AZP01-CLI-003

Millendo Therapeutics

8 rue Berjon, Lyon, France, 69009

Clinical Trial Information, Millendo Therapeutics SAS, +33 4 72 18 94 28, harisseh@millendo.com

Clinical Trial Information, Millendo Therapeutics SAS, +33 4 72 18 94 28, harisseh@millendo.com

No

No

No

Final

08 Sep 2020

Yes

25 May 2020

Yes

25 May 2020

Yes

Core Period Phase 2b To demonstrate the efficacy of a 3-month treatment with livoletide as compared to placebo for reducing caregiver-observed food-related behavior as assessed by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Note: the results presented here are only from the Phase 2b Core Period part of the study which was completed before the study was terminated. Phase 3 To demonstrate the efficacy of a 6-month treatment with livoletide as compared to placebo for reducing caregiver-observed food-related behavior as assessed by HQ-CT. Note: Phase 3 was not started because the clinical trial was terminated early by the Sponsor during the Phase 2b part of the study.

The Investigator was responsible for ensuring that patients did not undergo any study-related examination or activity before giving informed consent. The patient must have given written consent after the receipt of detailed information regarding the study. The verbal explanation covered all the elements specified in the written information provided to the patient. If the written informed consent was provided by the legal guardian because the patient was unable to do so, a written or verbal assent from the patient must have also been obtained. The Investigators have informed the patient of the aims, methods, anticipated benefits, and potential hazards of the study, including any discomfort it may entail. The patient must have been given every opportunity to clarify any points he/she did not understand and must have been provided with more information if requested. At the end of the interview, the patient may have been given time to reflect and could request more time if was needed. The patient and/or legal guardian have been required to sign and date the informed consent form. After completion, informed consent forms were kept and archived by the Investigator in the Investigator study file. It was to be emphasized to the patient that he or she was at liberty to either discontinue study drug and/or withdraw consent to participate at any time, without penalty or loss of benefits to which he or she was otherwise entitled. Patients who refused to give or withdraw written informed consent may have not been included or continued in this study, but this did not affect their subsequent care. In addition, a safety data review was performed at a regular basis during the trial by an external Data Monitoring Committee (DMC) operating independently of the Sponsor to make recommendations for the conduct of the study based on safety data. The DMC did operate under the rules of an approved charter defining the roles and responsibilities of its members.

25 Mar 2019

No

Yes

Netherlands: 8

Spain: 30

United Kingdom: 3

Belgium: 5

France: 34

Italy: 5

Australia: 7

United States: 66

158

82

0

0

0

0

26

41

91

0

0

Treatment Period: Phase 2b Core Period (overall period)

Randomised - controlled

Yes

Livoletide

Injection

Subcutaneous use

The study drug will be administered subcutaneously as a single injection under a full skin fold of the anterior abdominal region, at rotating sites, every day during the treatment period.

Livoletide

Injection

Subcutaneous use

The study drug will be administered subcutaneously as a single injection under a full skin fold of the anterior abdominal region, at rotating sites, every day during the treatment period.

Placebo

Injection

Subcutaneous use

Placebo will be administered subcutaneously as a single injection under a full skin fold of the anterior abdominal region, at rotating sites, every day during the treatment period.

Low-dose livoletide

High-dose livoletide

Placebo

Phase 2b Core Period, Eight to 65 years of age

All analyses were performed for the eight to 65 years of age cohort only. Only one patient < eight years of age was evaluated in the Phase 2b Core Period. This patient was randomized into the placebo group. This patient is not included the analyses. The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.

Low-dose livoletide

High-dose livoletide

Placebo

Phase 2b Core Period, Eight to 65 years of age

All analyses were performed for the eight to 65 years of age cohort only. Only one patient < eight years of age was evaluated in the Phase 2b Core Period. This patient was randomized into the placebo group. This patient is not included the analyses. The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.

HQ-CT is a 9-item caregiver-reported measure of behaviors commonly associated with hyperphagia in patients with Prader–Willi Syndrome. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.

Primary

Change from baseline to month 3

High-dose livoletide v Placebo v Low-dose livoletide

158

Pre-specified

The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007. Overweight/obese patients were defined as follows: o patients ≥18 years of age: BMI ≥27 kg/m2 o patients 4-17 years of age: BMI ≥90th percentile for the same age and sex

Secondary

Change from baseline to month 3

Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings. Overweight/obese patients were defined as follows: o patients ≥18 years of age: BMI ≥27 kg/m2 o patients 4-17 years of age: BMI ≥90th percentile for the same age and sex

Secondary

Change from baseline to month 3

Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible. Overweight/obese patients were defined as follows: o patients ≥18 years of age: BMI ≥27 kg/m2 o patients 4-17 years of age: BMI ≥90th percentile for the same age and sex

Secondary

Change from baseline to month 3

The analysis of Treatment-emergent adverse events (TEAEs) was done starting first dose of study drug and through 30 days after the end of the treatment period

AEs were experienced by 34 (65.4%) patients in the livoletide 60 µg/mL group, 35 (67.3%) patients in the livoletide 120 µg/mL group, and 37 (68.5%) patients in the placebo group. TEAEs were experienced by 34 (65.4%) patients in the livoletide 60 µg/mL, 34 (65.4%) patients in the livoletide 120 µg/mL, and 34 (63.0%) patients in placebo group.

22.0

Low-dose livoletide

High-dose livoletide

Placebo