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

NCT ID: NCT04286789

Last Updated: 2021-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-22
• Study Completion Date: 2021-10-12

Brief 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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ORTD-1-Low Dose

5.6 mg/0.45 mL of active study drug

Group Type: EXPERIMENTAL

Low dose ORTD-1

Intervention Type: DRUG

Once weekly, single subcutaneous injection of ORTD-1 at a volume of 0.45 mL. Six weekly treatments; 28-day follow-up period.

Vehicle Control -Low Dose

Vehicle (Identical formulation without the active DP)

Group Type: PLACEBO_COMPARATOR

Low dose vehicle control

Intervention Type: DRUG

Once weekly subcutaneous injection of vehicle at a volume of 0.45 mL. Six weekly treatments; 28-day follow-up period.

ORTD 1-High Dose

22.5 mg/1.8 mL of active study drug

Group Type: EXPERIMENTAL

High dose ORTD-1

Intervention Type: DRUG

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.

Vehicle Control -High Dose

Vehicle (Identical formulation without the active DP)

Group Type: PLACEBO_COMPARATOR

High dose vehicle control

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

ORTD-1; Placebo; ORTD-1; Placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oryn Therapeutics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Stohl, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Keck School of Medicine of USC Division of Rheumatology

Locations

Keck School of Medicine of USC Division of Rheumatology

Los Angeles, California, United States

Orange County Research Center

Tustin, California, United States

Advanced Pharma CR, LLC

Miami, Florida, United States

Countries

United States

Other Identifiers

ORTD1-002

Identifier Type: -

Identifier Source: org_study_id