and has not smoked in the 6 months prior to
baseline) and will not smoke throughout the course of the study. Screening cotinine
test must be negative.

Additional Inclusion criteria for Phase Ib (Study 2-1, AD participants):

11. Participants who are diagnosed with mild to moderate atopic dermatitis for =3 months
prior to screening based on the Hanifin and Rajka Criteria. Mild to moderate AD is
defined as BSA 2-20%; EASI 3-16; IGA 2 - 3 at both the screening and Day 1 visit.

12. Participants with a Target Area of Atopic Dermatitis of approx. 10 x 10cm on any part
of the body other than the scalp, face, palms of hands, soles of feet, buttocks or
groin to apply the Study Drug. The Target Lesion Area score needs to be between mild
(2) to moderate (3) on the Disease Affected Eczema Area and Severity Indices (EASI) at
screening and Day 1.

13. Participant is able to apply the study drug to the Target Lesion Area; or if the
Target Lesion is not easily reached (i.e. on their back), has someone who is willing
and able to apply the study drug as prescribed during the treatment period.

14. Participants who agree to discontinue all treatment used for their AD, such as topical
antihistamines, topical antimicrobials, topical or oral corticosteroid, systemic
immune modulating agents and light treatments, as well as bleach baths and avoid
prolonged sun exposure during the study period for/on the affected site(s) (except the
standard medication oral antihistamine levocetirizine and rescue medication prescribed
by the study Investigator(s)). Participants who are taking oral antihistamines need to
be on a stable dose for at least 2 months.

15. Participants are required to stop using prohibited topical treatments for at least 14
days before the first investigational drug dose administration (or longer if the
treatment half-life requires so 5 half-lives should have elapsed) and prohibited
systemic treatment drugs for 28 days before the first investigational drug dose
administration (or longer if the treatment half-life requires so 5 half-lives should
have elapsed).

Additional Inclusion criteria for Phase Ib (Study 2-2, RA participants):

16. Diagnosed with Rheumatoid arthritis (RA) prior to screening who fulfil the 2010
ACR/EULAR classification for RA.

17. Mild to moderate disease activity at screening (DAS 28-CRP = 4.5 and = 2.6).

18. Active RA in one Target Joint of either hand or wrist at screening and baseline where
both swelling and tenderness/pain is present.

Exclusion Criteria:

Phase Ia and Ib:

1. Participants with conditions at the study drug application site(s) that would
interfere with the study drug administration, skin assessment, or reaction to study
drug.

For example: presence of open sores; obvious differences in skin color between
applications sites/discolouration such as vitiligo; excessive hair; scar tissue;
tattoo.

2. Participants with any unstable health status, defined as having newly diagnosed
medical conditions or symptoms of a medical condition that is not yet diagnosed within
30 days prior to the first dose of the study drug.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Atopic Dermatitis

Intervention(s)

Drug: MH004 Ia(3%)

Drug: MH004 Ia(0.1%)

Drug: MH004 Ib-1(0.3%)

Drug: MH004 Ib-1(1%)

Drug: MH004 Ib-2(0.3%)

Drug: MH004 Ib-2(3%)

Drug: MH004 Ia(1%)

Drug: MH004 Ia(0.3%)

Drug: MH004 Ib-1(0.1%)

Drug: MH004 Ib-2(1%)

Primary Outcome(s)

To determine the maximum tolerated dose (MTD) of MH004 topical cream. [Time Frame: 1 year]

To establish the recommended phase 2 dose (RP2D). [Time Frame: 1 year]

To evaluate the incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability]. [Time Frame: 1 year]

Secondary Outcome(s)

Characterization of Pharmacokinetics (AUC) [Time Frame: Up to 6 Months]

Change from baseline Target Lesion EASI score [Time Frame: 1 year]

Characterization of Pharmacokinetics (Cmax) [Time Frame: Up to 6 Months]

Characterization of Pharmacokinetics (t1/2) [Time Frame: Up to 6 Months]

Change from baseline Target Joint swelling and tenderness score [Time Frame: 1 year]

Characterization of Pharmacokinetics (CL) [Time Frame: Up to 6 Months]

Secondary ID(s)

MH004-CP001EN

Source(s) of Monetary Support

Please refer to primary and secondary sponsors