Randomized, Double-blind, Vehicle Controlled, Repeat Dose Comparative Study in RA Patients Managed With DMARDs

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Parallel, Vehicle Controlled, Repeat Dose Comparative Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ORTD-1 in Rheumatoid Arthritis Patients With Mild Disease Managed With DMARDs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04286789
• Other study ID #: ORTD1-002
• Status: Completed
• Phase: Phase 1
• Start date: March 22, 2021
• Est. completion date: October 12, 2021

Study information

• Verified date: October 2021
• Source: Oryn Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, vehicle controlled, double-blind, repeat dose comparative study in patients with rheumatoid arthritis (RA) under management with DMARDs and with persistent disease activity. The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of 6 weekly repeat doses of ORTD-1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: October 12, 2021
• Est. primary completion date: October 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• =18 years of age or older, males or females.
• Diagnosed rheumatoid arthritis per the American Rheumatism Association 1987 classification criteria of at least 6 months duration.
• Disease activity defined as:
• erythrocyte sedimentation rate (ESR) > 24 mm or serum C-reactive protein level = 1.2 times (X) the upper limit of normal (ULN), and
• DAS28-CRP score = 2.6 and < 5.1
• Current regimen of DMARDs that may include methotrexate, sulfasalazine, hydroxychloroquine, leflunomide and/or azathioprine, alone or in combination.
• No change in DMARD dose(s) within 4 weeks prior to Screening.
• May be receiving a stable regimen (of at least 4 weeks duration) of concomitant NSAIDs.
• Women of child-bearing potential (WOCBP), defined as a sexually mature woman not surgically sterilized, or not post-menopausal for at least 12 consecutive months.

Female subjects must:

• Not be lactating; not be pregnant upon enrollment.
• Agree to use highly effective methods of birth control throughout the study. Highly effective methods of contraception include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation by oral, intravaginal, or transdermal administration; progestogen-only hormonal contraception associated with inhibition of ovulation by oral, injectable, or implantable administration; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; partner vasectomy; or total abstinence (only if total abstinence is an established method and lifestyle of the subject).
• Patients already using hormonal contraception at the time of screening will be eligible but will not initiate hormonal contraception in order to participate in the study.
• Agree to use highly effective methods of birth control for at least 6 months after the last dose of investigational product.
• Male subjects must refrain from donating sperm or fathering a child during the study.
• Male subjects must use barrier contraception throughout the course of the study.
• Signed and dated informed consent.

Exclusion Criteria:

• Prior therapy with any biologic therapeutic within 3 months prior to enrollment, or in the case of Rituxan (rituximab), this period must be at least 12 months.
• History of or current clinical fibromyalgia or Juvenile Idiopathic Arthritis (JIA).
• Positive diagnosis of SLE.
• Patients with Type 1 or Type 2 Diabetes Mellitus.
• Patients with psoriasis.
• Patients with skin condition(s) or visible abnormalities at or near potential sites of injection (right and left abdomen; right and left thigh) that could mask the assessment of safety.
• Acute illness including current or chronic infections requiring antibiotics, or symptoms of a resolving illness, within 2 weeks prior to study.
• Any investigational drug within 3 months prior to study.
• Patients may not be receiving systemic corticosteroid therapy with the exception of inhaled corticosteroids for the treatment of asthma.
• Any clinically relevant abnormality as assessed by the Investigator, on screening history, physical exam, clinical laboratory, chest X-ray, or ECG, other than values consistent with rheumatoid arthritis, with the exception that liver function tests (ALP, ALT, AST) may be up to 1.5 times (X) the upper limit of normal (ULN).
• Positive serological test for HCV, HBsAg, HBcAg, HIV.
• QuantiFERON-positive patients may be enrolled with documented evidence that they have completed a prescribed course of antituberculous therapy.
• History of cardiovascular disease with New York Heart Association (NYHA) functional class II or greater; or history of stroke, or uncontrolled hypertension.
• History of lymphoproliferative disease, or organ allograft.
• Pregnancy or lactation, or WOCBP not currently using contraceptives or male partners of WOCBP not currently using contraceptives.
• History of cancer (except for in situ cancer, or limited stage cancer of the cervix, head and neck (squamous cell), thyroid, or skin (non-melanomatous) curatively treated with no sign of disease for > 5 years).
• Any physical or psychological condition that might prevent complete participation in the study, in the view of the investigator.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Low dose ORTD-1
Once weekly, single subcutaneous injection of ORTD-1 at a volume of 0.45 mL. Six weekly treatments; 28-day follow-up period.
• Low dose vehicle control
Once weekly subcutaneous injection of vehicle at a volume of 0.45 mL. Six weekly treatments; 28-day follow-up period.
• High dose ORTD-1
Two subcutaneous injections of ORTD-1 at two injection sites once weekly; 0.90 mL of ORTD-1 per each subcutaneous injection. Six weekly treatments; 28-day follow-up period.
• High dose vehicle control
Two subcutaneous injections of vehicle at two injection sites once weekly; 0.90 mL of vehicle per each subcutaneous injection. Six weekly treatments; 28-day follow-up period.

Locations

Country	Name	City	State
United States	Keck School of Medicine of USC Division of Rheumatology	Los Angeles	California
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Oryn Therapeutics, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in disease activity	Disease activity score with C-reactive protein (DAS28-CRP) and ESR (Erythrocyte sedimentation rate) will be evaluated from the change in baseline (Visit 1) to Visit 9 (last patient visit). 28 joints are evaluated in the DAS28-CRP (Proximal interphalangeal, metacarpophalangeal, wrists, elbows, shoulders, knees) for swelling and tenderness. The overall calculated value for DAS28-CRP uses the number of swollen and tender joints, the value recorded from the patient's CRP, and the Global Health patient assessment (0-100 mm; where 0 is very good and 100 is very bad health condition).	Weeks 1, 3, 5, and 10
Primary	Safety and Tolerability of ORTD-1 measured by the number of patients with adverse events	Safety will be assessed throughout the duration of the study (weeks 1 through 10) by monitoring of adverse events.	10 weeks
Secondary	Immunogenicity by measurement of anti-drug antibodies	Immunogenicity is the measurement of anti-drug (ORTD-1) antibodies (ADA) in serum. ADA samples will be analyzed from the change in baseline (Visit 1) using descriptive statistics (mean, median, range and standard deviation).	Weeks 1, 3, 5, and 10
Secondary	Serum concentration of ORTD-1 from baseline	Serum concentration will be measured from the change in baseline (Visit 1) using descriptive statistics (mean, median, range and standard deviation).	10 weeks
Secondary	Cmax of ORTD-1	Cmax (maximum plasma concentration) will be measured using the arithmetic mean, standard deviation (SD), coefficient of variation (CV) (%), median, minimum, and maximum.	Week 1 through week 6
Secondary	Tmax of ORTD-1	Tmax (time of maximum plasma concentration) will be measured using the arithmetic mean, standard deviation (SD), coefficient of variation (CV) (%), median, minimum, and maximum.	Week 1 through week 6