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

NCT04286789 | Completed Phase 1 FDA Drug

• 1 other identifier: ORTD1-002
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Immunogenicity by measurement of anti-drug antibodies

  Weeks 1, 3, 5, and 10

• Serum concentration of ORTD-1 from baseline

  10 weeks

• Cmax of ORTD-1

  Week 1 through week 6

• Tmax of ORTD-1

  Week 1 through week 6

Other Outcomes (1)

• Change from baseline in disease activity

  Weeks 1, 3, 5, and 10

Study Arms (4)

ORTD-1-Low Dose

EXPERIMENTAL

5.6 mg/0.45 mL of active study drug

Drug: Low dose ORTD-1

Vehicle Control -Low Dose

PLACEBO COMPARATOR

Vehicle (Identical formulation without the active DP)

Drug: Low dose vehicle control

ORTD 1-High Dose

EXPERIMENTAL

22.5 mg/1.8 mL of active study drug

Drug: High dose ORTD-1

Vehicle Control -High Dose

PLACEBO COMPARATOR

Vehicle (Identical formulation without the active DP)

Drug: High dose vehicle control

Interventions

Low dose ORTD-1 DRUG

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

Also known as: ORTD-1

ORTD-1-Low Dose

Low dose vehicle control DRUG

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

Also known as: Placebo

Vehicle Control -Low Dose

High dose ORTD-1 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.

Also known as: ORTD-1

ORTD 1-High Dose

High dose vehicle control 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.

Also known as: Placebo

Vehicle Control -High Dose

Eligibility Criteria

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

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oryn Therapeutics, LLC: lead

Study Sites (3)

Keck School of Medicine of USC Division of Rheumatology

Los Angeles, California, 90033, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33147, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

rhesus-theta-defensin-1

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• William Stohl, M.D., Ph.D.

  Keck School of Medicine of USC Division of Rheumatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: February 27, 2020
• Study Start: March 22, 2021
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: October 19, 2021

Record last verified: 2021-10

Locations

US (3)