Phase 1 Trial of Type II Collagen (CII) APL A12 in Rheumatoid Arthritis Patients

NCT01123655 | Completed Phase 1 Results DMC

• 1 other identifier: IMMA-007-08S
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I clinical trial to determine whether orally administered APL A12 at one or more doses is superior to placebo in effecting a 25% reduction in interferon (IFN) stimulation index in 1(II)-stimulated culture of peripheral blood mononuclear (PBMC) obtained from patients with Rheumatoid Arthritis (RA), which will be the primary outcome variable. In an effort to learn more about the mechanism of action of APL A12, the investigators will assess Th1/Th2/Th3 cytokine production in supernatants from 48h and 144h cultures of PBMC stimulated by 1(II) and by APL A12 above. The investigators will assess function of CD4+ CD25+ T regs to determine whether APL A12 improves their suppressive function. Flow cytometry combined with intracellular cytokine staining will be used in an effort to determine which T cell subset(s) is/are experiencing shifts in cytokine expression.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment.

  The primary outcome variable is the presence of a \> 25% reduction in net IFN concentration in supernatants of 1(II)-stimulated PBMC cultures from baseline after 16 weeks of treatment.

  16 weeks

Secondary Outcomes (33)

• Flow Cytometry

  baseline and 8 or 16 weeks

• Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up

  0 and16 weeks

• Change in Cytokine Profile From Baseline and 16 Weeks

  0 and 16 weeks

• Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks

  baseline and 8 or 16 wks

• Neutrophils Counts at 0 and 16 Weeks

  Baseline and 16 weeks

Study Arms (3)

Arm 1

EXPERIMENTAL

The study will have 3 treatment arms each with 10-12 patients who have demonstrated T cell immunity to CII and have an in vitro response to APL A12 at the screening visit. Patients will be randomized to one of the 2 treatment arms (30 micrograms APL A12 or placebo). Each of the 2 treatments will be given for 16 weeks. Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate. Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate.

Drug: APLA12; Drug: Placebo

Arm 2

EXPERIMENTAL

The next group will receive a higher dose (50 micrograms) and/or placebo (Block 2). Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate.

Drug: APLA12; Drug: Placebo

Arm 3

EXPERIMENTAL

Block 3 (Arm 3) will include placebo and both doses of APL/A12 to ensure 10-12 patients are enrolled in each arm ( total of approximately 32 subjects) so we will have 24 subjects who complete the 16 weeks of study treatment. Arms 2 and 3 will run simultaneously. Intervention: Drug treatment will be stopped or interrupted if indicated.

Drug: APLA12; Drug: Placebo

Interventions

APLA12 DRUG

Intervention: Drug treatment will be stopped or interrupted if indicated. Medical care will be provided at no cost to the patient.

Arm 1; Arm 2; Arm 3

Placebo DRUG

Drug treatment will be stopped or interrupted if indicated. Medical care will be provided at no cost to the patient.

Arm 1; Arm 2; Arm 3

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria for participation in the study.
• Male or female; age \> 18 years.
• American College of Rheumatology (ACR) 1988 revised criteria for rheumatoid arthritis.
• Onset of disease age 16 or older.
• Onset of disease at least 3 months prior to enrollment.
• RA patients ages 18-85 with RA of 3 month duration which in the opinion of the examining rheumatologist is "clinically stable" and will likely not require adjustment of doses of Disease-modifying antirheumatic drugs (DMARDS), NSAIDS, prednisone, anti-tumor necrosis factor (anti-TNF) alpha therapies for the 16 weeks of the treatment phase of the study.
• Patients must agree to discontinue all "herbal remedies" as described in this protocol.
• Women of childbearing age will be advised to use effective means of contraception for the treatment phase of the trial and for 90 days thereafter. They must have a negative urine pregnancy test at the randomization visit. (Required by the FDA.)
• Men will be advised to use effective means of contraception for the treatment phase of the trial and for 90 days thereafter. (Required by the FDA.)
• Crohn's Disease Activity Index (CDAI) less than or equal to 30 at the baseline visit.
• Patients with a past history of malignant neoplasm will be eligible if they are 1 or greater years with no recurrence of malignant neoplasm.

You may not qualify if:

• Inability to render an informed consent in accordance with institutional guidelines.
• Participation in another clinical research study involving the evaluation of another investigational drug within 90 days of entry into this study.
• RA patients on \>7.5 mg prednisone a day.
• RA patients with intra-articular corticosteroid injections during the previous 30 days.
• Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for the study. Hepatitis B abd/or C patients with inactive disease (as determined by PI) will be enrolled.
• Positive urine pregnancy test
• Age 85 years or greater.
• Use of "fish oil" within the previous 4 weeks of the baseline visit.
• Therapy consisting of auranofin or cyclophosphamide (all other DMARDs are allowed).
• Previous autologous or heterologous stem cell transplantation.
• Active malignant neoplasm or past treatment for malignant neoplasm 1 year from screening visit.
• Use of oral CII within the past 1 year. (Since oral tolerance is short-lived, we will permit patients in the study who have been off oral CII for \> 1 year)
• Diabetes requiring insulin or on oral medications must be well managed at baseline. Adjustment of insulin or on oral medications will be allowed during the study.
• Serum creatinine 2.0 mcg/dL.
• An 1(II) IFN value \<100% of the PBS IFN value within 1 month or less prior to the baseline and less than 25% reduction in APL A12 + 1(II) IFN from 1(II) IFN concentration.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, 38104, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Arnold E. Postlethwaite,MD Principal Investigator
• Organization: Memphis VAMC

apostlet@uthsc.edu

901 448 5774

Study Officials

• Arnold E Postlethwaite, MD

  Memphis VA Medical Center, Memphis, TN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2010
• First Posted: May 14, 2010
• Study Start: October 1, 2009
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 19, 2019
• Results First Posted: March 19, 2019

Record last verified: 2018-12

Locations

US (1)