Study of the Efficacy and Safety of Somatropin in Japanese Participants With PWS

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, open label, multi cohort study to evaluate the efficacy and safety of somatropin in a cohort of Japanese participants with PWS.

Official Title
-----------------
A PHASE 3 MULTICENTER, OPEN LABEL, MULTI COHORT STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SOMATROPIN IN JAPANESE PARTICIPANTS WITH PRADER-WILLI SYNDROME (PWS)

Conditions
-----------------
Prader-Willi Syndrome

Intervention / Treatment
-----------------
* Biological: somatropin - GH naïve pediatric cohort
* Biological: somatropin - GH treated cohort
* Biological: somatropin - adult cohort


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants with documentation of genetically confirmed diagnosis of PWS. No plan to initiate a new treatment that may affect the body composition, such as gonadal hormone replacement therapy. Currently on appropriate diet and exercise programs and willing to continue throughout the study period at the discretion of the investigator. Participants, and if required by local/site regulations their parent(s)/legal guardian(s) must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Evidence of a personally signed and dated ICD (and written assent where applicable based on age and country regulation) indicating that the participant or a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study. Refer to Appendix 1 for the detailed process of obtaining consent. For inclusion of GH naïve pediatric cohort, participants must meet criteria 6 to 8: 18 years or younger. Naïve to GH treatment. Tanner stage 1 (for testes in males, for breasts in females). For inclusion of GH treated pediatric cohort, participants must meet criteria 9 and 10: Continued GH treatment for at least 2 years with stable dose for the last 6 months and being on GH at time of inclusion. The recent dose should be higher than 0.084 mg/kg/week. Participants who are about to complete GH treatment for his/her short stature (eg, due to meeting the treatment stopping criteria defined as a height SDS more than -2.5 for Japanese adult standards). For inclusion of adult cohort, participants must meet criteria 11 to 13: 18 years of chronological age or older at Day 1 visit. Off from GH treatment for at least 1 year. Serum IGF-I level within +2 SDS, adjusted for age and sex. Exclusion Criteria: Participants with uncontrolled diabetes at the discretion of the investigator. Participants with malignant tumors. Participants with severe obesity or serious respiratory impairment. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half- lives preceding the first dose of study intervention used in this study (whichever is longer). Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Ages Eligible for Study
-----------------
Minimum Age: 0 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: somatropin - GH naïve pediatric cohort<br>All participants will receive somatropin. | Biological: somatropin - GH naïve pediatric cohort<br>* somatropin 0.245 mg/kg/week<br>|
| Experimental: somatropin - GH treated pediatric cohort<br>All participants will receive somatropin | Biological: somatropin - GH treated cohort<br>* somatropin 0.084 mg/kg/week<br>|
| Experimental: somatropin - adult cohort<br>All participants will receive somatropin | Biological: somatropin - adult cohort<br>* somatropin 0.084 mg/kg/week<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Month 12 in lean body mass (%) measured by DEXA |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Month 12 in lean body mass (%) measured by BIA |  | 52 weeks | 
| Change from baseline to Month 12 in body fat (%) measured by DEXA |  | 52 weeks | 
| Change from baseline to Month 12 in adipose tissue distribution measured by abdominal CT |  | 52 weeks | 
| Change from baseline to Month 6 in lean body mass (%) measured by DEXA (adult cohort only) |  | 26 weeks | 
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) |  | Baseline up to 50 months | 
| Number of Participants With Treatment Emergent Treatment-Related Serious Adverse Events (SAEs) |  | Baseline up to 50 months | 
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities |  | Baseline up to 48 months | 
| Bone maturation |  | 52 weeks |