AcnePhase 2NCT01074502
Apremilast in the Treatment of Moderate to Severe Acne
A Phase 2 study testing apremilast in people with Acne, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Acne is a chronic inflammatory disease of the pilosebaceous unit that affects 80-90% of the population, especially teenagers, although adult acne is a significant problem for 3-6 % of adult men and 5-12% of adult women. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Acne
- What is being tested?
- apremilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2010to Oct 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Must understand and voluntarily sign an informed consent form.
- Must be male or female and aged 18-45 years of age, inclusive, at time of consent and be in general good health.
- Must be able to adhere to the study visit schedule and other protocol requirements
- Moderate to severe acne ( a 3 or 4 score in the RGA) of the face at Baseline.
- Subjects with 17-100 non-inflammatory lesions (open and closed comedones) and with 25-150 inflammatory lesions (papules and pustules) and 0-15 nodules (no larger than 1 cm each) and no cystic lesions.
- Must meet the following laboratory criteria:
Show all 18Show fewer
- Hemoglobin > 12 g/dL
- White blood cell (WBC) count ≥ 3000 /mL (≥ 3.0 X 109/L) and ≤ 14,000/mL (< 14 X 109/L)
- Platelets ≥ 100,000 /mL (≥ 100 X 109/L)
- Serum creatinine ≤ 1.5 mg/dL (or ≤ 133 μmol/L)
- Total bilirubin < 2.0 mg/dL
- Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) < 1.5x upper limit of normal (ULN)
- Negative ANA
- Negative cANCA
- Negative antiphospholipid antibodies
- Females of childbearing potential (FCBP)‡ must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception while on study medication: oral, injectable, or implantable hormonal contraceptives; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner while on study. A FCBP must agree to have pregnancy tests every 4 weeks while on study medication.
- Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in sexual activity with FCBP while on study medication and for 84 days after taking the last dose of study medication
- If a moisturizer or sunscreen is needed during the study, subjects must be willing to accept only acceptable products (non-comedogenic and without ingredients that may worsen or improve acne such as Cetaphil cleanser and Neutrogena oil-free moisturizer).
Who cannot join
- Inability to provide voluntary consent
- Use of any topical acne treatment (salicylic acid, benzoyl peroxide, retinol, antibiotics) 2 weeks prior to Baseline.
- Use of topical astringents or antimicrobial soaps for one week prior to Baseline.
- Use of any topical retinoid, systemic antibiotic or topical or systemic corticosteroids in the face 4 weeks prior to Baseline.
- Use of a systemic retinoid, such as isotretinoin, 6 months prior to Baseline
- Any confluent nodule, cyst and/or sinus tract present.
Show all 28Show fewer
- Any nodule larger than 10 mm.
- Subjects who are using medications that can exacerbate acne such as mega-doses of vitamin D, vitamin B2, B6, B12, haloperidol, halogens such as iodide and bromide, lithium, hydantoin and Phenobarbital). Multivitamins, iron supplements and folate are acceptable, but should be used consistently throughout the study.
- Subjects who have had a facial procedure (chemical or laser peel, blue light treatment, microdermabrasion, etc) within 4 weeks before enrollment or during the study.
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Subjects who abuse drugs or alcohol (drug screening not required).
- Pregnant, trying to become pregnant or breastfeeding.
- Use of estrogens, androgens or hormonal contraception or devices for less than 12 weeks prior to Baseline. Subjects are allowed to enroll as long as they do not expect to change dose, product, or discontinue use during the study.
- Systemic fungal infection
- History of active mycobacterial infection with any species (including Mycobacterium tuberculosis) within 3 years prior to screening visit. Subjects with Mycobacterium tuberculosis infection more than 3 years prior to screening visit are allowed if successful treatment was completed at least 3 years prior to randomization and is documented and available for verification.
- Mycobacterium tuberculosis infection as indicated by a positive Purified Protein Derivative [PPD] skin test (>15mm induration). Subjects with a positive PPD skin test are ineligible.
- History of incompletely treated Mycobacterium tuberculosis infection as indicated by
- Subject's medical records documenting incomplete treatment for Mycobacterium tuberculosis
- Subject's self-reported history of incomplete treatment for Mycobacterium tuberculosis
- History of recurrent bacterial infection (at least 3 major infections resulting in hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years)
- Clinically significant abnormality on the chest x-ray (CXR) at screening. Chest x-rays performed within 3 months prior to start of study drug are acceptable.
- Use of any investigational medication within 4 weeks prior to start of study drug or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer)
- Any clinically significant abnormality on 12-lead ECG at screening
- History of congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency [CVID])
- Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
- History of Human Immunodeficiency Virus (HIV) infection
- Antibodies to Hepatitis C at screening
- Malignancy or history of malignancy (except for treated [ie, cured] basal-cell skin carcinomas > 3 years prior to screening )
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of North Carolina
Chapel Hill, North Carolina, 27516
About this study
Official title: An Open-label, Single-arm Pilot Study of the Safety and Efficacy of an Oral PDE4-inhibitor Agent, Apremilast, in the Treatment of Moderate to Severe Acne
Acne is a chronic inflammatory disease of the pilosebaceous unit that affects 80-90% of the population, especially teenagers, although adult acne is a significant problem for 3-6 % of adult men and 5-12% of adult women. Although acne is not a life-threatening disease, it produces significant psychological disturbances and permanent skin scars.
A novel anti-inflammatory, not antibiotic drug may be an excellent alternative for the treatment of moderate to severe acne. Apremilast has been shown to inhibit the production of tumor necrosis factor (TNF)-alpha, IL-8 and neutrophil infiltration, all of which are elevated in inflammatory acne.
Our intention is to study Apremilast in the treatment of moderate to severe acne.
Read the detailed description
The hypothesized sequence of events in inflammatory acne starts with the formation of a microcomedone with accumulation of cornified keratinocytes within the follicle. Presence and/or proliferation of P.acnes induces the production of IL-1 alpha, tumor necrosis factor (TNF)- alpha, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Inflammation caused by CD4+ T cells causes a T-helper 1 cytokine response mediated by Toll-like receptors (TLR)-2 and TLR-4 whose expression is increased by P. acnes. Infiltration by neutrophils appears 72 hrs after, with possible disruption of the follicular wall and more inflammation. TNF-alpha liberated by keratinocytes stimulates the activation of pro-matrix metalloproteinase (MMP)-2 activity in the dermis with remodeling by fibroblasts with the consequence of possible scarring.
The usual treatment for moderate to severe inflammatory acne involves the use of long-term topical retinoids and antibiotics such as doxycycline or minocycline that had been showed to decrease the inflammatory response as well as decreasing the population of P. acnes. Since acne is a long term condition, several years of antibiotics are usually required. Recently, the problematic of antibiotic overuse has received great attention and concerns. Chronic antibiotic use has been implicated in increasing the risk of breast cancer and upper respiratory infections, and there is also a concern for antibiotic resistance. Recent recommendations by the Global Alliance to Improve Outcomes in Acne Group include the limitation for the use of oral antibiotics to a maximum of 3 months. So there is a need to find alternatives that does not include the use of oral antibiotics.
The only effective and available treatment for severe acne is isotretinoin which may have potential serious side effects. Lately also it has been implicated in the development of depression and suicidal ideations in the teenager population.
A novel anti-inflammatory, not antibiotic drug may be an excellent alternative for the treatment of moderate to severe acne. Apremilast has been shown to inhibit the production of tumor necrosis factor (TNF)-alpha, IL-8 and neutrophil infiltration, all of which are elevated in inflammatory acne. Preliminary data of the use of Apremilast in psoriasis makes us believe that this medication is safe for short-term use in acne patients.
Our intention is to study Apremilast in the treatment of moderate to severe acne.
- Conditions
- Acne
- Being tested
- apremilast
- Keywords
- acne
- Medical subject headings
- Acne Vulgaris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
apremilastDrug
apremilast 20 mgs orally twice a day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| apremilast | Experimental | apremilast 20 mgs twice a day for 12 weeks Receives: Drug: apremilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With a Success Rate (Based on the Researcher's Global Assessment (RGA) Sum of Clear (0) or Almost Clear (1))
RGA measures the severity of acne. The scale goes from 0-4. 0 will be better and 4 will be worse. Scores can only be whole numbers (0,1,2,3,4)ordinal.
Measured: Baseline to 16 weeks
Percentage of Patients With a Minimum 2-grade Improvement in the Researcher Global Assessment (RGA) From Baseline to Week 12.
RGA measures the severity of acne. The scale goes from 0 (better)to 4 (worse). Score can only be whole numbers, ordinal.
Measured: Baseline to 12 weeks
Mean Percentage Change From Baseline in Individual Lesion Counts (Total, Inflammatory, Non-inflammatory) at Week 12
Measured: Baseline to 12 weeks
Percentage of Patients Achieving a Clear or Almost Clear PGA at 16 Weeks
Measured: Baseline to 16 weeks
Secondary outcomes (2)
The Absolute Change in Lesion Counts (Total, Inflammatory, Non-inflammatory) From Baseline to Week 12
Measured: Baseline to12 weeks
Safety of Apremilast 20 Mgs BID for 12 Weeks Will be Assessed by Evaluating Adverse Events (AEs), Vital Signs, Laboratory Evaluations and Withdrawals From the Study
Number of participants with adverse events
Measured: Baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionJul 2010
- Study completionOct 2010
Why it stopped: lack of funding due to Celgene administrative decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AcneStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene
- Responsible party
- Principal investigator, Aida Lugo-Somolinos, MD, University of North Carolina, Chapel Hill
- Investigators
- Aida Lugo-Somolinos, MD, Principal investigator, UNC Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01074502
- Sponsor's protocol ID
- CELG0001
- Status last verified
- Feb 2017
- First submitted
- 22 Feb 2010
- Last updated
- 13 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm Pilot Study of the Safety and Efficacy of an Oral PDE4-inhibitor Agent, Apremilast, in the Treatment of Moderate to Severe Acne
- ClinicalTrials.gov ID
- NCT01074502
- Acronym / sponsor ID
- CELG0001
- Conditions
- Acne
- Keywords
- acne
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of funding due to Celgene administrative decision
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Celgene
- Study start
- Feb 2010
- Primary completion
- Jul 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 24 Feb 2010 (estimated)
- Results
- Posted 12 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acne is a chronic inflammatory disease of the pilosebaceous unit that affects 80-90% of the population, especially teenagers, although adult acne is a significant problem for 3-6 % of adult men and 5-12% of adult women. Although acne is not a life-threatening disease, it produces significant psychological disturbances and permanent skin scars.
A novel anti-inflammatory, not antibiotic drug may be an excellent alternative for the treatment of moderate to severe acne. Apremilast has been shown to inhibit the production of tumor necrosis factor (TNF)-alpha, IL-8 and neutrophil infiltration, all of which are elevated in inflammatory acne.
Our intention is to study Apremilast in the treatment of moderate to severe acne.
Detailed description
The hypothesized sequence of events in inflammatory acne starts with the formation of a microcomedone with accumulation of cornified keratinocytes within the follicle. Presence and/or proliferation of P.acnes induces the production of IL-1 alpha, tumor necrosis factor (TNF)- alpha, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Inflammation caused by CD4+ T cells causes a T-helper 1 cytokine response mediated by Toll-like receptors (TLR)-2 and TLR-4 whose expression is increased by P. acnes. Infiltration by neutrophils appears 72 hrs after, with possible disruption of the follicular wall and more inflammation. TNF-alpha liberated by keratinocytes stimulates the activation of pro-matrix metalloproteinase (MMP)-2 activity in the dermis with remodeling by fibroblasts with the consequence of possible scarring.
The usual treatment for moderate to severe inflammatory acne involves the use of long-term topical retinoids and antibiotics such as doxycycline or minocycline that had been showed to decrease the inflammatory response as well as decreasing the population of P. acnes. Since acne is a long term condition, several years of antibiotics are usually required. Recently, the problematic of antibiotic overuse has received great attention and concerns. Chronic antibiotic use has been implicated in increasing the risk of breast cancer and upper respiratory infections, and there is also a concern for antibiotic resistance. Recent recommendations by the Global Alliance to Improve Outcomes in Acne Group include the limitation for the use of oral antibiotics to a maximum of 3 months. So there is a need to find alternatives that does not include the use of oral antibiotics.
The only effective and available treatment for severe acne is isotretinoin which may have potential serious side effects. Lately also it has been implicated in the development of depression and suicidal ideations in the teenager population.
A novel anti-inflammatory, not antibiotic drug may be an excellent alternative for the treatment of moderate to severe acne. Apremilast has been shown to inhibit the production of tumor necrosis factor (TNF)-alpha, IL-8 and neutrophil infiltration, all of which are elevated in inflammatory acne. Preliminary data of the use of Apremilast in psoriasis makes us believe that this medication is safe for short-term use in acne patients.
Our intention is to study Apremilast in the treatment of moderate to severe acne.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| apremilast | Experimental | Drug: apremilastapremilast 20 mgs twice a day for 12 weeks |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Must understand and voluntarily sign an informed consent form.
- Must be male or female and aged 18-45 years of age, inclusive, at time of consent and be in general good health.
- Must be able to adhere to the study visit schedule and other protocol requirements
- Moderate to severe acne ( a 3 or 4 score in the RGA) of the face at Baseline.
- Subjects with 17-100 non-inflammatory lesions (open and closed comedones) and with 25-150 inflammatory lesions (papules and pustules) and 0-15 nodules (no larger than 1 cm each) and no cystic lesions.
Key exclusion criteria (28 listed)
- Inability to provide voluntary consent
- Use of any topical acne treatment (salicylic acid, benzoyl peroxide, retinol, antibiotics) 2 weeks prior to Baseline.
- Use of topical astringents or antimicrobial soaps for one week prior to Baseline.
- Use of any topical retinoid, systemic antibiotic or topical or systemic corticosteroids in the face 4 weeks prior to Baseline.
- Use of a systemic retinoid, such as isotretinoin, 6 months prior to Baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| apremilastapremilast 20 mgs orally twice a day for 12 weeks | Drug | apremilast |
Primary outcome
Percentage of Patients With a Success Rate (Based on the Researcher's Global Assessment (RGA) Sum of Clear (0) or Almost Clear (1))
Time frame: Baseline to 16 weeks
RGA measures the severity of acne. The scale goes from 0-4. 0 will be better and 4 will be worse. Scores can only be whole numbers (0,1,2,3,4)ordinal.
Percentage of Patients With a Minimum 2-grade Improvement in the Researcher Global Assessment (RGA) From Baseline to Week 12.
Time frame: Baseline to 12 weeks
RGA measures the severity of acne. The scale goes from 0 (better)to 4 (worse). Score can only be whole numbers, ordinal.
Mean Percentage Change From Baseline in Individual Lesion Counts (Total, Inflammatory, Non-inflammatory) at Week 12
Time frame: Baseline to 12 weeks
Percentage of Patients Achieving a Clear or Almost Clear PGA at 16 Weeks
Time frame: Baseline to 16 weeks
2 secondary outcomes
The Absolute Change in Lesion Counts (Total, Inflammatory, Non-inflammatory) From Baseline to Week 12
Time frame: Baseline to12 weeks
Safety of Apremilast 20 Mgs BID for 12 Weeks Will be Assessed by Evaluating Adverse Events (AEs), Vital Signs, Laboratory Evaluations and Withdrawals From the Study
Time frame: Baseline to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aida Lugo-Somolinos, MD principal investigator
UNC Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing apremilast in people with Acne, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With a Success Rate (Based on the Researcher's Global Assessment (RGA) Sum of Clear (0) or Almost Clear (1)) (time frame: Baseline to 16 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2017.