Once-Weekly Oral Aminopterin for the Treatment of Subjects With Moderate-To-Severe Psoriasis

NCT03431974 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: AMT-PSO-2015U44AI114473
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

This study evaluates the treatment of psoriasis with aminopterin. Participants will be treated for 14 weeks with either aminopterin or placebo followed. The participants will not know if they are being treated with aminopterin or placebo.

Conditions

Psoriasis

Keywords

Anti-folate

Outcome Measures

Primary Outcomes (2)

• Subjects With >=75% Reduction in Baseline Psoriasis Area and Severity Index (PASI) (Efficacy)

  As follows: 1. Area of Involvement. Determine a score, from 0 to 6, for each body section (head, trunk, upper limbs, lower limbs) based on the percent of psoriasis skin involvement: 0=0%, 1=\<10%, 2=10% to \<30%, 3=30% to \<50%, 4=50% to \<70%, 5=70% to \<90%, 6=90% to 100%. 2. Severity of Involvement. Determine a score, from 0 to 4, for each body section (head, trunk, upper limbs, lower limbs), for the psoriatic skin severity of each of erythema, thickness, and scaling: 0=none, 1=slight, 2=moderate, 3=severe, 4=very severe. For each body section the three severity scores are summed. 3. For each body section the product of the Area and Severity is determined. 4. For each body section the product of line 3 is multiplied by an Area Factor (head=0.1, trunk=0.3, upper limbs=0.2, lower limbs=0.4). 5. A PASI score is determined by summing the 4 body section products (line 4). The highest possible score=72; the lowest possible score=0. The higher the scores, the worse the psoriasis.

  98 days.

• Success (Score of 0 or 1) in Static Physician Global Assessment (sPGA) (Efficacy)

  As follows: 1. Induration. A score, from 0 to 5, based on: 0=No plaque elevation; 1= Minimal plaque elevation=0.25 mm; 2=Mild plaque elevation=0.5 mm; 3=Moderate plaque elevation=0.75 mm; 4=Marked plaque elevation=1.0 mm; 5=Severe plaque elevation\>1.25 mm. 2. Erythema. A score, from 0 to 5, based on: 0=No erythema, hyperpigmentation may be present; 1=Faint erythema; 2=Light red coloration; 3=Moderate red coloration; 4=Bright red coloration; 5=Dusky to deep red coloration. 3. Scaling. A score, from 0 to 5, based on: 0= No scaling; 1=Minimal; occasional fine scale on\<5% of the lesion; 2=Mild; fine scale predominates; 3=Moderate; coarse scale predominates; 4=Marked; thick, non-tenacious scale predominates; 5=Severe; very thick, tenacious scale predominates. 4. The sPGA: Induration, Erythema, and Scaling scores are rounded to the nearest whole number and averaged. 0=Cleared; 1=Minimal; 2=Mild; 3=Moderate; 4=Marked; 5=Severe. Higher score indicates worse psoriasis.

  98 days.

Study Arms (2)

LD-Aminopterin oral capsule

EXPERIMENTAL

LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses).

Drug: LD-Aminopterin oral capsule

Placebo oral capsule

PLACEBO COMPARATOR

Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses).

Drug: Placebo oral capsule

Interventions

LD-Aminopterin oral capsule DRUG

anti-folate treatment

Also known as: racemic 4-Aminopteroylglutamic acid, racemic 4-Aminofolic acid

LD-Aminopterin oral capsule

Placebo oral capsule DRUG

Microcrystalline filled capsule to mimic capsule containing aminopterin tablets

Also known as: Placebo (for aminopterin)

Placebo oral capsule

Eligibility Criteria

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

You may qualify if:

• Be 18 years of age or older.
• Have a diagnosis of moderate-to-severe psoriasis for at least 6 months confirmed by a dermatologist, defined here as plaque-type psoriasis affecting a body surface area of \>10% and a PASI of \>10.
• Agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study.
• Ability to understand and sign written informed consent.
• Heterosexually active men and women of childbearing potential must use two methods of contraception during the study (20 weeks) and for 90 days after study completion. The two methods of birth control may be used simultaneously in the same subject or simultaneously in both partners. The two birth control methods can be (a) 2 barrier methods or (b) a barrier method plus a hormonal method to prevent pregnancy.
• Barrier methods include: condom (female or male), copper intrauterine device, sponge, or spermicide.
• Hormonal Methods include: any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent, including oral, subcutaneous, intrauterine, or intramuscular agents.
• For pre-menopausal women, a negative pregnancy test, obtained within 1 week prior to first study drug dose and at study visits Week 0, Week 6, Week10, Week 14, and Week 20. If at any visit during the Treatment Phase (see Appendix A) a positive pregnancy test is returned, the subject will be discontinued from any further study drug.
• Negative serology for human immunodeficiency virus 1 and 2 (HIV1/2), hepatitis B and hepatitis C.
• The following screening laboratory blood tests must have the following values, or not clinically significant as determined by the PI and Medical Monitor: white blood cells (WBC) within normal limits (WNL); absolute neutrophil count \> lower limit of normal; platelet count WNL; hemoglobin \>10.0 g/dL; aspartate aminotransferase (AST) \< 2.5 x the upper limit of normal.
• Adequate renal function: creatinine clearance estimated by Cockcroft-Gault formula \>60 ml/min

You may not qualify if:

• Known history of hepatitis, HIV infection, interstitial lung disease.
• Greater than moderate alcohol consumption on a regular basis (moderate consumption for females is 1 drink or 1 glass of wine a day; for males is 2 drinks or 2 glasses of wine a day) and unwilling, or unable, to control consumption during the study period.
• Prior use of aminopterin (AMT).
• Use of these biologic treatments in the time frames specified:
• Within 9 months of first study drug dose: ustekinumab (Stelara).
• Within 12 weeks of first study drug dose: any experimental therapy for psoriasis or rheumatoid arthritis.
• Within 8 weeks of first study drug dose: infliximab (Remicade), adalimumab (Humira).
• Within 4 weeks of first study drug dose: etanercept (Enbrel).
• Other biologic therapies will have discontinuation periods determined by 5x their half-life.
• Within 90 days prior to Day 0 and at any time while on study, the use of MTX.
• Within 4 weeks prior to randomization and at any time while on study, use of phototherapy (e.g., ultraviolet B (UVB), narrow band UVB, Goeckerman regimen, Ingram regimen, PUVA), systemic medications (e.g. acitretin, mycophenolate mofetil, tacrolimus/FK506, cyclosporine A, azathioprine, 6-thioguanine, sulfasalazine, hydroxyurea, calcitriol, any systemic immunosuppressants), lithium, or any treatments that could affect psoriasis or sPGA evaluations. Subjects are eligible 4 weeks after the last dose of any of the aforementioned treatments was received.
• Within 2 weeks prior to randomization and at any time while on study, use of any topical medications or treatments that could affect psoriasis evaluations (e.g., corticosteroids, anthralin, vitamin D3/calcitriol and analogues such calcipotriene and tacalcitol, synthetic retinoids such as tazarotene, coal tar, and keratolytics such as salicylic acid, lactic acid and urea including those contained in over-the-counter medicated shampoos). Subjects are eligible 2 weeks after the last dose of any of the aforementioned treatments was received.
• Note: Over-the-counter topical steroids will be permitted for use limited to the face, axilla, and/or genitalia, as needed. These topical medications should not be used within approximately 24 hours prior to study visits Day 0 and Day 98. Over-the-counter shampoos for the treatment of psoriasis of the scalp are also permitted.
• Use of emollients on the morning of the first (Week 0) study visit.
• Within 2 weeks prior to Study Day 0, or on Study Day 0, or at any time during the study, use of any of the following medications that may result in drug/drug interactions with AMT: trimethoprim with or without sulfamethoxazole; sulfonamides; sulfonylureas; pyrimethamine; tromethamine; salicylates; non-steroidal anti-inflammatory (NSAID) drugs including ibuprofen; dipyridamole; colchicine; probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e., leucovorin).

Sponsors & Collaborators

• Syntrix Biosystems, Inc.: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (3)

Spectrum Dermatology

Scottsdale, Arizona, 85258, United States

Location

Dermatology Associates of Seattle

Seattle, Washington, 98101, United States

Location

Premier Clinical Research

Spokane, Washington, 99202, United States

Location

Related Publications (1)

• Menter A, Thrash B, Cherian C, Matherly LH, Wang L, Gangjee A, Morgan JR, Maeda DY, Schuler AD, Kahn SJ, Zebala JA. Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter. J Pharmacol Exp Ther. 2012 Sep;342(3):696-708. doi: 10.1124/jpet.112.195479. Epub 2012 May 31.

  PMID: 22653877 RESULT

MeSH Terms

Conditions

Psoriasis

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Aaron Schuler
• Organization: Syntrix Pharmaceuticals

aschuler@syntrixbio.com

253-833-8009

Study Officials

• Stuart Kahn, MD

  Syntrix Biosystems

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Over-encapsulated
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 13, 2018
• Study Start: November 1, 2018
• Primary Completion: January 11, 2021
• Study Completion: January 11, 2021
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)