A Study to Assess the Efficacy and Safety of PPC-06 (Tepilamide Fumarate)

• Sponsor: Dr. Reddy's Laboratories Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03421197
• Collaborator: (none)
• Enrollment: 426
• Locations: 74
• Arms: 4
• Actual Duration (Months): 26.1
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of PPC-06 (tepilamide fumarate) extended release in subjects with moderate-to-severe plaque psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: PPC-06 400 mg QD; Drug: PPC-06 400 mg BID; Drug: PPC-06 600 mg; Drug: Placebo	Phase 2

Detailed Description

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of PPC-06 in subjects with moderate-to-severe plaque psoriasis. Study subjects will be enrolled at approximately 75 sites in the United States (US).

Approximately 400 subjects who meet the study entry criteria will be randomly assigned in a 1:1:1:1 ratio to 1 of the 4 treatment arms:

1. PPC-06 400 mg once daily (QD)

2. PPC-06 400 mg BID

3. PPC-06 600 mg BID

4. Placebo BID The maximum study duration for each subject will be approximately 29 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 426 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: RandomizedRandomized
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 24-Week Study to Assess the Efficacy and Safety of PPC-06 (Tepilamide Fumarate) Extended Release Tablets in Subjects With Moderate-to-Severe Plaque Psoriasis (AFFIRM)
• Actual Study Start Date: Jan 25, 2018
• Actual Primary Completion Date: Mar 30, 2020
• Actual Study Completion Date: Mar 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PPC-06 400 mg QD Tepilamide Fumarate 400 mg once per day	Drug: PPC-06 400 mg QD; Tepilamide Fumarate 400 mg tablet once per day; Other Names: Tepilamide Fumarate 400 mg
Experimental: PPC-06 400 mg BID Tepilamide Fumarate 400 mg twice per day	Drug: PPC-06 400 mg BID; Tepilamide Fumarate tablets 400 mg twice per day; Other Names: Tepilamide Fumarate 400 mg
Experimental: PPC-06 600 mg BID Tepilamide Fumarate 600 mg twice per day	Drug: PPC-06 600 mg; Tepilamide Fumarate tablets 600 mg twice per day; Other Names: Tepilamide Fumarate 600 mg
Placebo Comparator: Placebo BID White placebo tablet to mimic Tepilamide Fumarate	Drug: Placebo; white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets; Other Names: Placebo tablets twice per day

Outcome Measures

Primary Outcome Measures

1. Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 [End of Week 24]

   The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index (PASI-75) The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject.

2. Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 [End of Week 24]

   The Percentage of subjects who achieve the Investigator's Global Assessment (IGA) score of clear or almost clear (IGA score 0 or 1) Score Grade Definition 0 Clear: No signs of psoriasis Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques Severe: Marked thickening with hard/sharp edges; Bright to deep dark red coloration; Thick/coarse scaling covering almost all or all lesions A lower score on this scale at the end of the study indicates an improvement in the disease condition.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Generally healthy males or non-pregnant females age ≥18 years at the time of screening (or who have reached the state minimum legal age of consent).

• Stable, moderate-to-severe plaque psoriasis diagnosed for at least 6 months prior to randomization (no morphology changes or significant flares of disease activity in the last 6 months in the opinion of the investigator or as reported by the subject).

• Severity of disease meeting all 3 of the following criteria prior to randomization (at the Baseline [Day 0] visit):

1. PASI score of ≥12

2. Total body surface area (BSA) affected by plaque psoriasis of ≥10%

3. IGA score of >3

• Must be a candidate for phototherapy and/or systemic therapy for psoriasis.

Exclusion Criteria:

• Subjects with non-plaque psoriasis (ie, predominantly inverse, erythrodermic, predominantly guttate, or pustular psoriasis).

• Subjects with drug-induced psoriasis or subjects with drug-exacerbated psoriasis that has not resolved within 4 weeks prior to screening.

• Subjects who have received systemic non-biologic psoriasis therapy or phototherapy (including either oral and topical psoralen and ultraviolet A (PUVA) light therapy, ultraviolet B, or self-treatment with tanning beds or therapeutic sunbathing) within 4 weeks prior to the Baseline Visit.

• Subjects who had topical psoriasis treatment within the previous 2 weeks prior to the Baseline Visit.

• Subjects with history of concurrent or recent use of any biologic agent within the following washout periods prior to baseline visit:

• Etanercept - 35 days

• Infliximab, adalimumab - 12 weeks

• Ustekinumab - 24 weeks

• Any other biologic agent <5 half-lives prior to the Baseline Visit

• Subjects with history of use of any investigational drug within 28 days prior to randomization, or 5 pharmacokinetic/ pharmacodynamic half-lives (whichever is longer).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 144	Glendale	Arizona	United States	85308
2	Site 167	Phoenix	Arizona	United States	85018
3	Site 158	Phoenix	Arizona	United States	85053
4	Site 170	Tempe	Arizona	United States	85283
5	Site 157	Bryant	Arkansas	United States	72022
6	Site 125	Rogers	Arkansas	United States	72758
7	Site 133	Fountain Valley	California	United States	92708
8	Site 107	Fremont	California	United States	94538
9	Site 121	Fresno	California	United States	93720
10	Site 153	Fullerton	California	United States	92835
11	Site 176	Los Angeles	California	United States	90057
12	Site 178	Los Angeles	California	United States	90057
13	Site 182	Los Angeles	California	United States	90057
14	Site 156	Murrieta	California	United States	92562
15	Site 141	San Diego	California	United States	92123
16	Site 155	Santa Rosa	California	United States	95405
17	Site 137	Clearwater	Florida	United States	33761
18	Site 130	Coral Gables	Florida	United States	33134
19	Site 143	Hialeah	Florida	United States	33012
20	Site 145	Hialeah	Florida	United States	33012
21	Site 181	Hialeah	Florida	United States	33012
22	Site 149	Miami	Florida	United States	33014
23	Site 105	Miami	Florida	United States	33144
24	Site 174	Miami	Florida	United States	33155
25	Site 164	Miami	Florida	United States	33175
26	Site 123	Miami	Florida	United States	33186
27	Site 112	Miramar	Florida	United States	33027
28	Site 172	New Port Richey	Florida	United States	34655
29	Site 152	Orange Park	Florida	United States	32073
30	Site 154	Pembroke Pines	Florida	United States	33028
31	Site 110	Sweetwater	Florida	United States	33172
32	Site 150	Tampa	Florida	United States	33609
33	Site 113	Tampa	Florida	United States	33624
34	Site 132	Marietta	Georgia	United States	30060
35	Site 124	Savannah	Georgia	United States	31406
36	Site 122	Nampa	Idaho	United States	83651
37	Site 179	Wheaton	Illinois	United States	60189
38	Site 115	Indianapolis	Indiana	United States	46256
39	Site 171	New Albany	Indiana	United States	47150
40	Site 139	Overland Park	Kansas	United States	66215
41	Site 165	Louisville	Kentucky	United States	40202
42	Site 131	Louisville	Kentucky	United States	40217
43	Site 142	Louisville	Kentucky	United States	40241
44	Site 119	Baton Rouge	Louisiana	United States	70808
45	Site 126	New Orleans	Louisiana	United States	70115
46	Site 128	Clinton Township	Michigan	United States	48038
47	Site 129	Fridley	Minnesota	United States	55432
48	Site 111	Kansas City	Missouri	United States	64114
49	Site 109	Omaha	Nebraska	United States	68114
50	Site 127	Las Vegas	Nevada	United States	89119
51	Site 180-	Las Vegas	Nevada	United States	89148
52	Site 103	New York	New York	United States	10012
53	Site 177	New York	New York	United States	10075
54	Site 104	New York	New York	United States	10155
55	Site 161	Rochester	New York	United States	14623
56	Site 146	Stony Brook	New York	United States	11790
57	Site 108	High Point	North Carolina	United States	27262
58	Site 116	Wilmington	North Carolina	United States	28405
59	Site 118	Beachwood	Ohio	United States	44122
60	Site 169	Cincinnati	Ohio	United States	45236
61	Site 114	Johnston	Rhode Island	United States	02919
62	Site 134	Mount Pleasant	South Carolina	United States	29464
63	Site 100	Rapid City	South Dakota	United States	57702
64	Site 148	Austin	Texas	United States	78745
65	Site 160	Bellaire	Texas	United States	77401
66	Site 162	Houston	Texas	United States	77004
67	Site 102	Houston	Texas	United States	77056
68	Site 106	San Antonio	Texas	United States	78229
69	Site 101	San Antonio	Texas	United States	78281
70	Site 159	Sugar Land	Texas	United States	77479
71	Site 136	Orem	Utah	United States	84058
72	Site 166	Norfolk	Virginia	United States	23507
73	Site 135	Burien	Washington	United States	98168
74	Site 147	Spokane	Washington	United States	99202

Sponsors and Collaborators

• Dr. Reddy's Laboratories Limited

Investigators

• Study Director: Srinivas Sidgiddi, MD, Dr. Reddy's Laboratories, Inc

Study Documents (Full-Text)

• Study Protocol - Oct 26, 2018
• Statistical Analysis Plan - Apr 15, 2019

More Information

Publications

None provided.

• Responsible Party: Dr. Reddy's Laboratories Limited
• ClinicalTrials.gov Identifier: NCT03421197
• Other Study ID Numbers: PPC-06-CD-004
• First Posted: Feb 5, 2018
• Last Update Posted: Apr 1, 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: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Arm/Group Title	PPC-06 400 mg QD	PPC-06 400 mg BID	PPC-06 600 mg BID	Placebo BID
Arm/Group Description	Tepilamide Fumarate 400 mg once per day PPC-06 400 mg QD: Tepilamide Fumarate 400 mg tablet once per day	Tepilamide Fumarate 400 mg twice per day PPC-06 400 mg BID: Tepilamide Fumarate tablets 400 mg twice per day	Tepilamide Fumarate 600 mg twice per day PPC-06 600 mg: Tepilamide Fumarate tablets 600 mg twice per day	White placebo tablet to mimic Tepilamide Fumarate Placebo: white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets
Period Title: Overall Study
STARTED	105	107	107	107
COMPLETED	67	68	56	62
NOT COMPLETED	38	39	51	45

Baseline Characteristics

Arm/Group Title	PPC-06 400 mg QD	PPC-06 400 mg BID	PPC-06 600 mg BID	Placebo BID	Total
Arm/Group Description	Tepilamide Fumarate 400 mg once per day PPC-06 400 mg QD: Tepilamide Fumarate 400 mg tablet once per day	Tepilamide Fumarate 400 mg twice per day PPC-06 400 mg BID: Tepilamide Fumarate tablets 400 mg twice per day	Tepilamide Fumarate 600 mg twice per day PPC-06 600 mg: Tepilamide Fumarate tablets 600 mg twice per day	White placebo tablet to mimic Tepilamide Fumarate Placebo: white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets	Total of all reporting groups
Overall Participants	105	107	107	107	426
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.0 (13.18)	51.0 (12.29)	50.2 (13.74)	49.3 (12.59)	49.6 (12.96)
Sex: Female, Male (Count of Participants)
Female	40 38.1%	43 40.2%	43 40.2%	43 40.2%	169 39.7%
Male	65 61.9%	64 59.8%	64 59.8%	64 59.8%	257 60.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%	2 1.9%	0 0%	1 0.9%	4 0.9%
Asian	1 1%	3 2.8%	2 1.9%	1 0.9%	7 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.9%	0 0%	0 0%	1 0.2%
Black or African American	6 5.7%	4 3.7%	11 10.3%	5 4.7%	26 6.1%
White	97 92.4%	96 89.7%	92 86%	97 90.7%	382 89.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 0.9%	2 1.9%	3 2.8%	6 1.4%
Region of Enrollment (participants) [Number]
United States	105 100%	107 100%	107 100%	107 100%	426 100%
Psoriasis Area and Severity Index (PASI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	18.41 (6.377)	18.56 (8.004)	18.00 (6.680)	17.26 (6.169)	18.05 (6.842)

Outcome Measures

1. Primary Outcome

Title	Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24
Description	The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index (PASI-75) The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject.
Time Frame	End of Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population which included all randomized subjects who received at least one dose of IP and had at least one post-dose efficacy assessment.

Arm/Group Title	PPC-06 400 mg QD	PPC-06 400 mg BID	PPC-06 600 mg BID	Placebo BID
Arm/Group Description	Tepilamide Fumarate 400 mg once per day PPC-06 400 mg QD: Tepilamide Fumarate 400 mg tablet once per day	Tepilamide Fumarate 400 mg twice per day PPC-06 400 mg BID: Tepilamide Fumarate tablets 400 mg twice per day	Tepilamide Fumarate 600 mg twice per day PPC-06 600 mg: Tepilamide Fumarate tablets 600 mg twice per day	White placebo tablet to mimic Tepilamide Fumarate Placebo: white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets
Measure Participants	101	102	101	102
Number [percentage of total participants]	39.7 37.8%	47.2 44.1%	44.3 41.4%	20.0 18.7%

2. Primary Outcome

Title	Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1
Description	The Percentage of subjects who achieve the Investigator's Global Assessment (IGA) score of clear or almost clear (IGA score 0 or 1) Score Grade Definition 0 Clear: No signs of psoriasis Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques Severe: Marked thickening with hard/sharp edges; Bright to deep dark red coloration; Thick/coarse scaling covering almost all or all lesions A lower score on this scale at the end of the study indicates an improvement in the disease condition.
Time Frame	End of Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population included all randomized subjects who received at least one dose of IP and had at least one post-dose efficacy assessment.

Arm/Group Title	PPC-06 400 mg QD	PPC-06 400 mg BID	PPC-06 600 mg BID	Placebo BID
Arm/Group Description	Tepilamide Fumarate 400 mg once per day PPC-06 400 mg QD: Tepilamide Fumarate 400 mg tablet once per day	Tepilamide Fumarate 400 mg twice per day PPC-06 400 mg BID: Tepilamide Fumarate tablets 400 mg twice per day	Tepilamide Fumarate 600 mg twice per day PPC-06 600 mg: Tepilamide Fumarate tablets 600 mg twice per day	White placebo tablet to mimic Tepilamide Fumarate Placebo: white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets
Measure Participants	101	102	101	102
Number [percentage of total participants]	35.7 34%	41.4 38.7%	44.4 41.5%	22.0 20.6%

Adverse Events

Time Frame	Adverse events were collected from the time of signing the informed consent, up to 30 days after the last dose.
Adverse Event Reporting Description	Adverse events were assessed at all study visits. Adverse events were monitored by the investigator from the time of signing informed consent, up to 30 days after the subject has stopped study treatment or until the AE had resolved or stabilized. Adverse events were evaluated in the Safety Population.
Arm/Group Title	PPC-06 400 mg QD		PPC-06 400 mg BID		PPC-06 600 mg BID		Placebo BID
Arm/Group Description	Tepilamide Fumarate 400 mg once per day PPC-06 400 mg QD: Tepilamide Fumarate 400 mg tablet once per day		Tepilamide Fumarate 400 mg twice per day PPC-06 400 mg BID: Tepilamide Fumarate tablets 400 mg twice per day		Tepilamide Fumarate 600 mg twice per day PPC-06 600 mg: Tepilamide Fumarate tablets 600 mg twice per day		White placebo tablet to mimic Tepilamide Fumarate Placebo: white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets
All Cause Mortality
	PPC-06 400 mg QD		PPC-06 400 mg BID		PPC-06 600 mg BID		Placebo BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/105 (0%)		0/107 (0%)		0/106 (0%)		0/107 (0%)
Serious Adverse Events
	PPC-06 400 mg QD		PPC-06 400 mg BID		PPC-06 600 mg BID		Placebo BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/105 (2.9%)		3/107 (2.8%)		0/106 (0%)		2/107 (1.9%)
Gastrointestinal disorders
Diverticulitis	1/105 (1%)	1	0/107 (0%)	0	0/106 (0%)	0	0/107 (0%)	0
Immune system disorders
Hypersensitivity	0/105 (0%)	0	1/107 (0.9%)	1	0/106 (0%)	0	0/107 (0%)	0
Infections and infestations
Diverticulitis	1/105 (1%)	1	0/107 (0%)	0	0/106 (0%)	0	0/107 (0%)	0
Staphylococcal skin infection	0/105 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	1/107 (0.9%)	1
Injury, poisoning and procedural complications
Femur fracture	0/105 (0%)	0	1/107 (0.9%)	1	0/106 (0%)	0	0/107 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	0/105 (0%)	0	1/107 (0.9%)	1	0/106 (0%)	0	0/107 (0%)	0
Nervous system disorders
Cervical cord compression	0/105 (0%)	0	0/107 (0%)	0	0/106 (0%)	0	1/107 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea/Shortness of Breath	1/105 (1%)	1	0/107 (0%)	0	0/106 (0%)	0	0/107 (0%)	0
Other (Not Including Serious) Adverse Events
	PPC-06 400 mg QD		PPC-06 400 mg BID		PPC-06 600 mg BID		Placebo BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/105 (28.6%)		42/107 (39.3%)		68/106 (64.2%)		9/107 (8.4%)
Blood and lymphatic system disorders
Lymphopenia	4/105 (3.8%)	4	4/107 (3.7%)	5	10/106 (9.4%)	10	0/107 (0%)	0
Eosinophilia	5/105 (4.8%)	5	6/107 (5.6%)	7	5/106 (4.7%)	5	0/107 (0%)	0
Gastrointestinal disorders
Diarrhea	7/105 (6.7%)	12	19/107 (17.8%)	20	24/106 (22.6%)	32	5/107 (4.7%)	5
Nausea	7/105 (6.7%)	8	7/107 (6.5%)	7	11/106 (10.4%)	11	2/107 (1.9%)	2
Abdominal Pain	4/105 (3.8%)	4	5/107 (4.7%)	6	12/106 (11.3%)	13	0/107 (0%)	0
Infections and infestations
Urinary Tract Infection	3/105 (2.9%)	3	1/107 (0.9%)	1	6/106 (5.7%)	7	2/107 (1.9%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.