Trial Outcomes & Findings for Once-Weekly Oral Aminopterin for the Treatment of Subjects With Moderate-To-Severe Psoriasis (NCT NCT03431974)

NCT ID: NCT03431974

Last Updated: 2023-04-14

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 19 participants
• Primary outcome timeframe: 98 days.
• Results posted on: 2023-04-14

Participant Flow

Participant milestones

Measure	LD-Aminopterin Oral Capsule LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses). LD-Aminopterin oral capsule: anti-folate treatment	Placebo Oral Capsule Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses). Placebo oral capsule: Microcrystalline filled capsule to mimic capsule containing aminopterin tablets
Overall Study STARTED	11	8
Overall Study COMPLETED	8	6
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	LD-Aminopterin Oral Capsule n=11 Participants LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses). LD-Aminopterin oral capsule: anti-folate treatment	Placebo Oral Capsule n=8 Participants Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses). Placebo oral capsule: Microcrystalline filled capsule to mimic capsule containing aminopterin tablets	Total n=19 Participants Total of all reporting groups
Age, Continuous	50.0 years STANDARD_DEVIATION 10.3 • n=5 Participants	50.0 years STANDARD_DEVIATION 13.1 • n=7 Participants	50.0 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	8 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: 98 days.

Population: Intent to treat population

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.

Outcome measures

Measure	LD-Aminopterin Oral Capsule n=11 Participants LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses). LD-Aminopterin oral capsule: anti-folate treatment	Placebo Oral Capsule n=8 Participants Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses). Placebo oral capsule: Microcrystalline filled capsule to mimic capsule containing aminopterin tablets
Subjects With >=75% Reduction in Baseline Psoriasis Area and Severity Index (PASI) (Efficacy)	3 Participants	1 Participants

PRIMARY outcome

Timeframe: 98 days.

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.

Outcome measures

Measure	LD-Aminopterin Oral Capsule n=11 Participants LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses). LD-Aminopterin oral capsule: anti-folate treatment	Placebo Oral Capsule n=8 Participants Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses). Placebo oral capsule: Microcrystalline filled capsule to mimic capsule containing aminopterin tablets
Success (Score of 0 or 1) in Static Physician Global Assessment (sPGA) (Efficacy)	1 Participants	1 Participants

Adverse Events

LD-Aminopterin Oral Capsule

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo Oral Capsule

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	LD-Aminopterin Oral Capsule n=11 participants at risk LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses). LD-Aminopterin oral capsule: anti-folate treatment	Placebo Oral Capsule n=8 participants at risk Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses). Placebo oral capsule: Microcrystalline filled capsule to mimic capsule containing aminopterin tablets
Immune system disorders Allergic reaction	9.1% 1/11 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)	0.00% 0/8 • 98 days will on treatment and 42 days afterward (140 days total)

Other adverse events

Measure	LD-Aminopterin Oral Capsule n=11 participants at risk LD-Aminopterin tablets (0.5 mg tablet) over-encapsulated, 3.0 mg (6 tablets) once orally each week for 14 weeks (14 doses). LD-Aminopterin oral capsule: anti-folate treatment	Placebo Oral Capsule n=8 participants at risk Placebo capsules containing microcrystalline once orally each week for 14 weeks (14 doses). Placebo oral capsule: Microcrystalline filled capsule to mimic capsule containing aminopterin tablets
Gastrointestinal disorders Nausea	0.00% 0/11 • 98 days will on treatment and 42 days afterward (140 days total)	12.5% 1/8 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)
Gastrointestinal disorders Diarrhea	0.00% 0/11 • 98 days will on treatment and 42 days afterward (140 days total)	12.5% 1/8 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)
Gastrointestinal disorders Abdominal pain	9.1% 1/11 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)	0.00% 0/8 • 98 days will on treatment and 42 days afterward (140 days total)
Gastrointestinal disorders Tooth pain	9.1% 1/11 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)	0.00% 0/8 • 98 days will on treatment and 42 days afterward (140 days total)
Infections and infestations Sinusitis	0.00% 0/11 • 98 days will on treatment and 42 days afterward (140 days total)	12.5% 1/8 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)
Infections and infestations Pharyngitis	9.1% 1/11 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)	0.00% 0/8 • 98 days will on treatment and 42 days afterward (140 days total)
Nervous system disorders Dizziness	0.00% 0/11 • 98 days will on treatment and 42 days afterward (140 days total)	12.5% 1/8 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)
Nervous system disorders Headache	9.1% 1/11 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)	0.00% 0/8 • 98 days will on treatment and 42 days afterward (140 days total)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/11 • 98 days will on treatment and 42 days afterward (140 days total)	12.5% 1/8 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)
General disorders Peripheral swelling	0.00% 0/11 • 98 days will on treatment and 42 days afterward (140 days total)	12.5% 1/8 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)
Immune system disorders Allergic reaction	9.1% 1/11 • Number of events 1 • 98 days will on treatment and 42 days afterward (140 days total)	0.00% 0/8 • 98 days will on treatment and 42 days afterward (140 days total)

Additional Information

Aaron Schuler

Syntrix Pharmaceuticals

Phone: 253-833-8009

Email: aschuler@syntrixbio.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor shall retain title to and the right to publish all documentation, records, raw data, specimens or other work product generated in connection with the performance of the Services. Such publications shall not be made by PI without the prior written consent of Sponsor.
• Publication restrictions are in place

Restriction type: OTHER