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PF-06651600 for the Treatment of Alopecia Areata (ALLEGRO-2b/3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03732807
Recruitment Status : Completed
First Posted : November 7, 2018
Results First Posted : February 24, 2022
Last Update Posted : February 24, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a global Phase 2b/3 study to evaluate the safety and effectiveness of an investigational study drug (called PF-06651600) in adults and adolescents (12 years and older) who have 50% or greater scalp hair loss. The study is placebo-controlled, meaning that some patients entering the study will not receive active study drug but will receive tablets with no active ingredients (a placebo). This is a dose-ranging study, investigating 5 different dosing regimens. It will be double-blinded, meaning that the sponsor, the study doctors, the staff, and the patients will not know whether a patient is on active study drug (or the dose) or placebo.

Condition or disease Intervention/treatment Phase
Alopecia Areata Drug: PF-06651600 Induction Dose Drug: PF-06651600 Maintenance Dose #1 Drug: PF-06651600 Maintenance Dose #2 Drug: PF-06651600 Maintenance Dose #3 Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 718 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 2B/3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF PF-06651600 IN ADULT AND ADOLESCENT ALOPECIA AREATA (AA) SUBJECTS WITH 50% OR GREATER SCALP HAIR LOSS
Actual Study Start Date : December 3, 2018
Actual Primary Completion Date : December 31, 2020
Actual Study Completion Date : June 24, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sequence A
Induction dose given once daily (QD) for 4 weeks followed by maintenance dose #1 given QD for 44 weeks
Drug: PF-06651600 Induction Dose
Oral tablets taken once daily (QD)

Drug: PF-06651600 Maintenance Dose #1
Oral tablets taken QD

Experimental: Sequence B
Induction dose given QD for 4 weeks followed by maintenance dose #2 given QD for 44 weeks
Drug: PF-06651600 Induction Dose
Oral tablets taken once daily (QD)

Drug: PF-06651600 Maintenance Dose #2
Oral tablets taken QD

Experimental: Sequence C
Maintenance dose #1 given QD for 48 weeks
Drug: PF-06651600 Maintenance Dose #1
Oral tablets taken QD

Experimental: Sequence D
Maintenance dose #2 given QD for 48 weeks
Drug: PF-06651600 Maintenance Dose #2
Oral tablets taken QD

Experimental: Sequence E
Maintenance dose #3 given QD for 48 weeks
Drug: PF-06651600 Maintenance Dose #3
Oral tablets taken QD

Experimental: Sequence F
Placebo given QD for 24 weeks followed by induction dose given QD for 4 weeks then maintenance dose #1 given QD for 20 weeks
Drug: PF-06651600 Induction Dose
Oral tablets taken once daily (QD)

Drug: PF-06651600 Maintenance Dose #1
Oral tablets taken QD

Drug: Placebo
Oral tablets taken QD

Experimental: Sequence G
Placebo given QD for 24 weeks followed by maintenance dose #1 given QD for 24 weeks
Drug: PF-06651600 Maintenance Dose #1
Oral tablets taken QD

Drug: Placebo
Oral tablets taken QD




Primary Outcome Measures :
  1. Percentage of Participants With an Absolute Severity of Alopecia Tool (SALT) Score of Less Than or Equal to 20 at Week 24 [ Time Frame: Week 24 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score less than or equal to (<=) 20 at week 24 were reported.


Secondary Outcome Measures :
  1. Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 10 at Week 24: Analysis 4 [ Time Frame: Week 24 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score <= 10 at week 24 were reported.

  2. Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 10 at Week 24: Analysis 1 [ Time Frame: Week 24 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score <= 10 at week 24 were reported.

  3. Percentage of Participants With Patient Global Impression of Change (PGI-C) Score of Moderately Improved or Greatly Improved at Week 24 [ Time Frame: Week 24 ]
    PGI-C is a self-administered questionnaire to evaluate the improvement or worsening of participant's AA as compared to the start of the study. PGI-C was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGI-C scores as follows: 1=greatly improved, 2=moderately improved, 3=slightly improved, 4=not changed, 5=slightly worsened, 6=moderately worsened and 7=greatly worsened.

  4. Exposure Response of PF-06651600 on Regrowth of Lost Hair Based on Absolute SALT Score of Less Than or Equal to 20 at Week 24: Maximum Effect (Emax) Model [ Time Frame: Week 24 ]
    The exposure response of Ritlecitinib (PF-06651600) on the regrowth of scalp hair was characterized using a Bayesian three-parameter hyperbolic Emax model for the SALT score <=20 at Week 24 with an additional term for effect of loading dose. In Emax exposure-response model the response function was the log odds of the percentage of participants with response based on SALT <=20 at Week 24, which was fit on the logistic scale and then back-transformed to percentage. The effect of loading dose is included as fixed factor in the model. The variable that represents loading dose has values of 1 for groups 200/50 mg once daily and 200/30 mg once daily and of 0 for the remaining groups. SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease.

  5. Exposure Response of PF-06651600 on Regrowth of Lost Hair Based on Absolute SALT Score of Less Than or Equal to 10 at Week 24: Maximum Effect (Emax) Model [ Time Frame: Week 24 ]
    The exposure response of Ritlecitinib (PF-06651600) on the regrowth of scalp hair was characterized using a Bayesian three-parameter hyperbolic Emax model for the SALT score <=10 at Week 24 with an additional term for effect of loading dose. In Emax exposure-response model the response function was the log odds of the percentage of participants with response based on SALT <=10 at Week 24, which was fit on the logistic scale and then back-transformed to percentage. The effect of loading dose is included as fixed factor in the model. The variable that represents loading dose has values of 1 for groups 200/50 mg once daily and 200/30 mg once daily and of 0 for the remaining groups. SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease.

  6. Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 20 at Week 4, 8, 12, 18, 28, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 28, 34, 40, and 48 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease.

  7. Percentage of Participants With an Absolute SALT Score of Less Than or Equal to 10 at Week 4, 8, 12, 18, 28, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 28, 34, 40, and 48 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. In this outcome measure, percentage of participants with SALT score <=10 were reported.

  8. Percentage of Participants With at Least 75% Improvement in SALT Score (SALT75) From Baseline at Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. A SALT 75 response was a 75% or greater reduction from baseline in SALT score.

  9. Change From Baseline in SALT Score at Week 4, 8, 12, 18, and 24 [ Time Frame: Baseline (Day 1), Week 4, 8, 12, 18, and 24 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. Baseline was defined as pre-dose on Day 1.

  10. Change From Baseline in SALT Score at Week 28, 34, 40, and 48 [ Time Frame: Baseline (Day 1), Week 28, 34, 40, and 48 ]
    SALT is a quantitative assessment of AA severity based on the scalp hair loss. The SALT score can vary from 0 (normal) to 100 (severe), with higher scores representing increased severity of disease. Baseline was defined as pre-dose on Day 1.

  11. Percentage of Participants With at Least a 2 Grade Improvement From Baseline or a Score of 3 in Eyebrow Assessment (EBA) Score (Among Participants Without Normal EBA at Baseline) at Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 ]
    EBA is a numeric rating scale developed to characterize eyebrow hair loss. The numeric rating scale ranges from 0 (none) to 3 (normal), where, 0= no eyebrow, 1=minimal eyebrow, 2=moderate eyebrow and 3= normal eyebrow, where higher scores represent less hair loss of eyebrows.

  12. Percentage of Participants With at Least a 2 Grade Improvement From Baseline or a Score of 3 in Eyelash Assessment (ELA) Score (Among Participants Without Normal ELA at Baseline) at Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 24, 28, 34, 40, and 48 ]
    ELA is a numeric rating scale developed to characterize eyelash hair loss. The numeric rating scale ranges from 0 (none) to 3 (normal), where, 0=no eyelash, 1=minimal eyelash, 2=moderate eyelash and 3=normal eyelash, where higher scores represent less hair loss of eyelash.

  13. Percentage of Participants With Patient Global Impression of Change (PGI-C) Score of Moderately Improved or Greatly Improved at Week 4, 8, 12, 18, 24, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 24, 34, 40, and 48 ]
    PGI-C is a self-administered questionnaire to evaluate the improvement or worsening of participant's AA as compared to the start of the study. PGI-C was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGI-C scores as follows: 1=greatly improved, 2=moderately improved, 3=slightly improved, 4=not changed, 5=slightly worsened, 6=moderately worsened and 7=greatly worsened.

  14. Change From Baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) Domain Scores at Week 4, 8, 12, 18, and 24: Emotional Symptoms and Activity Limitations [ Time Frame: Baseline (Day 1), Week 4, 8, 12, 18, and 24 ]
    AAPPO scale is 11-item self-administered questionnaire that measured hair loss, emotional symptoms, and activity limitations over past week. Items 1-4 assessed current hair loss, eyebrow loss, eyelash loss and body hair loss and were analyzed separately on scale of 0-4, with 0 ='no hair loss' and 4='complete hair loss'. Items 5-8 assessed emotional symptoms. Response choices on these items were scored from 0 ='never' to 4='always'. Items 9-11 assessed activity limitations. Response choices on these items were scored from 0='not at all' to 4='completely'. Change from baseline in AAPPO emotional symptoms sub score were calculated as mean of items 5-8 and ranged from 0(never) to 4(always), where higher scores indicated more emotional symptoms. Change from baseline in AAPPO activity limitations sub score was calculated as mean of items 9-11 and ranged from 0(not at all) to 4(completely), where higher scores indicated more activity limitations. Baseline was defined as pre-dose on Day 1.

  15. Change From Baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) Domain Scores at Week 34, 40, and 48: Emotional Symptoms and Activity Limitations [ Time Frame: Baseline (Day 1), Week 34, 40, and 48 ]
    AAPPO scale is 11-item self-administered questionnaire that measured hair loss, emotional symptoms, and activity limitations over past week. Items 1-4 assessed current hair loss, eyebrow loss, eyelash loss and body hair loss and were analyzed separately on scale of 0-4, with 0 ='no hair loss' and 4='complete hair loss'. Items 5-8 assessed emotional symptoms. Response choices on these items were scored from 0 ='never' to 4='always'. Items 9-11 assessed activity limitations. Response choices on these items were scored from 0='not at all' to 4='completely'. Change from baseline in AAPPO emotional symptoms sub score were calculated as mean of items 5-8 and ranged from 0(never) to 4(always), where higher scores indicated more emotional symptoms. Change from baseline in AAPPO activity limitations sub score was calculated as mean of items 9-11 and ranged from 0(not at all) to 4(completely), where higher scores indicated more activity limitations. Baseline was defined as pre-dose on Day 1.

  16. Percentage of Participants With Improvement From Baseline on Alopecia Areata Patient Priority Outcomes (AAPPO) Items 1-4 at Week 4, 8, 12, 18, 24, 34, 40, and 48 [ Time Frame: Week 4, 8, 12, 18, 24, 34, 40, and 48 ]
    AAPPO scale is a 11-item self-administered questionnaire that measured hair loss, emotional symptoms, and activity limitations over the past week. Items 1-4 were to assess the current hair loss, eyebrow loss, eyelash loss and body hair loss and were analyzed separately on a scale of 0-4, with 0 ='no hair loss' and 4='complete hair loss', where higher scores indicated more hair loss.


Other Outcome Measures:
  1. Change From Baseline in Depression Subscale Score of Hospital Anxiety and Depression Scale (HADS) at Weeks 4, 8, 12, and 24 [ Time Frame: Baseline (Day 1), Week 4, 8, 12, and 24 ]
    HADS is a validated 14-item PRO measure used to assess states of anxiety and depression over the past week. Items were rated on a 4-point severity scale. The HADS produces 2 scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states with established normal score cut-offs. The instrument have been validated for use by adolescents aged 12 and older. Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for depression subscale; higher score indicating greater severity of depression symptoms. Baseline was defined as pre-dose on Day 1.

  2. Change From Baseline in Depression Subscale Score of Hospital Anxiety and Depression Scale (HADS) at Week 48 [ Time Frame: Baseline (Day 1), Week 48 ]
    HADS is a validated 14-item PRO measure used to assess states of anxiety and depression over the past week. Items were rated on a 4-point severity scale. The HADS produces 2 scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states with established normal score cut-offs. The instrument have been validated for use by adolescents aged 12 and older. Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for depression subscale; higher score indicating greater severity of depression symptoms. Baseline was defined as pre-dose on Day 1.

  3. Change From Baseline in Anxiety Subscale Score of Hospital Anxiety and Depression Scale (HADS) at Weeks 4, 8, 12, and 24 [ Time Frame: Baseline (Day 1), Week 4, 8, 12, and 24 ]
    HADS is a validated 14-item PRO measure used to assess states of anxiety and depression over the past week. Items were rated on a 4-point severity scale. The HADS produces 2 scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states with established normal score cut-offs. The instrument have been validated for use by adolescents aged 12 and older. Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for anxiety subscale; higher score indicating greater severity of anxiety symptoms. Baseline was defined as pre-dose on Day 1.

  4. Change From Baseline in Anxiety Subscale Score of Hospital Anxiety and Depression Scale (HADS) at Week 48 [ Time Frame: Baseline (Day 1), Week 48 ]
    HADS is a validated 14-item PRO measure used to assess states of anxiety and depression over the past week. Items were rated on a 4-point severity scale. The HADS produces 2 scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states with established normal score cut-offs. The instrument have been validated for use by adolescents aged 12 and older. Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for anxiety subscale; higher score indicating greater severity of anxiety symptoms. Baseline was defined as pre-dose on Day 1.

  5. Percentage of Participants With a Baseline Score Indicative of Depression Achieving Normal Depression Subscale Score of HADS at Week 4, 8, 12, 24, and 48 [ Time Frame: Week 4, 8, 12, 24 and 48 ]
    HADS is a validated 14-item PRO measure used to assess states of anxiety and depression over the past week. Items were rated on a 4-point severity scale. The HADS produces 2 scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states with established normal score cut-offs. The instrument have been validated for use by adolescents aged 12 and older. Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for depression subscale; higher score indicating greater severity of depression symptoms.

  6. Percentage of Participants With a Baseline Score Indicative of Anxiety Achieving Normal Anxiety Subscale Score of HADS at Week 4, 8, 12, 24, and 48 [ Time Frame: Week 4, 8, 12, 24 and 48 ]
    HADS is a validated 14-item PRO measure used to assessed states of anxiety and depression over the past week. Items were rated on a 4-point severity scale. The HADS produces 2 scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states with established normal score cut-offs. The instrument have been validated for use by adolescents aged 12 and older. Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for anxiety subscale; higher score indicating greater severity of anxiety symptoms.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of alopecia areata with no other cause of hair loss
  • ≥50% hair loss of the scalp, including alopecia totalis and alopecia universalis, without evidence of terminal hair regrowth within 6 months
  • Current episode of hair loss ≤10 years

Exclusion Criteria:

  • Other types of alopecia or other diseases that can cause hair loss
  • Other scalp diseases that could interfere with assessment of hair loss/regrowth
  • Subjects with shaved heads must not enter the study until hair has grown back & is considered stable by the investigator
  • Any previous use of any Janus kinase (JAK) inhibitor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03732807


Locations
Show Show 155 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] April 14, 2021
Statistical Analysis Plan  [PDF] April 23, 2021

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03732807    
Other Study ID Numbers: B7981015
2018-001714-14 ( EudraCT Number )
ALLEGRO 2B/3 ( Other Identifier: Alias Study Number )
First Posted: November 7, 2018    Key Record Dates
Results First Posted: February 24, 2022
Last Update Posted: February 24, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Alopecia
Alopecia totalis
Alopecia universalis
Patchy hair loss
Diffuse hair loss
Hair loss
Hair disease
PF-06651600
Ritlecitinib
Additional relevant MeSH terms:
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Alopecia
Alopecia Areata
Hypotrichosis
Hair Diseases
Skin Diseases
Pathological Conditions, Anatomical