Clinical Trials Register

Summary
EudraCT Number:	2015-004274-15
Sponsor's Protocol Code Number:	Pelle-926-201
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2015-004274-15

A.3

Full title of the trial

Double-Blind, Randomized, Vehicle-Controlled Proof of Concept Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Proof of Concept Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients

A.4.1

Sponsor's protocol code number

Pelle-926-201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PellePharm, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	PellePharm, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PellePharm, Inc
B.5.2	Functional name of contact point	Karl R. Beutner
B.5.3	Address:
B.5.3.1	Street Address	275 Middlefield Rd., Suite 100
B.5.3.2	Town/ city	Menlo Park, CA
B.5.3.4	Country	United States
B.5.4	Telephone number	707592 9915
B.5.6	E-mail	kbeutner@pellepharm.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Patidegib 2%
D.3.4	Pharmaceutical form	Gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Patidegib
D.3.9.1	CAS number	1169829-40-6
D.3.9.2	Current sponsor code	Patidegib
D.3.9.3	Other descriptive name	N-((2S,3R,3aS,3'R,4a'R,6S,6a'R,6b'S,7aR,12a'S,12b'S,Z)-3,6,11',12b'-tetramethyl-2',3a,3',4,4',4a',5,5',6,6',6a',6b',7,7a,7',8',10',12',12a',12b'-icosahydro-1'H,3H-spiro[furo[3,2-b]pyridine-2,9'-naphtho[2,1-a]azulene]-3'-yl)methanesulfonamide hydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Patidegib 4%
D.3.4	Pharmaceutical form	Gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Patidegib
D.3.9.1	CAS number	1169829-40-6
D.3.9.2	Current sponsor code	Patidegib
D.3.9.3	Other descriptive name	N-((2S,3R,3aS,3'R,4a'R,6S,6a'R,6b'S,7aR,12a'S,12b'S,Z)-3,6,11',12b'-tetramethyl-2',3a,3',4,4',4a',5,5',6,6',6a',6b',7,7a,7',8',10',12',12a',12b'-icosahydro-1'H,3H-spiro[furo[3,2-b]pyridine-2,9'-naphtho[2,1-a]azulene]-3'-yl)methanesulfonamide hydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Gel
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Basal Cell Nevus Syndrome

E.1.1.1

Medical condition in easily understood language

Basal Cell Nevus Syndrome

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10004151
E.1.2	Term	Basal cell nevus syndrome
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. Clinical efficacy of patidegib as defined by the percent decrease in greatest diameter of baseline treatment targeted Surgically Eligible basal cell carcinomas (SEBs) after 26 weeks of treatment [SEBs are defined as clinically diagnosed basal cell carcinoma (BCC) 5 mm or greater in diameter on the face excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face].
2. Molecular efficacy of treatment as defined by reduction in the hedgehog (HH) signaling pathway after treatment with patidegib gel 2% or 4% or vehicle applied twice daily for 6 weeks to treatment-targeted SEBs.
3. Safety and tolerability of treatment with patidegib gel 2% or 4% or vehicle applied twice daily for 26 weeks.

E.2.2

Secondary objectives of the trial

1. Clinical efficacy of treatment as defined by percent decrease in greatest diameter of baseline central facial SEBs (BCCs 3mm or greater in diameter at Baseline located on the nose or periorbital area).
2. Frequency of new SEBs on the face. (A new SEB is defined as a SEB first noted at a visit after Week 2 and that developed at a site where there was no visible BCC of any size at the Baseline or the Wk 2 visit.)
3. Proportion of non-central facial BCCs that at Baseline and/or Wk 2 visit were less than 5 mm in greatest diameter but by the Week 6, 10, 14, 18, 22, or 26 visit have become greater than 5 mm in greatest diameter.
4. Proportion of baseline treatment targeted SEBs that at the end of 26 wks of treatment are no longer large enough to be classified as SEBs (i.e., that is the proportion of baseline treatment targeted SEBs on the face that become less than 5mm in greatest diameter and non-facial baseline treatment targeted SEBs that become less than 9 mm in greatest diameter).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-The subject is from 18 to 85 years of age, inclusive.
- The subject must meet diagnostic criteria for basal cell nevus syndrome (BCNS) including major criterion #3a plus one additional major criterion or major criterion #3a plus two of the minor criteria outlined below:
Major Criteria:
a. More than 2 histologically confirmed BCCs or one under the age of 20 years
b. Odontogenic keratocysts of the jaw proven by histology
c. Three or more palmar and/or plantar pits
d. Bilamellar calcification of the falx cerebri (if less than 20 years old)
e. Fused, bifid, or markedly splayed ribs.
f. First degree relative with basal cell nevus syndrome (BCNS)
g. PTCH1 gene mutation in normal tissue
Minor Criteria
a. Macrocephaly
b. Congenital malformations: cleft lip or palate, frontal bossing, “coarse face”, moderate or severe hypertelorism
c. Skeletal abnormalities: sprengel deformity, marked pectus deformity, or marked syndactyly of the digits
d. Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defects of the hands and feet, or flame shaped lucencies of the hands or feet
e. Ovarian fibroma
f. Medulloblastoma

- The subject must have a history of at least 10 BCC in toto present at baseline and/or treated within 24 months prior to screening.
- The subject has at baseline, a total of at least 5 previously untreated SEBs (greatest diameter 5 mm or greater on the face excluding the nose and periorbital skin, 9 mm or greater on non-facial areas excluding the skin below the knees), as documented clinically by the Investigator at Baseline. Untreated is define as no previous surgical or topical or intralesional drug treatment. Previous treatment with systemically administered drugs more than 6 months prior to baseline is not considered previous treatment as long as there was no clinical evidence of resistance to oral HH (e.g., vismodegib, patidegib, and sonidegib) inhibitors. Baseline treatment targeted SEBs must not exceed a diameter of >2cm. At least one of these tumors must be appropriate for a 2 mm punch biopsy for biomarker analysis and Baseline and Week 6 visits. If a subject has 5 or more facial, excluding periorbital and nasal skin, SEBs at baseline, non-facial SEBs will not be treatment targeted SEBs.

E.4

Principal exclusion criteria

- The subject is a woman of childbearing potential. This proscription is based on the key role of the HH pathway in embryogenesis, the known preclinical teratogenic effects of systemic cyclopamine, a naturally occurring inhibitor of SMO, and the unknown level of systemic exposure following topical application of patidegib in humans. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months.
- The subject has used topical facial products or within 5 cm of a treatment targeted SEB or systemic therapies that might interfere with the evaluation of the study medication during the study. Specifically these include the use of:
a. Topical glucocorticoids 30 days prior to screening
b. Retinoids (e.g., etretinate, isotretinoin, tazarotene, tretinoin, adaplalene) systemically or topically or > 5% of an alphahydroxy acid (e.g., glycolic acid, lactic acid) or 5-fluorouracil or imiquimod (except as topical treatment to discrete BCCs) systemically or topically to the skin during the six months prior to entry.
c. Systemic chemotherapy within one year prior to screening. (Note: field therapy with topically applied treatments can me done as long as they are not applied within 5 cm of a treatment targeted tumor).
d. Known inhibitors of the HH signaling pathway (e.g., vismodegib patidegib, and sonidegib) topically or systemically within 6 months of entry into the study.

- The subject has uncontrolled systemic disease.
- The subject has clinically important history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis.

E.5 End points

E.5.1

Primary end point(s)

1. Primary efficacy endpoint is the decrease in tumor size defined as percent decrease in the sum of the greatest diameter of baseline treatment targeted SEBs
2. Change in GLI1 mRNA levels in drug-treated vs. vehicle-treated tumors after 6 weeks of treatment

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Week 26
2. after week 6

E.5.2

Secondary end point(s)

The secondary efficacy endpoints include:
- Change in tumor size defined as percent decrease in the sum of the greatest diameter of baseline treatment targeted SEBs.
- Change in tumor size defined as percent change in greatest diameter from Baseline of tumors located on the nose or periorbital area.
- Number of new SEBs on the face.
- Proportion of facial BCCs that at Baseline and/or Week 2 were less than 5 mm in greatest diameter but by Weeks 6, 10, 14, 18, 22, and 26 visit have become greater than 5 mm in greatest diameter.
- Proportion of baseline treatment targeted SEBs on the face that become less than 5 mm in greatest diameter and non-facial baseline treatment targeted SEBs that become less than 9 mm in greatest diameter.
• The reduction in the HH signaling pathway after treatment with patidegib gel 2% or 4% or vehicle applied twice daily for 6 weeks to treatment-targeted SEBs.

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 6, 10, 14, 18, 22, and 26.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-02-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-04-24

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