A 12-week Dose-Ranging Trial in Patients With Moderate to Severe Plaque Psoriasis

NCT01899729 | Completed Phase 2 Results

• 2 other identifiers: 8400-2012013-000164-28
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

IMO 8400 is a second-generation oligonucleotide antagonist of endosomal Toll-like receptors (TLR) 7, TLR8 and TLR9. These TLR react to complexes of exogenous nucleic acids (as might be encountered during infection) and endogenous nucleic acids (as might be released during tissue damage during autoimmune disease). In vitro and in multiple animal models of autoimmune disease, IMO-8400 blocks immune activation mediated through TLR7, 8 and 9. In Phase 1 studies (Protocol 8400-001) IMO 8400 has been administered to healthy adults by SC injection at single-doses and multiple-doses (4 weeks) up to 0.6 mg/kg. All treatments were well-tolerated, with mild injection site reactions and no pattern of systemic reactions or laboratory changes. The current study represents the first clinical trial of IMO-8400 in patients with active autoimmune disease. Moderate to severe plaque psoriasis was chosen for this 12-week proof of activity trial based on a prior 4-week study using a first generation TLR7 and 9 antagonist which demonstrated clinical improvement in this patient population.

Conditions

Plaque Psoriasis

Keywords

plaque psoriasis; autoimmune disease; Toll like receptor

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of IMO-8400 Compared With Placebo

  The number of adverse events related and not related to treatment

  19 weeks (12 weeks on treatment + 7 week follow up)

Study Arms (5)

IMO-8400 Regimen 1

EXPERIMENTAL

IMO 8400 at 0.075 mg/kq q wk x 12 wks

Drug: IMO-8400 Regimen 1

IMO-8400 Regimen 2

EXPERIMENTAL

IMO-8400 at 0.15 mg/kg q wk x 12 wks

Drug: IMO-8400 Regimen 2

IMO-8400 Regimen 3

EXPERIMENTAL

IMO\_8400 at 0.3 mg/kg q wk x 12 wks

Drug: IMO-8400 Regimen 3

Placebo

PLACEBO COMPARATOR

Saline (placebo) q wk x 12 wks

Drug: Saline Placebo

IMO-8400 Regimen 4

EXPERIMENTAL

IMO\_8400 at 0.6 mg/kg q wk x 12 wks

Drug: IMO-8400 Regimen 4

Interventions

IMO-8400 Regimen 1 DRUG

IMO-8400 0.075 mg/kg q wk x 12 wk by subcutaneous injection

IMO-8400 Regimen 1

IMO-8400 Regimen 2 DRUG

IMO-8400 0.15 mg/kg q wk x 12 wk by subcutaneous injection

IMO-8400 Regimen 2

IMO-8400 Regimen 3 DRUG

IMO-8400 0.3 mg/kg q wk x 12 wk by subcutaneous injection

IMO-8400 Regimen 3

Saline Placebo DRUG

Saline q wk x 12 wk by subcutaneous injection

Placebo

IMO-8400 Regimen 4 DRUG

IMO-8400 0.6 mg/kg q wk x 12 wk by subcutaneous injection

IMO-8400 Regimen 4

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is age 18 to 70 years, inclusive
• Completes the informed consent procedure (see Section 15.2), including signing and dating the informed consent form
• Has moderate to severe plaque psoriasis meeting the criteria specified above
• Is willing and able to comply with the restrictions detailed above
• Female subjects must have a negative pregnancy test at screening and on Day 1 prior to start of treatment
• Female subjects of childbearing potential (see Section 8.2) and male subjects who have partners of childbearing potential must agree to use effective birth control (contraception; see Section 8.2) from Screening through the treatment period and for ninety (90) days after the last injection of study drug

You may not qualify if:

• Has known hypersensitivity to any oligodeoxynucleotide
• Is nursing
• Has body weight \<50 kg
• Has BMI \>34.9 kg/m2
• Regularly consumes \>3 drinks of alcoholic beverages (beer, wine, or distilled spirits) per day
• Has a positive test for antibody to human immunodeficiency virus (HIV-1 or -2) or hepatitis C virus (HCV)
• Has a positive test for hepatitis B surface antigen (HBsAg)
• Has at screening safety laboratory tests meeting one or more of the following criteria:
• hemoglobin \<6.52 mmol/L (\<10.5 g/dL)
• white blood cell count \<4x109/L ( \<4,000/mm3)
• absolute neutrophil count (ANC) \<1.5x109/L (\<1500/mm3)
• platelet count \<100x109/L (\<100,000/mm3 )
• serum creatinine \>1.3x ULN;
• alanine transaminase (ALT; SGPT) \>2.5x ULN
• aspartate transaminase (AST; SGOT) \>2.5x ULN

Sponsors & Collaborators

• Idera Pharmaceuticals, Inc.: lead

Study Sites (1)

Centre for Human Drug Research

Leiden, Netherlands

Location

Related Publications (1)

• Balak DM, van Doorn MB, Arbeit RD, Rijneveld R, Klaassen E, Sullivan T, Brevard J, Thio HB, Prens EP, Burggraaf J, Rissmann R. IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis. Clin Immunol. 2017 Jan;174:63-72. doi: 10.1016/j.clim.2016.09.015. Epub 2016 Nov 20.

  PMID: 27876460 DERIVED

MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Results Point of Contact

• Title: Idera Medical Monitor
• Organization: Idera Pharmaceuticals, Inc.

clinicaltrials@iderapharma.com

617-679-5500

Study Officials

• Koos J Burggraaf, MSc, MD, PhD

  Center Human Drug Research, Leiden, Netherlands

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 15, 2013
• Study Start: May 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 7, 2022
• Results First Posted: August 2, 2019

Record last verified: 2022-02

Locations

NL (1)