A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial to Establish the Efficacy and Safety of Once-Weekly Oral Aminopterin for the Treatment of Subjects With Moderate-To-Severe Psoriasis

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



Sponsors


Source

Syntrix Biosystems, Inc.

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

No


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.

Detailed Description

A Phase 2, multi-center, randomized, double-blind, placebo-controlled study enrolling
subjects with moderate-to-severe psoriasis to investigate the safety and efficacy of
LD-aminopterin (AMT) (3 mg (six 0.5 mg tablets). Forty-six subjects will be randomized to one
of two parallel treatment arms: LD-AMT (3 mg) or placebo, in a 1:1 ratio. The endpoint
analysis will include efficacy and safety. Randomized subjects will initially enter a 14-week
treatment phase, followed by a 6-week post-treatment phase.

Overall Status

Not yet recruiting

Start Date

2018-05-01

Completion Date

2020-10-01

Primary Completion Date

2020-04-01

Phase

Phase 2

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Psoriasis Area and Severity Index (PASI) (Efficacy)
98 days.
Static Physician Global Assessment (sPGA) (Efficacy)
98 days.
Analysis of Treatment Emergent Adverse Events
140 days.

Enrollment

46

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

anti-folate treatment

Arm Group Label

Aminopterin oral capsule


Intervention Type

Drug

Intervention Name


Description

Microcrystalline filled capsule to mimic capsule containing aminopterin tablets

Arm Group Label

Placebo oral capsule

Other Name

Placebo (for aminopterin)



Eligibility

Criteria

Inclusion Criteria:

1. Be 18 years of age or older.

2. 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.

3. Agree to avoid prolonged sun exposure and avoid use of tanning booths or other
ultraviolet light sources during the study.

4. Ability to understand and sign written informed consent.

5. 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.

6. 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.

7. Negative serology for human immunodeficiency virus 1 and 2 (HIV1/2), hepatitis B and
hepatitis C.

8. 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.

9. Adequate renal function: glomerular filtration rate (GFR) estimated by Cockcroft-Gault
formula >60 ml/min

Exclusion Criteria:

1. Known history of hepatitis, HIV infection, interstitial lung disease.

2. 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.

3. Prior use of methotrexate (MTX) or aminopterin (AMT).

4. 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.

5. 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-thiogaunine, sulfasalazine,
hydroyurea, 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.

6. 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.

7. Use of emollients on the morning of the first (Week 0) study visit.

8. 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; triamethamine; salicylates; non-steroidal
anti-inflammatory (NSAID) drugs including ibuprofen; dipyridamole; colchicine;
probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e.,
leucovorin).

9. Known concurrent malignancy except basal or squamous cell skin carcinoma, or cervical
carcinoma in situ.

10. Concurrent participation in another clinical trial involving experimental treatment
within 30 days of Study Day 0.

11. Current and uncontrolled infection, cardiovascular, renal, pulmonary, hepatic or GI
conditions that will interfere with the conduct of the trial or pose a morbid risk.

12. Investigator's opinion that a concurrent disease or condition impairs the subject's
ability to complete the trial: includes psychological, familial, sociological,
geographical or medical conditions.

13. Breast-feeding.

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Stuart Kahn, MD
Study Director
Syntrix Biosystems

Overall Contact

Last Name

Stuart Kahn, MD

Phone

253-833-8009

Phone Ext

31

Email



Verification Date

2018-02-01

Lastchanged Date

2018-02-12

Firstreceived Date

2018-02-01

Responsible Party

Responsible Party Type

Sponsor


Keyword


Has Expanded Access

No

Condition Browse


Secondary Id

5U44AI114473

Number Of Arms

2

Intervention Browse

Mesh Term

Aminopterin


Arm Group

Arm Group Label

Aminopterin oral capsule

Arm Group Type

Experimental

Description

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


Arm Group Label

Placebo oral capsule

Arm Group Type

Placebo Comparator

Description

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



Results Reference

Citation

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


Firstreceived Results Date

N/A

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

Over-encapsulated


Study First Submitted

February 1, 2018

Study First Submitted Qc

February 6, 2018

Study First Posted

February 13, 2018

Last Update Submitted

February 12, 2018

Last Update Submitted Qc

February 12, 2018

Last Update Posted

February 14, 2018


ClinicalTrials.gov processed this data on February 14, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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