Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (NCT NCT03905330)

Last Updated: 2023-12-11

Results Overview

The primary efficacy endpoint is the mean change in the average morning ItchRO(Obs) severity score between baseline and Weeks 15-26, using 4-week average morning ItchRO(Obs) severity scores (Mixed Model Repeated Measures). The baseline average morning ItchRO(Obs) severity score is defined as the 4-week average morning ItchRO(Obs) severity score prior to the first dose of the study medication. ItchRo(Obs) Severity Score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

93 participants

Primary outcome timeframe

MMRM model was used with inputs of the average changes from baseline (BL) to Weeks 1-6, 7-10, 11-14, 15-18, 19-22, 23-26, and other covariates. The average change from BL over Weeks 15-26 is calculated in the model and presented as a single number.

Results posted on

2023-12-11

Participant Flow

A total of 93 participants were enrolled at 29 sites in 16 countries (Argentina, Austria, Belgium, Brazil, Canada, Colombia, France, Germany, Italy, Lebanon, Mexico, Poland, Singapore, Turkey, United Kingdom, and United States).

The screening period starts when informed consent (or assent as applicable) is signed. The duration of the screening period is up to 6 weeks during which all procedures listed for the screening visit must be completed. A total of 125 patients were screened for the study. 32 of these patients were screen failures.

Participant milestones

Participant milestones
Measure	Maralixibat Maralixibat up to 600 mcg/kg twice daily	Placebo Corresponding placebo
Overall Study STARTED	47	46
Overall Study Dosed 150 ug/kg BID	47	0
Overall Study Dosed 300 ug/kg BID	46	0
Overall Study Dosed 450 ug/kg BID	45	0
Overall Study Dosed 600 ug/kg BID	45	0
Overall Study COMPLETED	44	42
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The primary cohort and PFIC cohort are not mutually exclusive. Specifically, the primary cohort is fully contained in the PFIC cohort. The total population (n=93) consists of the primary cohort (n=31), the additional subjects in the PFIC cohort (n=33) and an additional 29 subjects for whom we did not run any primary or secondary efficacy analyses.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: MMRM model was used with inputs of the average changes from baseline (BL) to Weeks 1-6, 7-10, 11-14, 15-18, 19-22, 23-26, and other covariates. The average change from BL over Weeks 15-26 is calculated in the model and presented as a single number.

Population: Primary Cohort, defined as participants with genetic testing results consistent with biallelic disease causing variation in ABCB11 (PFIC2, also referred to as BSEP deficiency), based on standard-of-care genotyping, excluding those PFIC2 participants predicted to have complete absence of BSEP function (PFIC2 participants with heterozygosis, biliary diversion, having low or fluctuating sBA levels).

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=14 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=17 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Mean Change in the Average Morning ItchRO(Obs) Severity Score in the Primary Cohort	-1.718 Score on a scale Interval -2.272 to -1.163	-0.628 Score on a scale Interval -1.136 to -0.121

SECONDARY outcome

Timeframe: Baseline and average of Weeks 18, 22 and 26

Mean change in total sBA level between baseline and average of Weeks 18, 22 and 26.

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=12 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=17 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Mean Change in Total sBA Level in the Primary Cohort.	-175.536 μmol/L Interval -256.716 to -94.356	11.187 μmol/L Interval -58.073 to 80.446

SECONDARY outcome

Timeframe: Between Baseline and Week 15 through Week 26

Population: Primary cohort plus PFIC1, PFIC3, PFIC4, PFIC6.

Mean change in the average morning ItchRO(Obs) severity score between baseline and Week 15 through Week 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6). ItchRo(Obs) Severity Score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=33 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=31 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Mean Change in the Average Morning ItchRO(Obs) Severity Score in Participants With PFIC (PFIC1, Nt-PFIC2, PFIC3, PFIC4 and PFIC6)	-1.811 score on a scale Interval -2.178 to -1.444	-0.610 score on a scale Interval -1.0 to -0.221

SECONDARY outcome

Timeframe: Between Baseline and average of Weeks 18, 22 and 26

Population: Primary cohort plus PFIC1, PFIC3, PFIC4 and PFIC6.

Mean change in total sBA level between baseline and average of Weeks 18, 22, and 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=33 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=31 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Mean Change in Total sBA Level in Participants With PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)	-157.489 μmol/L Interval -200.276 to -114.703	2.913 μmol/L Interval -42.32 to 48.146

SECONDARY outcome

Timeframe: Week 15 to Week 26 using the average value from the three 4-week periods (Weeks 15-18, 19-22 and 23-26)

Proportion of ItchRO(Obs) responders from Week 15 to Week 26 in participants with PFIC2 using the average value from the three 4-week periods (Weeks 15-18, 19-22 and 23-26). The number in the Subject Analysis Set refers to the number of responders. ItchRO responders are defined as a subject having a 4-week average morning ItchRO(Obs) severity change from baseline of ≤-1.0 or an average severity score of ≤1.0.

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=14 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=17 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Proportion of ItchRO(Obs) Responders in the Primary Cohort	8 Number of responders	4 Number of responders

SECONDARY outcome

Timeframe: Average value from Weeks 18, 22 and 26

Proportion of sBA responders from Week 18 to Week 26 in participants with PFIC2, using the average value from Weeks 18, 22 and 26 values. The number in the Subject Analysis Set refers to the number of responders. sBA responders are defined as a subject having an average sBA level of \<102 umol/L (applies only if baseline sBA level was ≥102 umol/L), OR a ≤-75% average percent change from baseline.

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=14 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=17 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Proportion of sBA Responders in the Primary Cohort	5 Number of responders	1 Number of responders

SECONDARY outcome

Timeframe: From Week 15 to Week 26

Population: Primary cohort plus PFIC1, PFIC3, PFIC4 and PFIC6.

Proportion of ItchRO(Obs) responders from Week 15 to Week 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6). The number in the Subject Analysis Set refers to the number of responders. ItchRO responders are defined as a subject having a 4-week average morning ItchRO(Obs) severity change from baseline of ≤-1.0 OR an average severity score of ≤1.0.

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=33 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=31 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Proportion of ItchRO(Obs) Responders PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)	21 Number of responders	8 Number of responders

SECONDARY outcome

Timeframe: Week 18 to Week 26

Population: Primary cohort plus PFIC1, PFIC3, PFIC4 and PFIC6.

Proportion of sBA responders from Week 18 to Week 26 in participants with PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6). The number in the Subject Analysis Set refers to the number of responders. sBA responders are defined as a subject having an average sBA level of \<102 umol/L (applies only if baseline sBA level was ≥102 umol/L), or a ≤-75% average percent change from baseline.

Outcome measures

Outcome measures
Measure	Primary Cohort Maralixibat n=33 Participants Participants received Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks. Maralixibat: Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.	Primary Cohort Placebo n=31 Participants Participants received placebo matched to maralixibat oral solution twice daily for 26 weeks. Placebo: Placebo matching to maralixibat orally twice daily for 26 weeks.
Proportion of sBA Responders PFIC (PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6)	15 Number of responders	2 Number of responders

Adverse Events

Maralixibat

Serious events: 5 serious events

Other events: 47 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Maralixibat n=47 participants at risk All participants who received at least 1 dose of maralixibat	Placebo n=46 participants at risk All participants who received at least 1 dose of placebo
Injury, poisoning and procedural complications Accidental exposure to product	0.00% 0/47 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	2.2% 1/46 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Investigations Blood bilirubin increased	2.1% 1/47 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	0.00% 0/46 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Hepatobiliary disorders Cholestasis	2.1% 1/47 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	0.00% 0/46 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/47 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	2.2% 1/46 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Gastrointestinal disorders Constipation	2.1% 1/47 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	0.00% 0/46 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Gastroenteritis viral	0.00% 0/47 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	2.2% 1/46 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Respiratory, thoracic and mediastinal disorders Idiopathic pneumonia syndrome	2.1% 1/47 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	0.00% 0/46 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Nervous system disorders Seizure	0.00% 0/47 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	2.2% 1/46 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Urinary tract infection	4.3% 2/47 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	0.00% 0/46 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Metabolism and nutrition disorders Vitamin K deficiency	0.00% 0/47 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	2.2% 1/46 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.

Other adverse events

Additional Information

Mirum Clinical Trials

Mirum Pharmaceuticals

Phone: 650-667-4085

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Maralixibat n=47 participants at risk All participants who received at least 1 dose of maralixibat	Placebo n=46 participants at risk All participants who received at least 1 dose of placebo
Investigations Blood bilirubin increased	14.9% 7/47 • Number of events 7 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	8.7% 4/46 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Investigations Alanine aminotransferase increased	12.8% 6/47 • Number of events 7 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	6.5% 3/46 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Investigations Vitamin E decreased	8.5% 4/47 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	6.5% 3/46 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Investigations Vitamin D decreased	8.5% 4/47 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	4.3% 2/46 • Number of events 2 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Investigations International normalised ratio increased	2.1% 1/47 • Number of events 1 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	8.7% 4/46 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
General disorders Pyrexia	36.2% 17/47 • Number of events 19 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	28.3% 13/46 • Number of events 20 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Gastrointestinal disorders Diarrhoea	57.4% 27/47 • Number of events 51 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	19.6% 9/46 • Number of events 16 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Gastrointestinal disorders Abdominal pain	21.3% 10/47 • Number of events 16 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	6.5% 3/46 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Gastrointestinal disorders Vomiting	6.4% 3/47 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	10.9% 5/46 • Number of events 7 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Gastrointestinal disorders Abdominal pain upper	4.3% 2/47 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	8.7% 4/46 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Gastrointestinal disorders Constipation	8.5% 4/47 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	4.3% 2/46 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/47 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	10.9% 5/46 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	17.0% 8/47 • Number of events 11 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	10.9% 5/46 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Respiratory, thoracic and mediastinal disorders Cough	14.9% 7/47 • Number of events 9 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	10.9% 5/46 • Number of events 8 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Skin and subcutaneous tissue disorders Pruritus	10.6% 5/47 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	17.4% 8/46 • Number of events 10 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Upper respiratory tract infection	6.4% 3/47 • Number of events 6 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	13.0% 6/46 • Number of events 10 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Influenza	12.8% 6/47 • Number of events 9 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	4.3% 2/46 • Number of events 2 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Coronavirus infection	6.4% 3/47 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	8.7% 4/46 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Nasopharyngitis	10.6% 5/47 • Number of events 8 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	4.3% 2/46 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Infections and infestations Gastroenteritis	6.4% 3/47 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	4.3% 2/46 • Number of events 2 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Metabolism and nutrition disorders Vitamin D deficiency	8.5% 4/47 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	8.7% 4/46 • Number of events 5 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.
Metabolism and nutrition disorders Vitamin E deficiency	6.4% 3/47 • Number of events 3 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.	8.7% 4/46 • Number of events 4 • Baseline to end of treatment (EOT); where EOT can be up to 26 weeks if participant did not early terminate. The Study Protocol did not require to collect Adverse Events by dose level.