A Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP)

• Sponsor: Aristea Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03988335
• Collaborator: (none)
• Enrollment: 35
• Locations: 17
• Arms: 2
• Actual Duration (Months): 9.2
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis

Condition or Disease	Intervention/Treatment	Phase
Palmoplantar Pustulosis	Drug: RIST4721; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects With Palmoplantar Pustulosis
• Actual Study Start Date: Feb 13, 2019
• Actual Primary Completion Date: Nov 5, 2019
• Actual Study Completion Date: Nov 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RIST4721 RIST4721 as once-daily 300mg oral solution for 28 days.	Drug: RIST4721; RIST4721 oral solution
Placebo Comparator: Placebo Placebo as once-daily 300mg oral solution for 28 days.	Drug: Placebo; Placebo oral solution

Outcome Measures

Primary Outcome Measures

1. Log Transformed Ratio of Postbaseline Fresh Pustule Count at Day 28 to Baseline [Baseline to Day 28]

   Relative change from baseline in fresh pustule count at Day 28

2. Log Transformed Ratio of Postbaseline Total Pustule Count at Day 28 to Baseline [Baseline to Day 28]

   Relative change from baseline in total pustule count at Day 28

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least a 6-month history of PPP as defined by the presence of pustules on palms and/or soles, but without evidence of infection on palms and soles

• Moderate or severe PPP, as defined by Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) ≥8 and Palmoplantar Pustulosis Physician Global Assessment (PPPGA) ≥3 at Day -1, and a minimum of 8 fresh pustules at screening (fresh pustule count on both right/left palms and soles) and 20 fresh pustules at Day -1 (fresh pustule count on both right/left palms and soles)

• Males and females must be willing to use birth control as indicated

Exclusion Criteria:

• Moderate to severe psoriasis, as defined by plaque psoriasis covering ≥10% of total Body Surface Area (BSA) at Day -1

• Subject is known to have an immune deficiency or is immunocompromised

• Positive test for hepatitis, human immunodeficiency virus (HIV) or tuberculosis

• Use of topical therapies for PPP within 2 weeks of Day -1 and/or systemic therapies for PPP within 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kirk Barber Research	Calgary	Alberta	Canada	T2G 1B1
2	Alberta DermaSurgery Centre	Edmonton	Alberta	Canada	T6G 1C3
3	CARe Clinic (Central Alberta Research Clinic)	Red Deer	Alberta	Canada	T4N 6V7
4	Winnipeg Clinic	Winnipeg	Manitoba	Canada	R3C 0N2
5	Brunswick Dermatology Center	Fredericton	New Brunswick	Canada	E3B 1G9
6	SimcoDerm Medical and Surgical Dermatology Center	Barrie	Ontario	Canada	L4M 7G1
7	Lynderm Research Inc.	Markham	Ontario	Canada	L3P 1X2
8	North Bay Dermatology Centre	North Bay	Ontario	Canada	P1B 3Z7
9	York Dermatology Center	Richmond Hill	Ontario	Canada	L4C 9M7
10	Dr. Lyne Giroux Medicine Professional Corporation	Sudbury	Ontario	Canada	P3A 1W8
11	Innovaderm Research Inc.	Montréal	Quebec	Canada	H2X 2V1
12	Dre Angelique Gagne-Henley MD Inc.	St-Jérôme	Quebec	Canada	J7Z 3B8
13	Fachklinik Bad Bentheim	Bad Bentheim		Germany	48455
14	Rothhaar Studien GmbH	Berlin		Germany	10783
15	Hautarztpraxis Dr. Niesmann & Dr. Othlinghaus	Bochum		Germany	44793
16	MensingDerma research GmbH	Hamburg		Germany	22391
17	Hautarztpraxis Dr. Wilfried Steinborn	Straubing		Germany	94315

Sponsors and Collaborators

• Aristea Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 22, 2019
• Statistical Analysis Plan - Dec 20, 2019

More Information

Additional Information:

• A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis

Publications

None provided.

• Responsible Party: Aristea Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03988335
• Other Study ID Numbers: RIST4721-201
• First Posted: Jun 17, 2019
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aristea Therapeutics, Inc.: PPP
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Pre-assignment Detail	Subjects must have at least a 6-month history of PPP and have moderate or severe PPP.

Arm/Group Title	RIST4721	Placebo
Arm/Group Description	Subjects were randomized to receive RIST4721 300 mg oral solution once daily for 28 days.	Subjects were randomized to receive Placebo oral solution once daily for 28 days.
Period Title: Overall Study
STARTED	16	19
COMPLETED	14	18
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	RIST4721	Placebo	Total
Arm/Group Description	This arm was randomized to receive 300 mg of RIST4721 once daily for 28 days.	This arm was randomized to receive placebo once daily for 28 days.	Total of all reporting groups
Overall Participants	16	19	35
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 93.8%	19 100%	34 97.1%
>=65 years	1 6.3%	0 0%	1 2.9%
Sex: Female, Male (Count of Participants)
Female	12 75%	16 84.2%	28 80%
Male	4 25%	3 15.8%	7 20%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 5.3%	1 2.9%
White	16 100%	17 89.5%	33 94.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 5.3%	1 2.9%
Region of Enrollment (participants) [Number]
Canada	11 68.8%	12 63.2%	23 65.7%
Germany	5 31.3%	7 36.8%	12 34.3%

Outcome Measures

1. Primary Outcome

Title	Log Transformed Ratio of Postbaseline Fresh Pustule Count at Day 28 to Baseline
Description	Relative change from baseline in fresh pustule count at Day 28
Time Frame	Baseline to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIST4721 300 mg	Placebo
Arm/Group Description	RIST4721 300 mg (mITT Analysis Set)	Placebo (mITT Analysis Set)
Measure Participants	14	18
Mean (Standard Deviation) [Log transformed ratio]	0.86 (0.692)	0.53 (0.561)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RIST4721 300 mg, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	The primary endpoints were first tested at alpha of 10% (2-sided). If the larger p-value was less than 10% (2-sided), both primary endpoints were to be declared statistically significant. If the larger p-value was greater than 10%, but the smaller p-value was less than 5% (2-sided), then the primary endpoint with the smaller p-value was to be declared statistically significant.
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Hochberg's method
	Comments

2. Primary Outcome

Title	Log Transformed Ratio of Postbaseline Total Pustule Count at Day 28 to Baseline
Description	Relative change from baseline in total pustule count at Day 28
Time Frame	Baseline to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RIST4721 300 mg	Placebo
Arm/Group Description	RIST4721 300 mg (mITT Analysis Set)	Placebo (mITT Analysis Set)
Measure Participants	14	18
Mean (Standard Deviation) [Log transformed ratio]	0.99 (0.667)	0.96 (0.672)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RIST4721 300 mg, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	The primary endpoints were first tested at alpha of 10% (2-sided). If the larger p-value was less than 10% (2sided), both primary endpoints were to be declared statistically significant. If the larger p-value was greater than 10%, but the smaller p-value was less than 5% (2-sided), then the primary endpoint with the smaller p-value was to be declared statistically significant.
Statistical Test of Hypothesis	p-Value	0.804
	Comments
	Method	Hochberg's method
	Comments

Adverse Events

Time Frame	From ICF signature to end of study participation (approximately 73 days)
Arm/Group Title	RIST4721 300 mg		Placebo
Arm/Group Description	All subjects who received at least one dose of RIST4721 300 mg (Safety Analysis Set).		All subjects who received at least one dose of Placebo (Safety Analysis Set).
All Cause Mortality
	RIST4721 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/19 (0%)
Serious Adverse Events
	RIST4721 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	RIST4721 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/15 (86.7%)		7/19 (36.8%)
Blood and lymphatic system disorders
Neutropenia	2/15 (13.3%)	2	0/19 (0%)	0
Leukopenia	1/15 (6.7%)	1	0/19 (0%)	0
Gastrointestinal disorders
Diarrhoea	5/15 (33.3%)	6	1/19 (5.3%)	1
Abnormal faeces	2/15 (13.3%)	2	0/19 (0%)	0
Nausea	2/15 (13.3%)	2	0/19 (0%)	0
Abdominal pain	1/15 (6.7%)	1	0/19 (0%)	0
General disorders
Fatigue	1/15 (6.7%)	1	0/19 (0%)	0
Infections and infestations
Folliculitis	2/15 (13.3%)	3	0/19 (0%)	0
Nasopharyngitis	0/15 (0%)	0	1/19 (5.3%)	1
Post procedural cellulitis	1/15 (6.7%)	1	0/19 (0%)	0
Injury, poisoning and procedural complications
Procedural pain	2/15 (13.3%)	2	1/19 (5.3%)	1
Ligament sprain	0/15 (0%)	0	1/19 (5.3%)	1
Concussion	1/15 (6.7%)	1	0/19 (0%)	0
Investigations
Bacterial test	1/15 (6.7%)	1	0/19 (0%)	0
Blood glucose increased	1/15 (6.7%)	1	0/19 (0%)	0
Blood triglycerides increased	1/15 (6.7%)	1	0/19 (0%)	0
Hepatic enzyme increased	1/15 (6.7%)	1	0/19 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/15 (6.7%)	1	0/19 (0%)	0
Increased appetite	1/15 (6.7%)	1	0/19 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	2/15 (13.3%)	2	0/19 (0%)	0
Pain in extremity	1/15 (6.7%)	1	1/19 (5.3%)	1
Myalgia	0/15 (0%)	0	1/19 (5.3%)	1
Osteoarthritis	1/15 (6.7%)	1	0/19 (0%)	0
Back pain	0/15 (0%)	0	1/19 (5.3%)	1
Nervous system disorders
Dizziness	0/15 (0%)	0	2/19 (10.5%)	2
Headache	1/15 (6.7%)	1	1/19 (5.3%)	1
Psychiatric disorders
Anxiety	1/15 (6.7%)	1	0/19 (0%)	0
Renal and urinary disorders
Urine odour abnormal	3/15 (20%)	3	0/19 (0%)	0
Micturition disorder	0/15 (0%)	0	1/19 (5.3%)	1
Reproductive system and breast disorders
Vaginal haemorrhage	0/15 (0%)	0	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/15 (6.7%)	1	0/19 (0%)	0
Skin and subcutaneous tissue disorders
Skin fissures	1/15 (6.7%)	1	0/19 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.